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Wang Y, Barmin R, Mottaghy FM, Kiessling F, Lammers T, Pallares RM. Nanoparticles in nuclear medicine: From diagnostics to therapeutics. J Control Release 2025; 383:113815. [PMID: 40319914 DOI: 10.1016/j.jconrel.2025.113815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 04/13/2025] [Accepted: 05/02/2025] [Indexed: 05/07/2025]
Abstract
The use of nanoparticles in nuclear medicine is paradoxical. While several nanoformulations, such as 99mTc colloids, have been used for diagnosis for decades, only a few new radionanomedicines have been able to reach the market, despite extensive preclinical efforts. This contradiction is dictated by the unique features of nanoparticles, such as (potential) prolonged circulation times, slow compartment exchanges, and large accumulations in the mononuclear phagocyte system, which allow for certain specific applications while preventing others. In this review, we discuss the development and clinical application of radiolabeled nanoparticles as imaging agents for disease diagnosis and patient stratification, as well as their promise and potential to be used as next-generation formulations to improve the efficacy of radiotherapy.
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Affiliation(s)
- Ying Wang
- Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, Aachen 52074, Germany
| | - Roman Barmin
- Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, Aachen 52074, Germany
| | - Felix M Mottaghy
- Department of Nuclear Medicine, RWTH Aachen University Hospital, Aachen 52074, Germany; Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+), Maastricht, the Netherlands
| | - Fabian Kiessling
- Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, Aachen 52074, Germany
| | - Twan Lammers
- Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, Aachen 52074, Germany
| | - Roger M Pallares
- Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, Aachen 52074, Germany.
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Yang F, Lei B, Zhou Z, Song TA, Balaji V, Dutta J. AI in SPECT Imaging: Opportunities and Challenges. Semin Nucl Med 2025; 55:294-312. [PMID: 40189986 PMCID: PMC12004277 DOI: 10.1053/j.semnuclmed.2025.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2025] [Revised: 03/25/2025] [Accepted: 03/26/2025] [Indexed: 04/18/2025]
Abstract
SPECT is a widely used imaging modality in nuclear medicine which provides essential functional insights into cardiovascular, neurological, and oncological diseases. However, SPECT imaging suffers from limited quantitative accuracy due to low spatial resolution and high noise levels, posing significant challenges for precise diagnosis, disease monitoring, and treatment planning. Recent advances in artificial intelligence (AI), in particular deep learning-based techniques such as convolutional neural networks (CNNs), generative adversarial networks (GANs), and transformers, have led to substantial improvements in SPECT image reconstruction, enhancement, attenuation correction, segmentation, disease classification, and multimodal fusion. These AI approaches have enabled more accurate extraction of functional and anatomical information, improved quantitative analysis, and facilitated the integration of SPECT with other imaging modalities to enhance clinical decision-making. This review provides a comprehensive overview of AI-driven developments in SPECT imaging, highlighting progress in both supervised and unsupervised learning approaches, innovations in image synthesis and cross-modality learning, and the potential of self-supervised and contrastive learning strategies for improving model robustness. Additionally, we discuss key challenges, including data heterogeneity, model interpretability, and computational complexity, which continue to limit the clinical adoption of AI methods. The need for standardized evaluation metrics, large-scale multimodal datasets, and clinically validated AI models remains a crucial factor in ensuring the reliability and generalizability of AI approaches. Future research directions include the exploration of foundation models and large language models for knowledge-driven image analysis, as well as the development of more adaptive and personalized AI frameworks tailored for nuclear imaging applications.
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Affiliation(s)
- Fan Yang
- Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, MA
| | - Bowen Lei
- Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, MA
| | - Ziyuan Zhou
- Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, MA
| | - Tzu-An Song
- Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, MA
| | - Vibha Balaji
- Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, MA
| | - Joyita Dutta
- Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, MA.
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Moonen CT, Kilroy JP, Klibanov AL. Focused Ultrasound: Noninvasive Image-Guided Therapy. Invest Radiol 2025; 60:205-219. [PMID: 39163359 PMCID: PMC11801465 DOI: 10.1097/rli.0000000000001116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 06/27/2024] [Indexed: 08/22/2024]
Abstract
ABSTRACT Invasive open surgery used to be compulsory to access tumor mass to perform excision or resection. Development of minimally invasive laparoscopic procedures followed, as well as catheter-based approaches, such as stenting, endovascular surgery, chemoembolization, brachytherapy, which minimize side effects and reduce the risks to patients. Completely noninvasive procedures bring further benefits in terms of reducing risk, procedure time, recovery time, potential of infection, or other side effects. Focusing ultrasound waves from the outside of the body specifically at the disease site has proven to be a safe noninvasive approach to localized ablative hyperthermia, mechanical ablation, and targeted drug delivery. Focused ultrasound as a medical intervention was proposed decades ago, but it only became feasible to plan, guide, monitor, and control the treatment procedures with advanced radiological imaging capabilities. The purpose of this review is to describe the imaging capabilities and approaches to perform these tasks, with the emphasis on magnetic resonance imaging and ultrasound. Some procedures already are in clinical practice, with more at the clinical trial stage. Imaging is fully integrated in the workflow and includes the following: (1) planning, with definition of the target regions and adjacent organs at risk; (2) real-time treatment monitoring via thermometry imaging, cavitation feedback, and motion control, to assure targeting and safety to adjacent normal tissues; and (3) evaluation of treatment efficacy, via assessment of ablation and physiological parameters, such as blood supply. This review also focuses on sonosensitive microparticles and nanoparticles, such as microbubbles injected in the bloodstream. They enable ultrasound energy deposition down to the microvascular level, induce vascular inflammation and shutdown, accelerate clot dissolution, and perform targeted drug delivery interventions, including focal gene delivery. Especially exciting is the ability to perform noninvasive drug delivery via opening of the blood-brain barrier at the desired areas within the brain. Overall, focused ultrasound under image guidance is rapidly developing, to become a choice noninvasive interventional radiology tool to treat disease and cure patients.
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Zhang S, Wang X, Gao X, Chen X, Li L, Li G, Liu C, Miao Y, Wang R, Hu K. Radiopharmaceuticals and their applications in medicine. Signal Transduct Target Ther 2025; 10:1. [PMID: 39747850 PMCID: PMC11697352 DOI: 10.1038/s41392-024-02041-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 08/30/2024] [Accepted: 10/28/2024] [Indexed: 01/04/2025] Open
Abstract
Radiopharmaceuticals involve the local delivery of radionuclides to targeted lesions for the diagnosis and treatment of multiple diseases. Radiopharmaceutical therapy, which directly causes systematic and irreparable damage to targeted cells, has attracted increasing attention in the treatment of refractory diseases that are not sensitive to current therapies. As the Food and Drug Administration (FDA) approvals of [177Lu]Lu-DOTA-TATE, [177Lu]Lu-PSMA-617 and their complementary diagnostic agents, namely, [68Ga]Ga-DOTA-TATE and [68Ga]Ga-PSMA-11, targeted radiopharmaceutical-based theranostics (radiotheranostics) are being increasingly implemented in clinical practice in oncology, which lead to a new era of radiopharmaceuticals. The new generation of radiopharmaceuticals utilizes a targeting vector to achieve the accurate delivery of radionuclides to lesions and avoid off-target deposition, making it possible to improve the efficiency and biosafety of tumour diagnosis and therapy. Numerous studies have focused on developing novel radiopharmaceuticals targeting a broader range of disease targets, demonstrating remarkable in vivo performance. These include high tumor uptake, prolonged retention time, and favorable pharmacokinetic properties that align with clinical standards. While radiotheranostics have been widely applied in tumor diagnosis and therapy, their applications are now expanding to neurodegenerative diseases, cardiovascular diseases, and inflammation. Furthermore, radiotheranostic-empowered precision medicine is revolutionizing the cancer treatment paradigm. Diagnostic radiopharmaceuticals play a pivotal role in patient stratification and treatment planning, leading to improved therapeutic outcomes in targeted radionuclide therapy. This review offers a comprehensive overview of the evolution of radiopharmaceuticals, including both FDA-approved and clinically investigated agents, and explores the mechanisms of cell death induced by radiopharmaceuticals. It emphasizes the significance and future prospects of theranostic-based radiopharmaceuticals in advancing precision medicine.
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Grants
- 82372002 National Natural Science Foundation of China (National Science Foundation of China)
- 0104002 Beijing Nova Program
- L248087; L234044 Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation)
- Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences (No. 2022-RC350-04), the CAMS Innovation Fund for Medical Sciences (Nos. 2021-I2M-1-026, 2022-I2M-2-002-2, and 2021-I2M-3-001), the National Key Research and Development Program of China (No. 2022YFE0111700),the Fundamental Research Funds for the Central Universities (Nos. 3332023044 and 3332023151), the CIRP Open Fund of Radiation Protection Laboratories (No. ZHYLYB2021005), and the China National Nuclear Corporation Young Talent Program.
- Fundamental Research Funds for the Central Universities,Nos. 3332023044
- Fundamental Research Funds for the Central Universities,Nos. 3332023151
- he Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-RC350-04;the CAMS Innovation Fund for Medical Sciences,Nos. 2021-I2M-1-026, 2022-I2M-2-002-2, and 2021-I2M-3-001;the National Key Research and Development Program of China,No. 2022YFE0111700
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Affiliation(s)
- Siqi Zhang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, China
| | - Xingkai Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, China
| | - Xin Gao
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, China
| | - Xueyao Chen
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, China
| | - Linger Li
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, China
| | - Guoqing Li
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, China
| | - Can Liu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, China
| | - Yuan Miao
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, China
| | - Rui Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, China.
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, Lanzhou University, 2019RU066, 730000, Lanzhou, China.
| | - Kuan Hu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, China.
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Sergieva S, Sofiyanski T, Robev B, Dimcheva M, Fakirova A. Retrospective study of post-treatment 131I SPECT/CT imaging for personalizing therapy of patients with differentiated thyroid cancer. Folia Med (Plovdiv) 2024; 66:776-786. [PMID: 39774349 DOI: 10.3897/folmed.66.e139177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 11/25/2024] [Indexed: 01/11/2025] Open
Abstract
INTRODUCTION The absence of anatomical landmarks in the whole body scan makes it challenging to precisely localize 131I uptake, which is used to treat patients with differentiated thyroid cancer (DTC). Recently, SPECT/CT studies have been utilized to increase the diagnostic sensitivity and specificity.
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Affiliation(s)
| | | | - Bozhil Robev
- St Ivan Rilski University Hospital, Sofia, Bulgaria
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Le TD, Shitiri NC, Jung SH, Kwon SY, Lee C. Image Synthesis in Nuclear Medicine Imaging with Deep Learning: A Review. SENSORS (BASEL, SWITZERLAND) 2024; 24:8068. [PMID: 39771804 PMCID: PMC11679239 DOI: 10.3390/s24248068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 12/13/2024] [Accepted: 12/13/2024] [Indexed: 01/11/2025]
Abstract
Nuclear medicine imaging (NMI) is essential for the diagnosis and sensing of various diseases; however, challenges persist regarding image quality and accessibility during NMI-based treatment. This paper reviews the use of deep learning methods for generating synthetic nuclear medicine images, aimed at improving the interpretability and utility of nuclear medicine protocols. We discuss advanced image generation algorithms designed to recover details from low-dose scans, uncover information hidden by specific radiopharmaceutical properties, and enhance the sensing of physiological processes. By analyzing 30 of the newest publications in this field, we explain how deep learning models produce synthetic nuclear medicine images that closely resemble their real counterparts, significantly enhancing diagnostic accuracy when images are acquired at lower doses than the clinical policies' standard. The implementation of deep learning models facilitates the combination of NMI with various imaging modalities, thereby broadening the clinical applications of nuclear medicine. In summary, our review underscores the significant potential of deep learning in NMI, indicating that synthetic image generation may be essential for addressing the existing limitations of NMI and improving patient outcomes.
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Affiliation(s)
- Thanh Dat Le
- Department of Artificial Intelligence Convergence, Chonnam National University, Gwangju 61186, Jeollanam-do, Republic of Korea; (T.D.L.); (N.C.S.)
| | - Nchumpeni Chonpemo Shitiri
- Department of Artificial Intelligence Convergence, Chonnam National University, Gwangju 61186, Jeollanam-do, Republic of Korea; (T.D.L.); (N.C.S.)
| | - Sung-Hoon Jung
- Department of Hematology-Oncology, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun 58128, Jeollanam-do, Republic of Korea;
| | - Seong-Young Kwon
- Department of Nuclear Medicine, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun 58128, Jeollanam-do, Republic of Korea;
| | - Changho Lee
- Department of Artificial Intelligence Convergence, Chonnam National University, Gwangju 61186, Jeollanam-do, Republic of Korea; (T.D.L.); (N.C.S.)
- Department of Nuclear Medicine, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun 58128, Jeollanam-do, Republic of Korea;
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Kim SM, Lee JS. A comprehensive review on Compton camera image reconstruction: from principles to AI innovations. Biomed Eng Lett 2024; 14:1175-1193. [PMID: 39465108 PMCID: PMC11502649 DOI: 10.1007/s13534-024-00418-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 08/09/2024] [Accepted: 08/20/2024] [Indexed: 10/29/2024] Open
Abstract
Compton cameras have emerged as promising tools in biomedical imaging, offering sensitive gamma-ray imaging capabilities for diverse applications. This review paper comprehensively overviews the latest advancements in Compton camera image reconstruction technologies. Beginning with a discussion of the fundamental principles of Compton scattering and its relevance to gamma-ray imaging, the paper explores the key components and design considerations of Compton camera systems. We then review various image reconstruction algorithms employed in Compton camera systems, including analytical, iterative, and statistical approaches. Recent developments in machine learning-based reconstruction methods are also discussed, highlighting their potential to enhance image quality and reduce reconstruction time in biomedical applications. In particular, we focus on the challenges posed by conical back-projection in Compton camera image reconstruction, and how innovative signal processing techniques have addressed these challenges to improve image accuracy and spatial resolution. Furthermore, experimental validations of Compton camera imaging in preclinical and clinical settings, including multi-tracer and whole-gamma imaging studies are introduced. In summary, this review provides potentially useful information about the current state-of-the-art Compton camera image reconstruction technologies, offering a helpful guide for investigators new to this field.
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Affiliation(s)
- Soo Mee Kim
- Maritime ICT & Mobility Research Department, Korea Institute of Ocean Science and Technology, Busan, Korea
| | - Jae Sung Lee
- Department of Nuclear Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080 Korea
- Brightonix Imaging Inc., Seoul, Korea
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Zhang C, Li T, Zhao Q, Ma R, Hong Z, Huang X, Gao P, Liu J, Zhao J, Wang Z. Advances and Prospects in Liquid Biopsy Techniques for Malignant Tumor Diagnosis and Surveillance. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2404709. [PMID: 39082395 DOI: 10.1002/smll.202404709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 07/07/2024] [Indexed: 11/02/2024]
Abstract
Liquid biopsy technology provides invaluable support for the early diagnosis of tumors and surveillance of disease course by detecting tumor-related biomarkers in bodily fluids. Currently, liquid biopsy techniques are mainly divided into two categories: biomarker and label-free. Biomarker liquid biopsy techniques utilize specific antibodies or probes to identify and isolate target cells, exosomes, or molecules, and these techniques are widely used in clinical practice. However, they have certain limitations including dependence on tumor markers, alterations in cell biological properties, and high cost. In contrast, label-free liquid biopsy techniques directly utilize physical or chemical properties of cells, exosomes, or molecules for detection and isolation. These techniques have the advantage of not needing labeling, not impacting downstream analysis, and low detection cost. However, most are still in the research stage and not yet mature. This review first discusses recent advances in liquid biopsy techniques for early tumor diagnosis and disease surveillance. Several current techniques are described in detail. These techniques exploit differences in biomarkers, size, density, deformability, electrical properties, and chemical composition in tumor components to achieve highly sensitive tumor component identification and separation. Finally, the current research progress is summarized and the future research directions of the field are discussed.
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Affiliation(s)
- Chengzhi Zhang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 N Nanjing Street, Shenyang, Liaoning, 110001, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
- Institute of Health Sciences, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
| | - Tenghui Li
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 N Nanjing Street, Shenyang, Liaoning, 110001, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
- Institute of Health Sciences, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
| | - Qian Zhao
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
- Institute of Health Sciences, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
| | - Rui Ma
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 N Nanjing Street, Shenyang, Liaoning, 110001, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
- Institute of Health Sciences, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
| | - Zhengchao Hong
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 N Nanjing Street, Shenyang, Liaoning, 110001, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
- Institute of Health Sciences, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
| | - Xuanzhang Huang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 N Nanjing Street, Shenyang, Liaoning, 110001, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
- Institute of Health Sciences, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
| | - Peng Gao
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 N Nanjing Street, Shenyang, Liaoning, 110001, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
- Institute of Health Sciences, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
| | - Jingjing Liu
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 N Nanjing Street, Shenyang, Liaoning, 110001, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
- Institute of Health Sciences, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
| | - Junhua Zhao
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 N Nanjing Street, Shenyang, Liaoning, 110001, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
- Institute of Health Sciences, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
| | - Zhenning Wang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 N Nanjing Street, Shenyang, Liaoning, 110001, China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
- Institute of Health Sciences, China Medical University, No.77 Puhe Road, Shenyang, Liaoning, 110122, China
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Andrew J, Ezra-Manicum AL, Witika BA. Developments in radionanotheranostic strategies for precision diagnosis and treatment of prostate cancer. EJNMMI Radiopharm Chem 2024; 9:62. [PMID: 39180599 PMCID: PMC11344754 DOI: 10.1186/s41181-024-00295-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 08/13/2024] [Indexed: 08/26/2024] Open
Abstract
BACKGROUND Prostate Cancer (PCa) is the second most diagnosed urological cancer among men worldwide. Conventional methods used for diagnosis of PCa have several pitfalls which include lack of sensitivity and specificity. On the other hand, traditional treatment of PCa poses challenges such as long-term side effects and the development of multidrug resistance (MDR). MAIN BODY Hence, there is a need for novel PCa agents with the potential to lessen the burden of these adverse effects on patients. Nanotechnology has emerged as a promising approach to support both early diagnosis and effective treatment of tumours by ensuring precise delivery of the drug to the targeted site of the disease. Most cancer-related biological processes occur on the nanoscale hence application of nanotechnology has been greatly appreciated and implemented in the management and therapeutics of cancer. Nuclear medicine plays a significant role in the non-invasive diagnosis and treatment of PCa using appropriate radiopharmaceuticals. This review aims to explore the different radiolabelled nanomaterials to enhance the specific delivery of imaging and therapeutic agents to cancer cells. Thereafter, the review appraises the advantages and disadvantages of these modalities and then discusses and outlines the benefits of radiolabelled nanomaterials in targeting cancerous prostatic tumours. Moreover, the nanoradiotheranostic approaches currently developed for PCa are discussed and finally the prospects of combining radiopharmaceuticals with nanotechnology in improving PCa outcomes will be highlighted. CONCLUSION Nanomaterials have great potential, but safety and biocompatibility issues remain. Notwithstanding, the combination of nanomaterials with radiotherapeutics may improve patient outcomes and quality of life.
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Affiliation(s)
- Jubilee Andrew
- Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria, 0208, South Africa
| | - Amanda-Lee Ezra-Manicum
- Department of Chemistry, Faculty of Science, Tshwane University of Technology (Arcadia Campus), Pretoria, South Africa
| | - Bwalya Angel Witika
- Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria, 0208, South Africa.
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Alqahtani MM. Whole-Body SPECT/CT: Protocol Variation and Technical Consideration-A Narrative Review. Diagnostics (Basel) 2024; 14:1827. [PMID: 39202315 PMCID: PMC11353707 DOI: 10.3390/diagnostics14161827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 08/13/2024] [Accepted: 08/16/2024] [Indexed: 09/03/2024] Open
Abstract
Introducing a hybrid imaging approach, such as single-photon emission computerized tomography with X-ray computed tomography (SPECT)/CT, improves diagnostic accuracy and patient management. The ongoing advancement of SPECT hardware and software has resulted in the clinical application of novel approaches. For example, whole-body SPECT/CT (WB-SPECT/CT) studies cover multiple consecutive bed positions, similar to positron emission tomography-computed tomography (PET/CT). WB-SPECT/CT proves to be a helpful tool for evaluating bone metastases (BM), reducing equivocal findings, and enhancing user confidence, displaying effective performance in contrast to planar bone scintigraphy (PBS). Consequently, it is increasingly utilized and might substitute PBS, which leads to new questions and issues concerning the acquisition protocol, patient imaging time, and workflow process. Therefore, this review highlights various aspects of WB-SPECT/CT acquisition protocols that need to be considered to help understand WB-SPECT/CT workflow processes and optimize imaging protocols.
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Affiliation(s)
- Mansour M. Alqahtani
- Department of Radiology and Medical Imaging, Faculty of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia;
- Discipline of Medical Imaging Science, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia
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Nguyen AT, Kim HK. Recent Progress in Synthesis of 99mTc-labeled Complexes with Nitroimidazoles as SPECT Probes for Targeting Tumor Hypoxia. Nucl Med Mol Imaging 2024; 58:258-278. [PMID: 39036459 PMCID: PMC11255181 DOI: 10.1007/s13139-024-00860-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 03/29/2024] [Accepted: 04/03/2024] [Indexed: 07/23/2024] Open
Abstract
The majority of solid tumors have hypoxia, or low oxygen levels, which is one of the hallmarks of cancer. Hypoxia was found to relate to cancer metastases and resistance to therapies, therefore, detection of hypoxia plays an important role in the process of cancer prognosis and treatment. Single-photon emission computed tomography (SPECT) is a non-invasive imaging technique using gamma-emitting radiopharmaceuticals to visualize biological activities within the body. SPECT is also applied for the detection of tumor hypoxia with the development of hypoxia-targeting radiopharmaceuticals. Radiopharmaceuticals containing nitroimidazole moieties have received increasing attention due to their bio-reducible characteristics which make the radiopharmaceuticals accumulate in the hypoxia regions. This review summarizes the recent development of 99mTc-labeled radiopharmaceuticals bearing nitroimidazoles for SPECT imaging of tumor hypoxia including the synthetic methods and results of animal studies.
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Affiliation(s)
- Anh Thu Nguyen
- Department of Nuclear Medicine, Jeonbuk National University Medical School and Hospital, Jeonju, 54907 Republic of Korea
| | - Hee-Kwon Kim
- Department of Nuclear Medicine, Jeonbuk National University Medical School and Hospital, Jeonju, 54907 Republic of Korea
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12
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Zheng J, Xiao J, Wang Y, Zhang X. CIRF: Coupled Image Reconstruction and Fusion Strategy for Deep Learning Based Multi-Modal Image Fusion. SENSORS (BASEL, SWITZERLAND) 2024; 24:3545. [PMID: 38894335 PMCID: PMC11175309 DOI: 10.3390/s24113545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 05/26/2024] [Accepted: 05/27/2024] [Indexed: 06/21/2024]
Abstract
Multi-modal medical image fusion (MMIF) is crucial for disease diagnosis and treatment because the images reconstructed from signals collected by different sensors can provide complementary information. In recent years, deep learning (DL) based methods have been widely used in MMIF. However, these methods often adopt a serial fusion strategy without feature decomposition, causing error accumulation and confusion of characteristics across different scales. To address these issues, we have proposed the Coupled Image Reconstruction and Fusion (CIRF) strategy. Our method parallels the image fusion and reconstruction branches which are linked by a common encoder. Firstly, CIRF uses the lightweight encoder to extract base and detail features, respectively, through the Vision Transformer (ViT) and the Convolutional Neural Network (CNN) branches, where the two branches interact to supplement information. Then, two types of features are fused separately via different blocks and finally decoded into fusion results. In the loss function, both the supervised loss from the reconstruction branch and the unsupervised loss from the fusion branch are included. As a whole, CIRF increases its expressivity by adding multi-task learning and feature decomposition. Additionally, we have also explored the impact of image masking on the network's feature extraction ability and validated the generalization capability of the model. Through experiments on three datasets, it has been demonstrated both subjectively and objectively, that the images fused by CIRF exhibit appropriate brightness and smooth edge transition with more competitive evaluation metrics than those fused by several other traditional and DL-based methods.
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Affiliation(s)
| | | | | | - Xuming Zhang
- Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
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13
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Abstract
The recent emergence of nanomedicine has revolutionized the therapeutic landscape and necessitated the creation of more sophisticated drug delivery systems. Polymeric nanoparticles sit at the forefront of numerous promising drug delivery designs, due to their unmatched control over physiochemical properties such as size, shape, architecture, charge, and surface functionality. Furthermore, polymeric nanoparticles have the ability to navigate various biological barriers to precisely target specific sites within the body, encapsulate a diverse range of therapeutic cargo and efficiently release this cargo in response to internal and external stimuli. However, despite these remarkable advantages, the presence of polymeric nanoparticles in wider clinical application is minimal. This review will provide a comprehensive understanding of polymeric nanoparticles as drug delivery vehicles. The biological barriers affecting drug delivery will be outlined first, followed by a comprehensive description of the various nanoparticle designs and preparation methods, beginning with the polymers on which they are based. The review will meticulously explore the current performance of polymeric nanoparticles against a myriad of diseases including cancer, viral and bacterial infections, before finally evaluating the advantages and crucial challenges that will determine their wider clinical potential in the decades to come.
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Affiliation(s)
- Maximilian
A. Beach
- School
of Chemistry, The University of Melbourne, Parkville, Victoria 3010, Australia
| | - Umeka Nayanathara
- School
of Chemistry, The University of Melbourne, Parkville, Victoria 3010, Australia
| | - Yanting Gao
- School
of Chemistry, The University of Melbourne, Parkville, Victoria 3010, Australia
| | - Changhe Zhang
- School
of Chemistry, The University of Melbourne, Parkville, Victoria 3010, Australia
| | - Yijun Xiong
- School
of Chemistry, The University of Melbourne, Parkville, Victoria 3010, Australia
| | - Yufu Wang
- School
of Chemistry, The University of Melbourne, Parkville, Victoria 3010, Australia
| | - Georgina K. Such
- School
of Chemistry, The University of Melbourne, Parkville, Victoria 3010, Australia
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14
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Garshad J, Salarvand A, Tavakoli M, Mansourian M. Potential of [99mTc] Tc-IONPs in SPECT: a systematic review on efficiency and accumulation rates. J Radioanal Nucl Chem 2024; 333:2231-2250. [DOI: 10.1007/s10967-024-09480-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 03/28/2024] [Indexed: 10/14/2024]
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Fujita K, Urano Y. Activity-Based Fluorescence Diagnostics for Cancer. Chem Rev 2024; 124:4021-4078. [PMID: 38518254 DOI: 10.1021/acs.chemrev.3c00612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/24/2024]
Abstract
Fluorescence imaging is one of the most promising approaches to achieve intraoperative assessment of the tumor/normal tissue margins during cancer surgery. This is critical to improve the patients' prognosis, and therefore various molecular fluorescence imaging probes have been developed for the identification of cancer lesions during surgery. Among them, "activatable" fluorescence probes that react with cancer-specific biomarker enzymes to generate fluorescence signals have great potential for high-contrast cancer imaging due to their low background fluorescence and high signal amplification by enzymatic turnover. Over the past two decades, activatable fluorescence probes employing various fluorescence control mechanisms have been developed worldwide for this purpose. Furthermore, new biomarker enzymatic activities for specific types of cancers have been identified, enabling visualization of various types of cancers with high sensitivity and specificity. This Review focuses on recent advances in the design, function and characteristics of activatable fluorescence probes that target cancer-specific enzymatic activities for cancer imaging and also discusses future prospects in the field of activity-based diagnostics for cancer.
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16
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Wang Z, Li G, Zhao Q, Fu G, Yang Z, Zhang G. Reductive prodrug and AIE copolymer nanoparticle for monitoring and chemotherapy. BMC Cancer 2024; 24:382. [PMID: 38532345 DOI: 10.1186/s12885-024-12135-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 03/17/2024] [Indexed: 03/28/2024] Open
Abstract
Polymeric micelle systems for drug delivery, monitor and chemotherapy have gained significant attention, and reductive polymeric micelle systems have become particularly attractive due to their controlled release behavior without additional assistance. However, there are challenges in accurately controlling drug and probe release from the nanoparticles and determining the loading content of drug and probe. To address these issues, we have developed a reduction-responsive Pt(IV) prodrug-based polymeric delivery system that can be dynamically monitored using aggregation-induced emission luminogens (AIE) based bioprobes. These polymeric micelle can self-assemble into nanoparticles and release both bio-active Pt(II) drug and bio-probe upon reduction activation. TPE molecules released in the inner endo/lysosomal microenvironment aggregate and fluoresce upon irradiation, thus allowing real-time tracking of drug biodistribution without additional contrast agents. Advantages of this system include position-specific chemical bond cleavage, control of platinum content, and monitoring of drug reduction and biodistribution.
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Affiliation(s)
- Zigui Wang
- Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- NMPA Key Laboratory for Quality Control of In Vitro Diagnostics, Beijing, China
- Beijing Engineering Research Center of Immunological Reagents Clinical Research, Beijing, China
- Zhengzhou Immunobiotech Co, Ltd, Zhengzhou, 450016, P.R. China
| | - Guilin Li
- Zhengzhou Immunobiotech Co, Ltd, Zhengzhou, 450016, P.R. China
| | - Qiaohui Zhao
- Zhengzhou Immunobiotech Co, Ltd, Zhengzhou, 450016, P.R. China
| | - Guangyu Fu
- Autobio Diagnostics Co, LtdHenan, 450016, China
| | - Zengli Yang
- Autobio Diagnostics Co, LtdHenan, 450016, China
| | - Guojun Zhang
- Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
- NMPA Key Laboratory for Quality Control of In Vitro Diagnostics, Beijing, China.
- Beijing Engineering Research Center of Immunological Reagents Clinical Research, Beijing, China.
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Liu P, Shi J. Assessment of unilateral condylar hyperplasia with quantitative SPECT/CT. Heliyon 2024; 10:e23777. [PMID: 38192797 PMCID: PMC10772615 DOI: 10.1016/j.heliyon.2023.e23777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 11/29/2023] [Accepted: 12/13/2023] [Indexed: 01/10/2024] Open
Abstract
Purpose The current study aimedto assess condylar activityin patients with unilateral condylar hyperplasia (UCH) with quantitative SPECT/CT. Patients and methods This retrospective study included patients with UCH who underwent quantitative SPECT/CT. SPECT analysis and quantification of SPECT/CT were performed, and the maximum count per pixel and SUVmax of either side of the condyles were calculated. Results 39 patients were included in the analysisand classified into three subgroups according to the percentile differential right-left ratio: inactive group, left active (LA) group, and right active (RA) group. Totally, the SUVmax of the affected side is significantly higher than the unaffected side (active:5.93 ± 2.43 vs inactive:3.62 ± 1.76, P < 0.001), SUVmax-based ratios correlated well with the ratios based on maximum count (R = 0.944, P < 0.001). ROC analysis showed poorSUVmaxperformance in differentiation between theactive condyles and the inactive condyles due to the lower area under the curve (AUC) (0.588). In subgroup analysis, the affected side is significantly higher than the unaffected side in active groups with SUVmax, no significant difference was found between the active sides or the inactive sides of active groups. Interestingly, the SUVmax of the left side was statistically higher than that of the right sidein the inactive group (P = 0.01),while the left side of the right active group has significantlylower activitythan that in the inactive group, meanwhile,the right side showed no significant difference. Furthermore, each side showed no significant difference between the left active group and the inactive group. Conclusions SUVmax is not an optimal measurement effectively used to evaluate active condyles. However, SUV ratios correlated well with the count ratios, and the left side of condyles showed a peculiar feature in condyle growth status reflected in radioactivity quantified with SPECT/CT, which needs further study to determine the role in the development of the UCH.
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Affiliation(s)
| | - Jun Shi
- Department of Oral and Craniomaxillofacial Science, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Fayez H, Selim A, Shamma R, Rashed H. Intranasal Radioiodinated Ferulic Acid Polymeric Micelles as the First Nuclear Medicine Imaging Probe for ETRA Brain Receptor. Curr Radiopharm 2024; 17:209-217. [PMID: 38213167 DOI: 10.2174/0118744710269885231113070356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 08/17/2023] [Accepted: 09/27/2023] [Indexed: 01/13/2024]
Abstract
INTRODUCTION The aim of this work was to prepare a selective nuclear medicine imaging probe for the Endothelin 1 receptor A in the brain. MATERIAL AND METHODS Ferulic acid (an ETRA antagonist) was radiolabeled using 131I by direct electrophilic substitution method. The radiolabeled ferulic acid was formulated as polymeric micelles to allow intranasal brain delivery. Biodistribution was studied in Swiss albino mice by comparing brain uptake of 131I-ferulic acid after IN administration of 131I-ferulic acid polymeric micelles, IN administration of 131I-ferulic acid solution and IV administration of 131I-ferulic acid solution. RESULTS Successful radiolabeling was achieved with an RCY of 98 % using 200 μg of ferulic acid and 60 μg of CAT as oxidizing agents at pH 6, room temperature and 30 min reaction time. 131I-ferulic acid polymeric micelles were successfully formulated with the particle size of 21.63 nm and polydispersity index of 0.168. Radioactivity uptake in the brain and brain/blood uptake ratio for I.N 131I-ferulic acid polymeric micelles were greater than the two other routes at all periods. CONCLUSION Our results provide 131I-ferulic acid polymeric micelles as a hopeful nuclear medicine tracer for ETRA brain receptor.
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Affiliation(s)
- Hend Fayez
- Department of Labeled Compounds, Hot Laboratories Center, Egyptian Atomic Energy Authority, Cairo, Egypt
| | - Adli Selim
- Department of Labeled Compounds, Hot Laboratories Center, Egyptian Atomic Energy Authority, Cairo, Egypt
| | - Rehab Shamma
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11561, Egypt
| | - Hassan Rashed
- Department of Labeled Compounds, Hot Laboratories Center, Egyptian Atomic Energy Authority, Cairo, Egypt
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Sinai University, Kantara, Egypt
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Dobrucki IT, Miskalis A, Nelappana M, Applegate C, Wozniak M, Czerwinski A, Kalinowski L, Dobrucki LW. Receptor for advanced glycation end-products: Biological significance and imaging applications. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2024; 16:e1935. [PMID: 37926944 DOI: 10.1002/wnan.1935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 09/25/2023] [Accepted: 10/09/2023] [Indexed: 11/07/2023]
Abstract
The receptor for advanced glycation end-products (RAGE or AGER) is a transmembrane, immunoglobulin-like receptor that, due to its multiple isoform structures, binds to a diverse range of endo- and exogenous ligands. RAGE activation caused by the ligand binding initiates a cascade of complex pathways associated with producing free radicals, such as reactive nitric oxide and oxygen species, cell proliferation, and immunoinflammatory processes. The involvement of RAGE in the pathogenesis of disorders such as diabetes, inflammation, tumor progression, and endothelial dysfunction is dictated by the accumulation of advanced glycation end-products (AGEs) at pathologic states leading to sustained RAGE upregulation. The involvement of RAGE and its ligands in numerous pathologies and diseases makes RAGE an interesting target for therapy focused on the modulation of both RAGE expression or activation and the production or exogenous administration of AGEs. Despite the known role that the RAGE/AGE axis plays in multiple disease states, there remains an urgent need to develop noninvasive, molecular imaging approaches that can accurately quantify RAGE levels in vivo that will aid in the validation of RAGE and its ligands as biomarkers and therapeutic targets. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Diagnostic Tools > Biosensing.
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Affiliation(s)
- Iwona T Dobrucki
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
- Beckman Institute for Advanced Science and Technology, Urbana, Illinois, USA
- Department of Biomedical and Translational Sciences, Carle-Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
- Academy of Medical and Social Applied Sciences, Elblag, Poland
| | - Angelo Miskalis
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
| | - Michael Nelappana
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
- Beckman Institute for Advanced Science and Technology, Urbana, Illinois, USA
| | - Catherine Applegate
- Beckman Institute for Advanced Science and Technology, Urbana, Illinois, USA
- Cancer Center at Illinois, Urbana, Illinois, USA
| | - Marcin Wozniak
- Beckman Institute for Advanced Science and Technology, Urbana, Illinois, USA
- Division of Medical Laboratory Diagnostics-Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdansk, Poland
| | - Andrzej Czerwinski
- Beckman Institute for Advanced Science and Technology, Urbana, Illinois, USA
| | - Leszek Kalinowski
- Beckman Institute for Advanced Science and Technology, Urbana, Illinois, USA
- Division of Medical Laboratory Diagnostics-Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdansk, Poland
- BioTechMed Centre, Department of Mechanics of Materials and Structures, Gdansk University of Technology, Gdansk, Poland
| | - Lawrence W Dobrucki
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
- Beckman Institute for Advanced Science and Technology, Urbana, Illinois, USA
- Department of Biomedical and Translational Sciences, Carle-Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
- Cancer Center at Illinois, Urbana, Illinois, USA
- Division of Medical Laboratory Diagnostics-Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdansk, Poland
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Lin B, Xiao F, Jiang J, Zhao Z, Zhou X. Engineered aptamers for molecular imaging. Chem Sci 2023; 14:14039-14061. [PMID: 38098720 PMCID: PMC10718180 DOI: 10.1039/d3sc03989g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 11/07/2023] [Indexed: 12/17/2023] Open
Abstract
Molecular imaging, including quantification and molecular interaction studies, plays a crucial role in visualizing and analysing molecular events occurring within cells or organisms, thus facilitating the understanding of biological processes. Moreover, molecular imaging offers promising applications for early disease diagnosis and therapeutic evaluation. Aptamers are oligonucleotides that can recognize targets with a high affinity and specificity by folding themselves into various three-dimensional structures, thus serving as ideal molecular recognition elements in molecular imaging. This review summarizes the commonly employed aptamers in molecular imaging and outlines the prevalent design approaches for their applications. Furthermore, it highlights the successful application of aptamers to a wide range of targets and imaging modalities. Finally, the review concludes with a forward-looking perspective on future advancements in aptamer-based molecular imaging.
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Affiliation(s)
- Bingqian Lin
- College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers-Ministry of Education, Department of Hematology of Zhongnan Hospital, Taikang Center for Life and Medical Sciences, Wuhan University Wuhan 430072 China
| | - Feng Xiao
- College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers-Ministry of Education, Department of Hematology of Zhongnan Hospital, Taikang Center for Life and Medical Sciences, Wuhan University Wuhan 430072 China
| | - Jinting Jiang
- College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers-Ministry of Education, Department of Hematology of Zhongnan Hospital, Taikang Center for Life and Medical Sciences, Wuhan University Wuhan 430072 China
| | - Zhengjia Zhao
- College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers-Ministry of Education, Department of Hematology of Zhongnan Hospital, Taikang Center for Life and Medical Sciences, Wuhan University Wuhan 430072 China
| | - Xiang Zhou
- College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers-Ministry of Education, Department of Hematology of Zhongnan Hospital, Taikang Center for Life and Medical Sciences, Wuhan University Wuhan 430072 China
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Tomita Y, Ichikawa Y, Hashizume K, Sakuma H. Effect of Gaussian Smoothing Filter Size for CT-Based Attenuation Correction on Quantitative Assessment of Bone SPECT/CT: A Phantom Study. J Digit Imaging 2023; 36:2313-2321. [PMID: 37322307 PMCID: PMC10501997 DOI: 10.1007/s10278-023-00864-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 05/15/2023] [Accepted: 05/30/2023] [Indexed: 06/17/2023] Open
Abstract
This study aims to determine the effect of Gaussian filter size for CT-based attenuation correction (CTAC) on the quantitative assessment of bone SPECT. An experiment was performed using a cylindrical phantom containing six rods, of which one was filled with water and five were filled with various concentrations of K2HPO4 solution (120-960 mg/cm3) to simulate different bone densities. 99mTc-solution of 207 kBq/ml was also included within the rods. SPECT data were acquired at 120 views for 30 s/view. CT for attenuation correction were obtained at 120 kVp and 100 mA. Sixteen different CTAC maps processed with different Gaussian filter sizes (ranging from 0 to 30 mm in 2 mm increments) were generated. SPECT images were reconstructed for each of the 16 CTAC maps. Attenuation coefficients and radioactivity concentrations in the rods were compared with those in the water-filled rod without K2HPO4 solution as a reference. Gaussian filter sizes below 14-16 mm resulted in an overestimation of radioactivity concentrations for rods with high concentrations of K2HPO4 (≥ 666 mg/cm3). The overestimation of radioactivity concentration measurement was 3.8% and 5.5% for 666 mg/cm3 and 960 mg/cm3 K2HPO4 solutions, respectively. The difference in radioactivity concentration between the water rod and the K2HPO4 rods was minimal at 18-22 mm. The use of Gaussian filter sizes smaller than 14-16 mm caused an overestimation of radioactivity concentration in regions of high CT values. Setting the Gaussian filter size to 18-22 mm enables radioactivity concentration to be measured with the least influence on bone density.
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Affiliation(s)
- Yoya Tomita
- Central Division of Radiology, Mie University Hospital, 2-174 Edobashi, Tsu, Mie 514-8507 Japan
| | - Yasutaka Ichikawa
- Department of Radiology, Mie University Hospital, 2-174 Edobashi, Tsu, Mie 514-8507 Japan
| | - Kengo Hashizume
- Central Division of Radiology, Mie University Hospital, 2-174 Edobashi, Tsu, Mie 514-8507 Japan
| | - Hajime Sakuma
- Department of Radiology, Mie University Hospital, 2-174 Edobashi, Tsu, Mie 514-8507 Japan
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Peters JP, Brahms A, Janicaud V, Anikeeva M, Peschke E, Ellermann F, Ferrari A, Hellmold D, Held-Feindt J, Kim NM, Meiser J, Aden K, Herges R, Hövener JB, Pravdivtsev AN. Nitrogen-15 dynamic nuclear polarization of nicotinamide derivatives in biocompatible solutions. SCIENCE ADVANCES 2023; 9:eadd3643. [PMID: 37611105 PMCID: PMC10446501 DOI: 10.1126/sciadv.add3643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 07/21/2023] [Indexed: 08/25/2023]
Abstract
Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance imaging by more than 10,000 times, enabling in vivo metabolic imaging to be performed noninvasively in real time. Here, we are developing a group of dDNP polarized tracers based on nicotinamide (NAM). We synthesized 1-15N-NAM and 1-15N nicotinic acid and hyperpolarized them with dDNP, reaching (13.0 ± 1.9)% 15N polarization. We found that the lifetime of hyperpolarized 1-15N-NAM is strongly field- and pH-dependent, with T1 being as long as 41 s at a pH of 12 and 1 T while as short as a few seconds at neutral pH and fields below 1 T. The remarkably short 1-15N lifetime at low magnetic fields and neutral pH drove us to establish a unique pH neutralization procedure. Using 15N dDNP and an inexpensive rodent imaging probe designed in-house, we acquired a 15N MRI of 1-15N-NAM (previously hyperpolarized for more than an hour) in less than 1 s.
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Affiliation(s)
- Josh P. Peters
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center Kiel, Kiel University, Am Botanischen Garten 14, 24118 Kiel, Germany
| | - Arne Brahms
- Otto Diels Institute for Organic Chemistry, Kiel University, Otto-Hahn Platz 4, 24098 Kiel, Germany
| | - Vivian Janicaud
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center Kiel, Kiel University, Am Botanischen Garten 14, 24118 Kiel, Germany
| | - Maria Anikeeva
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center Kiel, Kiel University, Am Botanischen Garten 14, 24118 Kiel, Germany
| | - Eva Peschke
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center Kiel, Kiel University, Am Botanischen Garten 14, 24118 Kiel, Germany
| | - Frowin Ellermann
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center Kiel, Kiel University, Am Botanischen Garten 14, 24118 Kiel, Germany
| | - Arianna Ferrari
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center Kiel, Kiel University, Am Botanischen Garten 14, 24118 Kiel, Germany
| | - Dana Hellmold
- Department of Neurosurgery, University Medical Center Kiel, Arnold-Heller-Str. 3, House D, 24105 Kiel, Germany
| | - Janka Held-Feindt
- Department of Neurosurgery, University Medical Center Kiel, Arnold-Heller-Str. 3, House D, 24105 Kiel, Germany
| | - Na-mi Kim
- Institute of Clinical Molecular Biology, Kiel University, Rosalind-Franklin-Straße 12, 24105 Kiel, Germany
| | - Johannes Meiser
- Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, 6A Rue Nicolas-Ernest Barblé, 1210 Luxembourg, Luxembourg
| | - Konrad Aden
- Institute of Clinical Molecular Biology, Kiel University, Rosalind-Franklin-Straße 12, 24105 Kiel, Germany
- Department of Internal Medicine I, University Medical Center Kiel, Kiel, Germany
| | - Rainer Herges
- Otto Diels Institute for Organic Chemistry, Kiel University, Otto-Hahn Platz 4, 24098 Kiel, Germany
| | - Jan-Bernd Hövener
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center Kiel, Kiel University, Am Botanischen Garten 14, 24118 Kiel, Germany
| | - Andrey N. Pravdivtsev
- Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center Kiel, Kiel University, Am Botanischen Garten 14, 24118 Kiel, Germany
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Veron Sanchez A, Santamaria Guinea N, Cayon Somacarrera S, Bennouna I, Pezzullo M, Bali MA. Rare Solid Pancreatic Lesions on Cross-Sectional Imaging. Diagnostics (Basel) 2023; 13:2719. [PMID: 37627978 PMCID: PMC10453474 DOI: 10.3390/diagnostics13162719] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/15/2023] [Accepted: 08/18/2023] [Indexed: 08/27/2023] Open
Abstract
Several solid lesions can be found within the pancreas mainly arising from the exocrine and endocrine pancreatic tissue. Among all pancreatic malignancies, the most common subtype is pancreatic ductal adenocarcinoma (PDAC), to a point that pancreatic cancer and PDAC are used interchangeably. But, in addition to PDAC, and to the other most common and well-known solid lesions, either related to benign conditions, such as pancreatitis, or not so benign, such as pancreatic neuroendocrine neoplasms (pNENs), there are solid pancreatic lesions considered rare due to their low incidence. These lesions may originate from a cell line with a differentiation other than exocrine/endocrine, such as from the nerve sheath as for pancreatic schwannoma or from mesenchymal cells as for solitary fibrous tumour. These rare solid pancreatic lesions may show a behaviour that ranges in a benign to highly aggressive malignant spectrum. This review includes cases of an intrapancreatic accessory spleen, pancreatic tuberculosis, solid serous cystadenoma, solid pseudopapillary tumour, pancreatic schwannoma, purely intraductal neuroendocrine tumour, pancreatic fibrous solitary tumour, acinar cell carcinoma, undifferentiated carcinoma with osteoclastic-like giant cells, adenosquamous carcinoma, colloid carcinoma of the pancreas, primary leiomyosarcoma of the pancreas, primary and secondary pancreatic lymphoma and metastases within the pancreas. Therefore, it is important to determine the correct diagnosis to ensure optimal patient management. Because of their rarity, their existence is less well known and, when depicted, in most cases incidentally, the correct diagnosis remains challenging. However, there are some typical imaging features present on cross-sectional imaging modalities that, taken into account with the clinical and biological context, contribute substantially to achieve the correct diagnosis.
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Affiliation(s)
- Ana Veron Sanchez
- Hôpital Universitaire de Bruxelles, Institut Jules Bordet, 1070 Brussels, Belgium; (I.B.)
| | | | | | - Ilias Bennouna
- Hôpital Universitaire de Bruxelles, Institut Jules Bordet, 1070 Brussels, Belgium; (I.B.)
| | - Martina Pezzullo
- Hôpital Universitaire de Bruxelles, Hôpital Erasme, 1070 Brussels, Belgium
| | - Maria Antonietta Bali
- Hôpital Universitaire de Bruxelles, Institut Jules Bordet, 1070 Brussels, Belgium; (I.B.)
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Hoog C, Verrecchia-Ramos E, Dejust S, Lalire P, Sezin G, Moubtakir A, El Farsaoui K, Caquot PA, Guendouzen S, Morland D, Papathanassiou D. Implementation of xSPECT, xSPECT bone and Broadquant from literature, clinical survey and innovative phantom study with task-based image quality assessment. Phys Med 2023; 112:102611. [PMID: 37329742 DOI: 10.1016/j.ejmp.2023.102611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 04/19/2023] [Accepted: 05/30/2023] [Indexed: 06/19/2023] Open
Abstract
OBJECTIVE From patient and phantom studies, we aimed to highlight an original implementation process and share a two-years experience clinical feedback on xSPECT (xS), xSPECT Bone (xB) and Broadquant quantification (Siemens) for 99mTc-bone and 177Lu-NET (neuroendocrine tumors) imaging. METHODS Firstly, we checked the relevance of implemented protocols and Broadquant module on the basis of literature and with a homogeneous phantom study respectively. Then, we described xS and xB behaviours with reconstruction parameters (10i-0mm to 40i-20mm) and optimized the protocols through a blinded survey (7 physicians). Finally, the preferred 99mTc-bone reconstruction was assessed through an IEC NEMA phantom including liquid bone spheres. Conventional SNR, CNR, spatial resolution, Q.%error, and recovery curves; and innovative NPS, TTF and detectability score d' were performed (ImQuest software). We also sought to review the adoption of these tools in clinical routine and showed the potential of quantitative xB in the context of theranostics (Xofigo®). RESULTS We showed the need of optimization of implemented reconstruction algorithms and pointed out a decay correction particularity with Broadquant. Preferred parameters were 1s-25i-8mm and 1s-25i-5mm for xS/xB-bone and xS-NET imaging respectively. The phantom study highlighted the different image quality especially for the enhanced spatial resolution xB algorithm (1/TTF10%=2.1 mm) and showed F3D and xB shared the best performances in terms of image quality and quantification. xS was generally less efficient. CONCLUSIONS Qualitative F3D still remains the clinical standard, xB and Broadquant offer challenging perspectives in theranostics. We introduced the potential of innovative metrics for image quality analysis and showed how CT tools should be adapted to fit nuclear medicine imaging.
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Affiliation(s)
| | | | | | - Paul Lalire
- Nuclear Medicine Department, Institut Godinot, Reims, France
| | - Ghali Sezin
- Nuclear Medicine Department, Institut Godinot, Reims, France
| | | | | | | | | | - David Morland
- Nuclear Medicine Department, Institut Godinot, Reims, France; UFR de médecine, université de Reims-Champagne Ardenne, 1, rue Cognacq-Jay, 51095 Reims cedex, France; CReSTIC Centre de recherche en sciences et technologies de l'information et de la communication, EA 3804, université de Reims-Champagne Ardenne, Moulin de la Housse, BP 1039, 51687 Reims Cedex 2, France
| | - Dimitri Papathanassiou
- Nuclear Medicine Department, Institut Godinot, Reims, France; UFR de médecine, université de Reims-Champagne Ardenne, 1, rue Cognacq-Jay, 51095 Reims cedex, France; CReSTIC Centre de recherche en sciences et technologies de l'information et de la communication, EA 3804, université de Reims-Champagne Ardenne, Moulin de la Housse, BP 1039, 51687 Reims Cedex 2, France
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Feng L, Li S, Wang C, Yang J. Current Status and Future Perspective on Molecular Imaging and Treatment of Neuroblastoma. Semin Nucl Med 2023; 53:517-529. [PMID: 36682980 DOI: 10.1053/j.semnuclmed.2022.12.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/02/2022] [Accepted: 12/15/2022] [Indexed: 01/22/2023]
Abstract
Neuroblastoma is the most common extracranial solid tumor in children and arises from anywhere along the sympathetic nervous system. It is a highly heterogeneous disease with a wide range of prognosis, from spontaneous regression or maturing to highly aggressive. About half of pediatric neuroblastoma patients develop the metastatic disease at diagnosis, which carries a poor prognosis. Nuclear medicine plays a pivotal role in the diagnosis, staging, response assessment, and long-term follow-up of neuroblastoma. And it has also played a prominent role in the treatment of neuroblastoma. Because the structure of metaiodobenzylguanidine (MIBG) is similar to that of norepinephrine, 90% of neuroblastomas are MIBG-avid. 123I-MIBG whole-body scintigraphy is the standard nuclear imaging technique for neuroblastoma, usually in combination with SPECT/CT. However, approximately 10% of neuroblastomas are MIBG nonavid. PET imaging has many technical advantages over SPECT imaging, such as higher spatial and temporal resolution, higher sensitivity, superior quantitative capability, and whole-body tomographic imaging. In recent years, various tracers have been used for imaging neuroblastoma with PET. The importance of patient-specific targeted radionuclide therapy for neuroblastoma therapy has also increased. 131I-MIBG therapy is part of the front-line treatment for children with high-risk neuroblastoma. And peptide receptor radionuclide therapy with radionuclide-labeled somatostatin analogues has been successfully used in the therapy of neuroblastoma. Moreover, radioimmunoimaging has important applications in the diagnosis of neuroblastoma, and radioimmunotherapy may provide a novel treatment modality against neuroblastoma. This review discusses the use of current and novel radiopharmaceuticals in nuclear medicine imaging and therapy of neuroblastoma.
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Affiliation(s)
- Lijuan Feng
- Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Siqi Li
- Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Chaoran Wang
- Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jigang Yang
- Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
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Abstract
Over the last half century, the autofluorescence of the metabolic cofactors NADH (reduced nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide) has been quantified in a variety of cell types and disease states. With the spread of nonlinear optical microscopy techniques in biomedical research, NADH and FAD imaging has offered an attractive solution to noninvasively monitor cell and tissue status and elucidate dynamic changes in cell or tissue metabolism. Various tools and methods to measure the temporal, spectral, and spatial properties of NADH and FAD autofluorescence have been developed. Specifically, an optical redox ratio of cofactor fluorescence intensities and NADH fluorescence lifetime parameters have been used in numerous applications, but significant work remains to mature this technology for understanding dynamic changes in metabolism. This article describes the current understanding of our optical sensitivity to different metabolic pathways and highlights current challenges in the field. Recent progress in addressing these challenges and acquiring more quantitative information in faster and more metabolically relevant formats is also discussed.
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Affiliation(s)
- Irene Georgakoudi
- Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, USA;
- Genetics, Molecular and Cellular Biology Program, Graduate School of Biomedical Sciences, Tufts University, Boston, Massachusetts, USA
| | - Kyle P Quinn
- Department of Biomedical Engineering and the Arkansas Integrative Metabolic Research Center, University of Arkansas, Fayetteville, Arkansas, USA
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De K, Prasad P, Sinha S, Mukhopadhyay S, Roy SS. Synthesis, Characterization, and Biological Evaluation of Radiolabeled Glutamine Conjugated Polymeric Nanoparticles: A Simple Approach for Tumor Imaging. ACS APPLIED BIO MATERIALS 2023. [PMID: 37248067 DOI: 10.1021/acsabm.3c00048] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
Application of nanoradiopharmaceuticals for molecular imaging has gained worldwide importance for their multifaceted potentials focusing on providing a safe and cost-effective approach. Biodistribution studies on such species are capable of bringing nanomedicine to patients. Current therapeutically available labeling strategies suffer from different limitations, including off-target cytotoxicity and radiolabel release over time. Poly(lactic-co-glycolic acid)(PLGA) nanoparticles are biodegradable carriers for a variety of contrast agents that can be employed in medicine with high loading capacity for multimodal imaging agents. Here, glutamine-conjugated PLGA polymers were used to construct polymeric nanoparticles (G-PNP) similar to unconjugated PLGA nanoparticles (PNP)s formulated for ex vivo cell labeling and in vivo tumor scintigraphy studies. G-PNP/PNP, characterized by Fourier-transform infrared, atomic-force-microscopy, particle-size, and zeta-potential studies, were biocompatible as evaluated by MTT assay. G-PNPs were radiolabeled with 99mtechnetium (99mTc) by borohydrite reduction. G-PNPs demonstrated higher cellular uptake than PNPs, with no major cytotoxicity. Radiochemical purity indicated that 99mTc labeled G-PNP (99mTc-G-PNP) can form a stable complex with substantial stability in serum with respect to time. Imaging studies showed that 99mTc-G-PNP significantly accumulated at the C6 glioma cell induced tumor-site in rats. Thus, 99mTc-G-PNP demonstrated favorable characteristics and imaging potential which may make it a promising tumor imaging nanoprobe as a nanoradiopharmaceutical.
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Affiliation(s)
- Kakali De
- Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India
| | - Parash Prasad
- Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India
| | - Samarendu Sinha
- Netaji Subhas Chandra Bose Cancer Hospital, Kolkata 700 094, West Bengal, India
| | - Soma Mukhopadhyay
- Netaji Subhas Chandra Bose Cancer Hospital, Kolkata 700 094, West Bengal, India
| | - Sib Sankar Roy
- Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India
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Yoon EC, Kim JS, Lim CH, Park SB, Park S, Lee KA, Kim HS. Visual Scoring of Sacroiliac Joint/Sacrum Ratios of Single-Photon Emission Computed Tomography/Computed Tomography Images Affords High Sensitivity and Negative Predictive Value in Axial Spondyloarthritis. Diagnostics (Basel) 2023; 13:diagnostics13101725. [PMID: 37238208 DOI: 10.3390/diagnostics13101725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 04/27/2023] [Accepted: 05/12/2023] [Indexed: 05/28/2023] Open
Abstract
Spondyloarthritis (SpA) is characterized by inflammatory back pain. Magnetic resonance imaging (MRI) was the earlier gold standard technique for detecting early inflammatory change. We reassessed the diagnostic utility of sacroiliac joint/sacrum (SIS) ratios of single-photon emission computed tomography/computed tomography (SPECT/CT) for identifying sacroiliitis. We aimed to investigate of SPECT/CT in diagnosing SpA using a rheumatologist's visual scoring of SIS ratios assessment. We conducted a single-center, medical records review study of patients with lower back pain who underwent bone SPECT/CT from August 2016 to April 2020. We employed semiquantitative visual bone scoring methods of SIS ratio. The uptake of each sacroiliac joint was compared to that of the sacrum (0-2). A score of 2 for the sacroiliac joint of either side was considered diagnostic of sacroiliitis. Of the 443 patients assessed, 40 had axial SpA (axSpA), 24 being radiographic axSpA and 16 being nonradiographic axSpA. The sensitivity, specificity, and positive and negative predictive values of SIS ratio of SPECT/CT for axSpA were 87.5%, 56.5%, 16.6%, and 97.8%, respectively. In receiver operating curve analysis, MRI better diagnosed axSpA than did SIS ratio of SPECT/CT. Although the diagnostic utility of SIS ratio of SPECT/CT was inferior to MRI, visual scoring of SPECT/CT affords high sensitivity and negative predictive value in axSpA. When MRI is inappropriate for certain patients, SIS ratio of SPECT/CT is an alternative tool for identifying axSpA in real practice.
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Affiliation(s)
- Eun-Chong Yoon
- Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul 04401, Republic of Korea
| | - Jong-Sun Kim
- Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul 04401, Republic of Korea
| | - Chae Hong Lim
- Department of Nuclear Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul 04401, Republic of Korea
| | - Soo Bin Park
- Department of Nuclear Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul 04401, Republic of Korea
| | - Suyeon Park
- Department of Biostatistics, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul 04401, Republic of Korea
- Department of Applied Statistics, Chung-Ang University, Seoul 156-756, Republic of Korea
| | - Kyung-Ann Lee
- Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul 04401, Republic of Korea
| | - Hyun-Sook Kim
- Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul 04401, Republic of Korea
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Kaur A, Verma N, Singh B, Kumar A, Kumari S, De A, Sharma RR, Singh V. Quantitative liver SPECT/CT is a novel tool to assess liver function, prognosis, and response to treatment in cirrhosis. Front Med (Lausanne) 2023; 10:1118531. [PMID: 37035316 PMCID: PMC10073445 DOI: 10.3389/fmed.2023.1118531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 03/03/2023] [Indexed: 04/11/2023] Open
Abstract
Background Functional liver reserve is an important determinant of survival in cirrhosis. The traditional indocyanine green test (ICG) is cumbersome. Hence, we developed and validated a novel liver imaging, a hybrid of SPECT and CT (Q-SPECT/CT), for evaluating disease severity, outcomes, and response to treatment in decompensated cirrhosis (DC). Methods We recruited a cohort of DC patients at a tertiary institute between 2016-2019. First, we standardized the Q-SPECT/CT across a predefined range of volumes through phantom experiments. Then we performed clinical and laboratory evaluations, ICG test (retention at 15 min), and Q-SPECT/CT at baseline and 12 months of granulocyte colony-stimulating factor (G-CSF) and standard medical treatment (SMT). Results In 109 DC patients, 87.1% males, aged 51 ± 10 years, MELD: 14 (7-21), the percent quantitative liver uptake (%QLU) on Q-SPECT/CT exhibited a strong correlation with CTP (r = -0.728, p < 0.001), MELD (r = -0.743; p < 0.001) and ICG-R-15 (r = -0.720, p < 0.001) at baseline. %QLU had the maximum discrimination (AUC: 0.890-0.920), sensitivity (88.9-90.3%), specificity (81.2-90.7%), and accuracy (85.8-89.4%) than liver volumes on Q-SPECT/CT or ICG test for classifying patients in CTP/MELD based prognostic categories. A significant increase in %QLU (26.09 ± 10.06 to 31.2 ± 12.19, p = 0.001) and improvement in CTP/MELD correlated with better survival of G-CSF treated DC patients (p < 0.05). SMT did not show any improvement in Q-SPECT/CT or clinical severity scores (p > 0.05). %QLU > 25 (adj.H.R.: 0.234, p = 0.003) and G-CSF treatment (adj.H.R.: 0.414, p = 0.009) were independent predictors of better 12-months survival in DC. Conclusion Q-SPECT/CT (%QLU) is a novel non-invasive, diagnostic, prognostic, and theragnostic marker of liver reserve and its functions in cirrhosis patients. Clinical trial registration Clinicaltrials.gov, NCT02451033 and NCT03415698.
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Affiliation(s)
- Amritjyot Kaur
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Nipun Verma
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
- *Correspondence: Nipun Verma,
| | - Baljinder Singh
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
- Baljinder Singh,
| | - Ajay Kumar
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sunita Kumari
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Arka De
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ratti Ram Sharma
- Department of Transfusion Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Virendra Singh
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Jarockyte G, Stasys M, Poderys V, Buivydaite K, Pleckaitis M, Bulotiene D, Matulionyte M, Karabanovas V, Rotomskis R. Biodistribution of Multimodal Gold Nanoclusters Designed for Photoluminescence-SPECT/CT Imaging and Diagnostic. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:nano12193259. [PMID: 36234387 PMCID: PMC9565908 DOI: 10.3390/nano12193259] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 09/15/2022] [Accepted: 09/16/2022] [Indexed: 05/30/2023]
Abstract
Highly biocompatible nanostructures for multimodality imaging are critical for clinical diagnostics improvements in the future. Combining optical imaging with other techniques may lead to important advances in diagnostics. The purpose of such a system would be to combine the individual advantages of each imaging method to provide reliable and accurate information at the site of the disease bypassing the limitations of each. The aim of the presented study was to evaluate biodistribution of the biocompatible technetium-99m labelled bovine serum albumin-gold nanoclusters (99mTc-BSA-Au NCs) as photoluminescence-SPECT/CT agent in experimental animals. It was verified spectroscopically that radiolabelling with 99mTc does not influence the optical properties of BSA-Au NCs within the synthesized 99mTc-BSA-Au NCs bioconjugates. Biodistribution imaging of the 99mTc-BSA-Au NCs in Wistar rats was performed using a clinical SPECT/CT system. In vivo imaging of Wistar rats demonstrated intense cardiac blood pool activity, as well as rapid blood clearance and accumulation in the kidneys, liver, and urinary bladder. Confocal images of kidney, liver and spleen tissues revealed no visible uptake indicating that the circulation lifetime of 99mTc-BSA-Au NCs in the bloodstream might be too short for accumulation in these tissues. The cellular uptake of 99mTc-BSA-Au NCs in kidney cells was also delayed and substantial accumulation was observed only after 24-h incubation. Based on our experiments, it was concluded that 99mTc-BSA-Au NCs could be used as a contrast agent and shows promise as potential diagnostic agents for bloodstream imaging of the excretory organs in vivo.
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Affiliation(s)
- Greta Jarockyte
- Biomedical Physics Laboratory, National Cancer Institute, LT-08406 Vilnius, Lithuania
- Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania
| | - Marius Stasys
- Biomedical Physics Laboratory, National Cancer Institute, LT-08406 Vilnius, Lithuania
| | - Vilius Poderys
- Biomedical Physics Laboratory, National Cancer Institute, LT-08406 Vilnius, Lithuania
| | - Kornelija Buivydaite
- Biomedical Physics Laboratory, National Cancer Institute, LT-08406 Vilnius, Lithuania
- Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania
| | - Marijus Pleckaitis
- Biomedical Physics Laboratory, National Cancer Institute, LT-08406 Vilnius, Lithuania
- Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania
| | - Danute Bulotiene
- Biomedical Physics Laboratory, National Cancer Institute, LT-08406 Vilnius, Lithuania
| | - Marija Matulionyte
- Biomedical Physics Laboratory, National Cancer Institute, LT-08406 Vilnius, Lithuania
| | - Vitalijus Karabanovas
- Biomedical Physics Laboratory, National Cancer Institute, LT-08406 Vilnius, Lithuania
- Department of Chemistry and Bioengineering, Vilnius Gediminas Technical University, LT-10223 Vilnius, Lithuania
| | - Ricardas Rotomskis
- Biomedical Physics Laboratory, National Cancer Institute, LT-08406 Vilnius, Lithuania
- Laser Research Center, Faculty of Physics, Vilnius University, LT-10223 Vilnius, Lithuania
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Xie E, Sung E, Saad E, Trayanova N, Wu KC, Chrispin J. Advanced imaging for risk stratification for ventricular arrhythmias and sudden cardiac death. Front Cardiovasc Med 2022; 9:884767. [PMID: 36072882 PMCID: PMC9441865 DOI: 10.3389/fcvm.2022.884767] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 08/02/2022] [Indexed: 11/13/2022] Open
Abstract
Sudden cardiac death (SCD) is a leading cause of mortality, comprising approximately half of all deaths from cardiovascular disease. In the US, the majority of SCD (85%) occurs in patients with ischemic cardiomyopathy (ICM) and a subset in patients with non-ischemic cardiomyopathy (NICM), who tend to be younger and whose risk of mortality is less clearly delineated than in ischemic cardiomyopathies. The conventional means of SCD risk stratification has been the determination of the ejection fraction (EF), typically via echocardiography, which is currently a means of determining candidacy for primary prevention in the form of implantable cardiac defibrillators (ICDs). Advanced cardiac imaging methods such as cardiac magnetic resonance imaging (CMR), single-photon emission computerized tomography (SPECT) and positron emission tomography (PET), and computed tomography (CT) have emerged as promising and non-invasive means of risk stratification for sudden death through their characterization of the underlying myocardial substrate that predisposes to SCD. Late gadolinium enhancement (LGE) on CMR detects myocardial scar, which can inform ICD decision-making. Overall scar burden, region-specific scar burden, and scar heterogeneity have all been studied in risk stratification. PET and SPECT are nuclear methods that determine myocardial viability and innervation, as well as inflammation. CT can be used for assessment of myocardial fat and its association with reentrant circuits. Emerging methodologies include the development of "virtual hearts" using complex electrophysiologic modeling derived from CMR to attempt to predict arrhythmic susceptibility. Recent developments have paired novel machine learning (ML) algorithms with established imaging techniques to improve predictive performance. The use of advanced imaging to augment risk stratification for sudden death is increasingly well-established and may soon have an expanded role in clinical decision-making. ML could help shift this paradigm further by advancing variable discovery and data analysis.
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Affiliation(s)
- Eric Xie
- Division of Cardiology, Department of Medicine, Section of Cardiac Electrophysiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Eric Sung
- Division of Cardiology, Department of Medicine, Section of Cardiac Electrophysiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States
| | - Elie Saad
- Division of Cardiology, Department of Medicine, Section of Cardiac Electrophysiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Natalia Trayanova
- Division of Cardiology, Department of Medicine, Section of Cardiac Electrophysiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States
| | - Katherine C. Wu
- Division of Cardiology, Department of Medicine, Section of Cardiac Electrophysiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Jonathan Chrispin
- Division of Cardiology, Department of Medicine, Section of Cardiac Electrophysiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
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Production Review of Accelerator-Based Medical Isotopes. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27165294. [PMID: 36014532 PMCID: PMC9415084 DOI: 10.3390/molecules27165294] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 08/15/2022] [Accepted: 08/16/2022] [Indexed: 11/17/2022]
Abstract
The production of reactor-based medical isotopes is fragile, which has meant supply shortages from time to time. This paper reviews alternative production methods in the form of cyclotrons, linear accelerators and neutron generators. Finally, the status of the production of medical isotopes in China is described.
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Deep learning models and traditional automated techniques for brain tumor segmentation in MRI: a review. Artif Intell Rev 2022. [DOI: 10.1007/s10462-022-10245-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
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Crișan G, Moldovean-Cioroianu NS, Timaru DG, Andrieș G, Căinap C, Chiș V. Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade. Int J Mol Sci 2022; 23:5023. [PMID: 35563414 PMCID: PMC9103893 DOI: 10.3390/ijms23095023] [Citation(s) in RCA: 118] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 04/23/2022] [Accepted: 04/28/2022] [Indexed: 02/04/2023] Open
Abstract
Positron emission tomography (PET) uses radioactive tracers and enables the functional imaging of several metabolic processes, blood flow measurements, regional chemical composition, and/or chemical absorption. Depending on the targeted processes within the living organism, different tracers are used for various medical conditions, such as cancer, particular brain pathologies, cardiac events, and bone lesions, where the most commonly used tracers are radiolabeled with 18F (e.g., [18F]-FDG and NA [18F]). Oxygen-15 isotope is mostly involved in blood flow measurements, whereas a wide array of 11C-based compounds have also been developed for neuronal disorders according to the affected neuroreceptors, prostate cancer, and lung carcinomas. In contrast, the single-photon emission computed tomography (SPECT) technique uses gamma-emitting radioisotopes and can be used to diagnose strokes, seizures, bone illnesses, and infections by gauging the blood flow and radio distribution within tissues and organs. The radioisotopes typically used in SPECT imaging are iodine-123, technetium-99m, xenon-133, thallium-201, and indium-111. This systematic review article aims to clarify and disseminate the available scientific literature focused on PET/SPECT radiotracers and to provide an overview of the conducted research within the past decade, with an additional focus on the novel radiopharmaceuticals developed for medical imaging.
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Affiliation(s)
- George Crișan
- Faculty of Physics, Babeş-Bolyai University, Str. M. Kogălniceanu 1, 400084 Cluj-Napoca, Romania; (G.C.); (N.S.M.-C.); (D.-G.T.)
- Department of Nuclear Medicine, County Clinical Hospital, Clinicilor 3-5, 400006 Cluj-Napoca, Romania;
| | | | - Diana-Gabriela Timaru
- Faculty of Physics, Babeş-Bolyai University, Str. M. Kogălniceanu 1, 400084 Cluj-Napoca, Romania; (G.C.); (N.S.M.-C.); (D.-G.T.)
| | - Gabriel Andrieș
- Department of Nuclear Medicine, County Clinical Hospital, Clinicilor 3-5, 400006 Cluj-Napoca, Romania;
| | - Călin Căinap
- The Oncology Institute “Prof. Dr. Ion Chiricuţă”, Republicii 34-36, 400015 Cluj-Napoca, Romania;
| | - Vasile Chiș
- Faculty of Physics, Babeş-Bolyai University, Str. M. Kogălniceanu 1, 400084 Cluj-Napoca, Romania; (G.C.); (N.S.M.-C.); (D.-G.T.)
- Institute for Research, Development and Innovation in Applied Natural Sciences, Babeș-Bolyai University, Str. Fântânele 30, 400327 Cluj-Napoca, Romania
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Elisei R, Agate L, Mazzarri S, Bottici V, Guidoccio F, Molinaro E, Boni G, Ferdeghini M, Mariani G. Radionuclide Therapy of Thyroid Tumors. NUCLEAR ONCOLOGY 2022:1381-1429. [DOI: 10.1007/978-3-031-05494-5_49] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Haslerud T. SPECT/CT in Neuroendrocrine Tumours. CLINICAL APPLICATIONS OF SPECT-CT 2022:95-118. [DOI: 10.1007/978-3-030-65850-2_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Queiroz CC, Machado MAD, Ximenes AAB, Pino AGS, Netto EM. Technical note: Partitioning of gated single photon emission computed tomography raw data for protocols optimization. J Appl Clin Med Phys 2021; 23:e13508. [PMID: 34918865 PMCID: PMC8906212 DOI: 10.1002/acm2.13508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 11/07/2021] [Accepted: 12/06/2021] [Indexed: 11/12/2022] Open
Abstract
PURPOSE Methodologies for optimization of SPECT image acquisition can be challenging due to imaging throughput, physiological bias, and patient comfort constraints. We evaluated a vendor-independent method for simulating lower count image acquisitions. METHODS We developed an algorithm that recombines the ECG-gated raw data into reduced counting acquisitions. We then tested the algorithm to simulate reduction of counting statistics from phantom SPECT image acquisition, which was synchronized with an ECG simulator. The datasets were reconstructed with a resolution recovery algorithm and the summed stress score (SSS) was assessed by three readers (two experts and one automatic). RESULTS The algorithm generated varying counting levels, simulating multiple examinations at the same time. The error between the expected and the simulated countings ranged from approximately 5% to 10% for the ungated simulations and 0% for the gated simulations. CONCLUSIONS The vendor-independent algorithm successfully generated lower counting statistics datasets from single-gated SPECT raw data. This method can be readily implemented for optimal SPECT research aiming to lower the injected activity and/ or to shorten the acquisition time.
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Affiliation(s)
- Cleiton Cavalcante Queiroz
- Department of Nuclear Medicine, São Rafael Hospital/ Rede D'or, Salvador, Bahia, Brazil.,Department of Nuclear Medicine, Cardio Pulmonar Hospital/ Rede D'or, Salvador, Bahia, Brazil.,Department of Nuclear Medicine, Hospital Universitario Professor Alberto Antunes/Ebserh, Maceio, Alagoas, Brazil
| | - Marcos Antonio Dorea Machado
- Department of Nuclear Medicine, São Rafael Hospital/ Rede D'or, Salvador, Bahia, Brazil.,Department of Nuclear Medicine, Cardio Pulmonar Hospital/ Rede D'or, Salvador, Bahia, Brazil.,Department of Health Technology Evaluation, Complexo Hospitalar Universitário Prof. Edgard Santos/Ebserh, Salvador, Bahia, Brazil
| | | | - Andre Gustavo Silva Pino
- Department of Nuclear Medicine, Hospital Universitario Professor Alberto Antunes/Ebserh, Maceio, Alagoas, Brazil
| | - Eduardo Martins Netto
- Infectious Disease Research Laboratory, Complexo Hospitalar Universitário Prof. Edgard Santos/Ebserh, Universidade Federal da Bahia, Salvador, Bahia, Brazil
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Cao SS, Li SY, Geng YM, Kapat K, Liu SB, Perera FH, Li Q, Terheyden H, Wu G, Che YJ, Miranda P, Zhou M. Prefabricated 3D-Printed Tissue-Engineered Bone for Mandibular Reconstruction: A Preclinical Translational Study in Primate. ACS Biomater Sci Eng 2021; 7:5727-5738. [PMID: 34808042 PMCID: PMC8672350 DOI: 10.1021/acsbiomaterials.1c00509] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
![]()
The
advent of three dimensionally (3D) printed customized bone
grafts using different biomaterials has enabled repairs of complex
bone defects in various in vivo models. However, studies related to
their clinical translations are truly limited. Herein, 3D printed
poly(lactic-co-glycolic acid)/β-tricalcium
phosphate (PLGA/TCP) and TCP scaffolds with or without recombinant
bone morphogenetic protein −2 (rhBMP-2) coating were utilized
to repair primate’s large-volume mandibular defects and compared
efficacy of prefabricated tissue-engineered bone (PTEB) over direct
implantation (without prefabrication). 18F-FDG PET/CT was
explored for real-time monitoring of bone regeneration and vascularization.
After 3-month’s prefabrication, the original 3D-architecture
of the PLGA/TCP-BMP scaffold was found to be completely lost, while
it was properly maintained in TCP-BMP scaffolds. Besides, there was
a remarkable decrease in the PLGA/TCP-BMP scaffold density and increase
in TCP-BMP scaffolds density during ectopic (within latissimus dorsi
muscle) and orthotopic (within mandibular defect) implantation, indicating
regular bone formation with TCP-BMP scaffolds. Notably, PTEB based
on TCP-BMP scaffold was successfully fabricated with pronounced effects
on bone regeneration and vascularization based on radiographic, 18F-FDG PET/CT, and histological evaluation, suggesting a promising
approach toward clinical translation.
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Affiliation(s)
- Shuai-Shuai Cao
- Department of Oral and Maxillofacial Surgery, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, China
| | - Shu-Yi Li
- Department of Oral and Maxillofacial Surgery, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, China.,Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Amsterdam Movement Science, de Boelelaan, Vrije Universiteit Amsterdam 1117, Amsterdam, The Netherlands
| | - Yuan-Ming Geng
- Department of Stomatology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
| | - Kausik Kapat
- Department of Oral and Maxillofacial Surgery, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, China
| | - Shang-Bin Liu
- Department of Oral and Maxillofacial Surgery, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, China
| | - Fidel Hugo Perera
- Department of Mechanical, Energy and Materials Engineering, University of Extremadura, Industrial Engineering School, Avda. de Elvas s/n, 06006 Badajoz, Spain
| | - Qian Li
- Hangzhou Jiuyuan Gene Engineering Co., Ltd., Hangzhou 3100018, China
| | - Hendrik Terheyden
- Department of Oral and Maxillofacial Surgery, Red Cross Hospital, Kassel 34117, Germany
| | - Gang Wu
- Department of Oral Implantology and Prosthetic Dentistry, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam 1117, The Netherlands
| | - Yue-Juan Che
- Department of Anesthesia, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Pedro Miranda
- Department of Mechanical, Energy and Materials Engineering, University of Extremadura, Industrial Engineering School, Avda. de Elvas s/n, 06006 Badajoz, Spain
| | - Miao Zhou
- Department of Oral and Maxillofacial Surgery, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, China
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Favaretto C, Talip Z, Borgna F, Grundler PV, Dellepiane G, Sommerhalder A, Zhang H, Schibli R, Braccini S, Müller C, van der Meulen NP. Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging. EJNMMI Radiopharm Chem 2021; 6:37. [PMID: 34778932 PMCID: PMC8590989 DOI: 10.1186/s41181-021-00153-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 10/26/2021] [Indexed: 11/17/2022] Open
Abstract
Background Terbium-155 [T1/2 = 5.32 d, Eγ = 87 keV (32%) 105 keV (25%)] is an interesting radionuclide suitable for single photon emission computed tomography (SPECT) imaging with potential application in the diagnosis of oncological disease. It shows similar decay characteristics to the clinically established indium-111 and would be a useful substitute for the diagnosis and prospective dosimetry with biomolecules that are afterwards labeled with therapeutic radiolanthanides and pseudo-radiolanthanides, such as lutetium-177 and yttrium-90. Moreover, terbium-155 could form part of the perfect “matched pair” with the therapeutic radionuclide terbium-161, making the concept of true radiotheragnostics a reality. The aim of this study was the investigation of the production of terbium-155 via the 155Gd(p,n)155Tb and 156Gd(p,2n)155Tb nuclear reactions and its subsequent purification, in order to obtain a final product in quantity and quality sufficient for preclinical application. The 156Gd(p,2n)155Tb nuclear reaction was performed with 72 MeV protons (degraded to ~ 23 MeV), while the 155Gd(p,n)155Tb reaction was degraded further to ~ 10 MeV, as well as performed at an 18 MeV medical cyclotron, to demonstrate its feasibility of production. Result The 156Gd(p,2n)155Tb nuclear reaction demonstrated higher production yields of up to 1.7 GBq, however, lower radionuclidic purity when compared to the final product (~ 200 MBq) of the 155Gd(p,n)155Tb nuclear reaction. In particular, other radioisotopes of terbium were produced as side products. The radiochemical purification of terbium-155 from the target material was developed to provide up to 1.0 GBq product in a small volume (~ 1 mL 0.05 M HCl), suitable for radiolabeling purposes. The high chemical purity of terbium-155 was proven by radiolabeling experiments at molar activities up to 100 MBq/nmol. SPECT/CT experiments were performed in tumor-bearing mice using [155Tb]Tb-DOTATOC. Conclusion This study demonstrated two possible production routes for high activities of terbium-155 using a cyclotron, indicating that the radionuclide is more accessible than the exclusive mass-separated method previously demonstrated. The developed radiochemical purification of terbium-155 from the target material yielded [155Tb]TbCl3 in high chemical purity. As a result, initial cell uptake investigations, as well as SPECT/CT in vivo studies with [155Tb]Tb-DOTATOC, were successfully performed, indicating that the chemical separation produced a product with suitable quality for preclinical studies. Supplementary Information The online version contains supplementary material available at 10.1186/s41181-021-00153-w.
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Affiliation(s)
- C Favaretto
- Center for Radiopharmaceutical Sciences, ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland.,Department of Chemistry and Applied Biosciences, ETH Zurich, 8093, Zurich, Switzerland
| | - Z Talip
- Center for Radiopharmaceutical Sciences, ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland
| | - F Borgna
- Center for Radiopharmaceutical Sciences, ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland
| | - P V Grundler
- Center for Radiopharmaceutical Sciences, ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland
| | - G Dellepiane
- Albert Einstein Center for Fundamental Physics (AEC), Laboratory of High Energy Physics (LHEP), University of Bern, 3012, Bern, Switzerland
| | - A Sommerhalder
- Center for Radiopharmaceutical Sciences, ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland
| | - H Zhang
- Division Large Research Facilities, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland
| | - R Schibli
- Center for Radiopharmaceutical Sciences, ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland.,Department of Chemistry and Applied Biosciences, ETH Zurich, 8093, Zurich, Switzerland
| | - S Braccini
- Albert Einstein Center for Fundamental Physics (AEC), Laboratory of High Energy Physics (LHEP), University of Bern, 3012, Bern, Switzerland
| | - C Müller
- Center for Radiopharmaceutical Sciences, ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland
| | - N P van der Meulen
- Center for Radiopharmaceutical Sciences, ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland. .,Laboratory of Radiochemistry, Paul Scherrer Institute, 5232, Villigen-PSI, Switzerland.
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The Evolution and Future of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, and Oncolytic Bacteria to the Treatment of Solid Tumors. NANOMATERIALS 2021; 11:nano11113018. [PMID: 34835785 PMCID: PMC8623458 DOI: 10.3390/nano11113018] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 10/28/2021] [Accepted: 11/01/2021] [Indexed: 02/07/2023]
Abstract
While many classes of chemotherapeutic agents exist to treat solid tumors, few can generate a lasting response without substantial off-target toxicity despite significant scientific advancements and investments. In this review, the paths of development for nanoparticles, oncolytic viruses, and oncolytic bacteria over the last 20 years of research towards clinical translation and acceptance as novel cancer therapeutics are compared. Novel nanoparticle, oncolytic virus, and oncolytic bacteria therapies all start with a common goal of accomplishing therapeutic drug activity or delivery to a specific site while avoiding off-target effects, with overlapping methodology between all three modalities. Indeed, the degree of overlap is substantial enough that breakthroughs in one therapeutic could have considerable implications on the progression of the other two. Each oncotherapeutic modality has accomplished clinical translation, successfully overcoming the potential pitfalls promising therapeutics face. However, once studies enter clinical trials, the data all but disappears, leaving pre-clinical researchers largely in the dark. Overall, the creativity, flexibility, and innovation of these modalities for solid tumor treatments are greatly encouraging, and usher in a new age of pharmaceutical development.
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Biassoni L, Privitera L. 123I-Meta-Iodobenzylguanidine Single-Photon Emission Computerized Tomography/Computerized Tomography Scintigraphy in the Management of Neuroblastoma. Indian J Nucl Med 2021; 36:293-299. [PMID: 34658554 PMCID: PMC8481844 DOI: 10.4103/ijnm.ijnm_10_21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Accepted: 01/28/2021] [Indexed: 11/04/2022] Open
Abstract
Neuroblastoma is the most common pediatric extracranial solid tumor. High-risk neuroblastoma is the most frequent presentation with an overall survival of approximately 50%. 123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy in the assessment of the primary tumor and its metastases at diagnosis and after chemotherapy is a cornerstone imaging modality. In particular, the bulk of skeletal metastatic disease evaluated with 123I-mIBG at diagnosis and the following chemotherapy has a prognostic value. Currently, single-photon emission computerized tomography/computerised tomography (SPECT/CT) is considered a fundamental part of 123I-mIBG scintigraphy. 123I-mIBG SPECT/CT is a highly specific and sensitive imaging biomarker and it has been the basis of all existing neuroblastoma trials requiring molecular imaging. The introduction of SPECT/CT has shown not only the heterogeneity of the mIBG uptake within the primary tumor but also the presence of completely mIBG nonavid metastatic lesions with mIBG-avid primary neuroblastomas. It is currently possible to semi-quantitatively assess tracer uptake with standardized uptake value, which allows a more precise evaluation of the tracer avidity and can help monitor chemotherapy response. The patchy mIBG uptake has consequences from a theranostic perspective and may partly explain the failure of some neuroblastomas to respond to 131I-mIBG molecular radiotherapy. Various positron emission tomography tracers, targeting different aspects of neuroblastoma cell biology, are being tested as possible alternatives to 123I-mIBG.
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Affiliation(s)
- Lorenzo Biassoni
- Department of Radiology, Great Ormond Street Hospital for Children, London, UK
| | - Laura Privitera
- Department of Developmental Biology and Cancer Research, UCL GOS Institute of Child Health, London, UK
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Dorraji ES, Oteiza A, Kuttner S, Martin-Armas M, Kanapathippillai P, Garbarino S, Kalda G, Scussolini M, Piana M, Fenton KA. Positron emission tomography and single photon emission computed tomography imaging of tertiary lymphoid structures during the development of lupus nephritis. Int J Immunopathol Pharmacol 2021; 35:20587384211033683. [PMID: 34344200 PMCID: PMC8351034 DOI: 10.1177/20587384211033683] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Lymphoid neogenesis occurs in tissues targeted by chronic inflammatory processes, such as infection and autoimmunity. In systemic lupus erythematosus (SLE), such structures develop within the kidneys of lupus-prone mice ((NZBXNZW)F1) and are observed in kidney biopsies taken from SLE patients with lupus nephritis (LN). The purpose of this prospective longitudinal animal study was to detect early kidney changes and tertiary lymphoid structures (TLS) using in vivo imaging. Positron emission tomography (PET) by tail vein injection of 18-F-fluoro-2-deoxy-D-glucose (18F-FDG)(PET/FDG) combined with computed tomography (CT) for anatomical localization and single photon emission computed tomography (SPECT) by intraperitoneal injection of 99mTC labeled Albumin Nanocoll (99mTC-Nanocoll) were performed on different disease stages of NZB/W mice (n = 40) and on aged matched control mice (BALB/c) (n = 20). By using one-way ANOVA analyses, we compared two different compartmental models for the quantitative measure of 18F-FDG uptake within the kidneys. Using a new five-compartment model, we observed that glomerular filtration of 18FFDG in lupus-prone mice decreased significantly by disease progression measured by anti-dsDNA Ab production and before onset of proteinuria. We could not visualize TLS within the kidneys, but we were able to visualize pancreatic TLS using 99mTC Nanocoll SPECT. Based on our findings, we conclude that the five-compartment model can be used to measure changes of FDG uptake within the kidney. However, new optimal PET/SPECT tracer administration sites together with more specific tracers in combination with magnetic resonance imaging (MRI) may make it possible to detect formation of TLS and LN before clinical manifestations.
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Affiliation(s)
- Esmaeil S Dorraji
- RNA and Molecular Pathology Research Group, Institute of Medical Biology, Faculty of Health Sciences, 8016UiT The Arctic University of Norway, Tromsø, Norway
| | - Ana Oteiza
- Nuclear Medicine and Radiation Biology Research Group, Department of Clinical Medicine, Faculty of Health Science, 8016UiT The Arctic University of Norway, Tromsø, Norway
| | - Samuel Kuttner
- Nuclear Medicine and Radiation Biology Research Group, Department of Clinical Medicine, Faculty of Health Science, 8016UiT The Arctic University of Norway, Tromsø, Norway
| | - Montserrat Martin-Armas
- Nuclear Medicine and Radiation Biology Research Group, Department of Clinical Medicine, Faculty of Health Science, 8016UiT The Arctic University of Norway, Tromsø, Norway
| | - Premasany Kanapathippillai
- RNA and Molecular Pathology Research Group, Institute of Medical Biology, Faculty of Health Sciences, 8016UiT The Arctic University of Norway, Tromsø, Norway
| | - Sara Garbarino
- Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK
| | - Gustav Kalda
- Nuclear Medicine and Radiation Biology Research Group, Department of Clinical Medicine, Faculty of Health Science, 8016UiT The Arctic University of Norway, Tromsø, Norway
| | - Mara Scussolini
- Dipartimento di Matematica, 9302Universita di Genova, Genova, Italy
| | - Michele Piana
- Dipartimento di Matematica, 9302Universita di Genova, Genova, Italy.,Dipartimento di Matematica, 9302Universita di Genova, and CNR-SPIN, Genova, Italy
| | - Kristin A Fenton
- RNA and Molecular Pathology Research Group, Institute of Medical Biology, Faculty of Health Sciences, 8016UiT The Arctic University of Norway, Tromsø, Norway
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Abstract
A growing theme in chemistry is the joining of multiple organic molecular building blocks to create functional molecules. Diverse derivatizable structures—here termed “scaffolds” comprised of “hubs”—provide the foundation for systematic covalent organization of a rich variety of building blocks. This review encompasses 30 tri- or tetra-armed molecular hubs (e.g., triazine, lysine, arenes, dyes) that are used directly or in combination to give linear, cyclic, or branched scaffolds. Each scaffold is categorized by graph theory into one of 31 trees to express the molecular connectivity and overall architecture. Rational chemistry with exacting numbers of derivatizable sites is emphasized. The incorporation of water-solubilization motifs, robust or self-immolative linkers, enzymatically cleavable groups and functional appendages affords immense (and often late-stage) diversification of the scaffolds. Altogether, 107 target molecules are reviewed along with 19 syntheses to illustrate the distinctive chemistries for creating and derivatizing scaffolds. The review covers the history of the field up through 2020, briefly touching on statistically derivatized carriers employed in immunology as counterpoints to the rationally assembled and derivatized scaffolds here, although most citations are from the past two decades. The scaffolds are used widely in fields ranging from pure chemistry to artificial photosynthesis and biomedical sciences.
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Tepelenis K, Skandalakis GP, Papathanakos G, Kefala MA, Kitsouli A, Barbouti A, Tepelenis N, Varvarousis D, Vlachos K, Kanavaros P, Kitsoulis P. Osteoid Osteoma: An Updated Review of Epidemiology, Pathogenesis, Clinical Presentation, Radiological Features, and Treatment Option. In Vivo 2021; 35:1929-1938. [PMID: 34182465 DOI: 10.21873/invivo.12459] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 04/19/2021] [Accepted: 04/20/2021] [Indexed: 12/12/2022]
Abstract
Osteoid osteoma, the third most common benign bone tumor, usually occurs in the cortex of long bones. It consists of a radiolucent nidus surrounded by reactive osteosclerosis. Generally, osteoid osteoma affects young males. Nocturnal pain that eases with salicylates or nonsteroidal anti-inflammatory drugs (NSAID) is the typical clinical presentation. Sometimes, it remains undiagnosed for a long time. Plain radiography and computed tomography are usually sufficient for the diagnosis of osteoid osteoma. Initial treatment includes salicylates and NSAID because the tumor often regresses spontaneously over 2-6 years. Surgical treatment is indicated in case of unresponsive pain to medical therapy, no tolerance of prolonged NSAID therapy due to side effects, and no willingness to activity limitations. Nowadays, minimally invasive techniques have replaced open surgery and are considered the gold standard of surgical treatment. Although cryoablation seems superior in terms of the nerve damage and immunotherapy effect, radiofrequency ablation is the preferred technique.
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Affiliation(s)
- Kostas Tepelenis
- Department of Surgery, University Hospital of Ioannina, Ioannina, Greece;
| | - Georgios P Skandalakis
- Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York City, NY, U.S.A
| | | | | | | | - Alexandra Barbouti
- Anatomy - Histology - Embryology, University of Ioannina, Ioannina, Greece
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Wang F, Chen J, Liu J, Zeng H. Cancer theranostic platforms based on injectable polymer hydrogels. Biomater Sci 2021; 9:3543-3575. [PMID: 33634800 DOI: 10.1039/d0bm02149k] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Theranostic platforms that combine therapy with diagnosis not only prevent the undesirable biological responses that may occur when these processes are conducted separately, but also allow individualized therapies for patients. Polymer hydrogels have been employed to provide well-controlled drug release and targeted therapy in theranostics, where injectable hydrogels enable non-invasive treatment and monitoring with a single injection, offering greater patient comfort and efficient therapy. Efforts have been focused on applying injectable polymer hydrogels in theranostic research and clinical use. This review highlights recent progress in the design of injectable polymer hydrogels for cancer theranostics, particularly focusing on the elements/components of theranostic hydrogels, and their cross-linking strategies, structures, and performance with regard to drug delivery/tracking. Therapeutic agents and tracking modalities that are essential components of the theranostic platforms are introduced, and the design strategies, properties and applications of the injectable hydrogels developed via two approaches, namely chemical bonds and physical interactions, are described. The theranostic functions of the platforms are highly dependent on the architecture and components employed for the construction of hydrogels. Challenges currently presented by theranostic platforms based on injectable hydrogels are identified, and prospects of acquiring more comfortable and personalized therapies are proposed.
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Affiliation(s)
- Feifei Wang
- The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510700, China. and Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada.
| | - Jingsi Chen
- Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada.
| | - Jifang Liu
- The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510700, China.
| | - Hongbo Zeng
- Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada.
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Sier VQ, van der Vorst JR, Quax PHA, de Vries MR, Zonoobi E, Vahrmeijer AL, Dekkers IA, de Geus-Oei LF, Smits AM, Cai W, Sier CFM, Goumans MJTH, Hawinkels LJAC. Endoglin/CD105-Based Imaging of Cancer and Cardiovascular Diseases: A Systematic Review. Int J Mol Sci 2021; 22:4804. [PMID: 33946583 PMCID: PMC8124553 DOI: 10.3390/ijms22094804] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 04/27/2021] [Accepted: 04/28/2021] [Indexed: 02/07/2023] Open
Abstract
Molecular imaging of pathologic lesions can improve efficient detection of cancer and cardiovascular diseases. A shared pathophysiological feature is angiogenesis, the formation of new blood vessels. Endoglin (CD105) is a coreceptor for ligands of the Transforming Growth Factor-β (TGF-β) family and is highly expressed on angiogenic endothelial cells. Therefore, endoglin-based imaging has been explored to visualize lesions of the aforementioned diseases. This systematic review highlights the progress in endoglin-based imaging of cancer, atherosclerosis, myocardial infarction, and aortic aneurysm, focusing on positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), near-infrared fluorescence (NIRF) imaging, and ultrasound imaging. PubMed was searched combining the following subjects and their respective synonyms or relevant subterms: "Endoglin", "Imaging/Image-guided surgery". In total, 59 papers were found eligible to be included: 58 reporting about preclinical animal or in vitro models and one ex vivo study in human organs. In addition to exact data extraction of imaging modality type, tumor or cardiovascular disease model, and tracer (class), outcomes were described via a narrative synthesis. Collectively, the data identify endoglin as a suitable target for intraoperative and diagnostic imaging of the neovasculature in tumors, whereas for cardiovascular diseases, the evidence remains scarce but promising.
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Affiliation(s)
- Vincent Q. Sier
- Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (V.Q.S.); (J.R.v.d.V.); (P.H.A.Q.); (M.R.d.V.); (E.Z.); (A.L.V.)
| | - Joost R. van der Vorst
- Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (V.Q.S.); (J.R.v.d.V.); (P.H.A.Q.); (M.R.d.V.); (E.Z.); (A.L.V.)
| | - Paul H. A. Quax
- Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (V.Q.S.); (J.R.v.d.V.); (P.H.A.Q.); (M.R.d.V.); (E.Z.); (A.L.V.)
| | - Margreet R. de Vries
- Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (V.Q.S.); (J.R.v.d.V.); (P.H.A.Q.); (M.R.d.V.); (E.Z.); (A.L.V.)
| | - Elham Zonoobi
- Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (V.Q.S.); (J.R.v.d.V.); (P.H.A.Q.); (M.R.d.V.); (E.Z.); (A.L.V.)
- Edinburgh Molecular Imaging Ltd. (EMI), Edinburgh EH16 4UX, UK
| | - Alexander L. Vahrmeijer
- Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (V.Q.S.); (J.R.v.d.V.); (P.H.A.Q.); (M.R.d.V.); (E.Z.); (A.L.V.)
| | - Ilona A. Dekkers
- Department of Radiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands;
| | - Lioe-Fee de Geus-Oei
- Department of Radiology, Section of Nuclear Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands;
- Biomedical Photonic Imaging Group, University of Twente, 7500 AE Enschede, The Netherlands
| | - Anke M. Smits
- Department of Cell & Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (A.M.S.); (M.J.T.H.G.)
| | - Weibo Cai
- Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, WI 53705, USA;
| | - Cornelis F. M. Sier
- Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (V.Q.S.); (J.R.v.d.V.); (P.H.A.Q.); (M.R.d.V.); (E.Z.); (A.L.V.)
- Percuros B.V., 2333 CL Leiden, The Netherlands
| | - Marie José T. H. Goumans
- Department of Cell & Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (A.M.S.); (M.J.T.H.G.)
| | - Lukas J. A. C. Hawinkels
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands;
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Ayesa SL, Schembri GP. Is 67gallium dead? A retrospective review of 67gallium imaging in a single tertiary referral centre. Nucl Med Commun 2021; 42:378-388. [PMID: 33323867 DOI: 10.1097/mnm.0000000000001342] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND [67Ga]Ga-citrate scanning has been used to investigate patients with known or suspected infection for over 50 years, continuing to maintain a clinical niche in many centres. The introduction of single photon emission tomography/computed tomography (SPECT/CT) in addition to planar imaging has improved the specificity of diagnosis. AIM To examine the experience of modern [67Ga]Ga-citrate scanning in a single tertiary referral centre, considering the diagnostic yield of the study. METHODS A retrospective audit was undertaken of 100 consecutive [67Ga]Ga-citrate scans at Royal North Shore Hospital, Sydney. Recorded information included patient demographics, clinical information/history, and primary and secondary diagnoses. Subgroup analyses included patients with a confirmed diagnosis of infection or a suspected diagnosis of infection. RESULTS The median age of patients was 68.5 years. Totally, 39/100 patients undergoing [67Ga]Ga-citrate scanning presented with a confirmed site of infection, with 2/6 patients with infective endocarditis and 5/12 patients with bacteraemia diagnosed with an additional, previously unknown, site of active infection (compared to 1/21 patients without documented bacteraemia). 61/100 patients did not have a confirmed site of infection before [67Ga]Ga-citrate scan (as per clinical history). 34/61 of these patients had a positive scan result for active infection/inflammation. Of 20 patients with a positive blood culture but no suspected site of infection, the source was identified in 9. CONCLUSION [67Ga]Ga-citrate has diagnostic value in the evaluation of complex patients with high-risk infection. High diagnostic yield is demonstrated in patients with bacteraemia with or without a confirmed site of infection, particularly when combined with SPECT/CT.
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Affiliation(s)
- Sally L Ayesa
- Department of Nuclear Medicine, Royal North Shore Hospital
- Faculty of Medicine & Health, University of Sydney, New South Wales, Australia
| | - Geoffrey P Schembri
- Department of Nuclear Medicine, Royal North Shore Hospital
- Faculty of Medicine & Health, University of Sydney, New South Wales, Australia
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Okubo K, Takeda R, Murayama S, Umezawa M, Kamimura M, Osada K, Aoki I, Soga K. Size-controlled bimodal in vivo nanoprobes as near-infrared phosphors and positive contrast agents for magnetic resonance imaging. SCIENCE AND TECHNOLOGY OF ADVANCED MATERIALS 2021; 22:160-172. [PMID: 33762891 PMCID: PMC7952065 DOI: 10.1080/14686996.2021.1887712] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/02/2021] [Accepted: 02/03/2021] [Indexed: 06/12/2023]
Abstract
Rare-earth-doped nanoparticles (NPs), such as NaGdF4 nanocrystals doped with light-emitting rare earth ions, are promising bimodal probes that allow the integration of over 1000 nm near-infrared (OTN-NIR; NIR-II/III) fluorescence imaging and magnetic resonance imaging (MRI) of live bodies. A precise control of the particle size is the key factor for achieving a high signal-to-noise ratio in both NIR fluorescence and MR images and for regulating their function in the body. In this study, size-controlled NaGdF4:Yb3+, Er3+ NPs prepared by stepwise crystal growth were used for in vivo bimodal imaging. Hexagonal NaGdF4:Yb3+,Er3+ NPs coated with poly(ethylene glycol)-poly(acrylic acid) block copolymer, with hydrodynamic diameters of 15 and 45 nm, were prepared and evaluated as bimodal NPs for OTN-NIR fluorescence imaging and MRI. Their longitudinal (T 1) and transverse (T 2) relaxation rates at the static magnetic field strength of 1.0 T, as well as their cytotoxicity towards NIH3T3 cell lines, were evaluated and compared to study the effect of size. Using these particles, blood vessel visualization was achieved by MRI, with the highest relaxometric ratio (r 1/r 2) of 0.79 reported to date for NaGdF4-based nanoprobes (r 1 = 19.78 mM-1 s-1), and by OTN-NIR fluorescence imaging. The results clearly demonstrate the potential of the size-controlled PEG-modified NaGdF4:Yb3+,Er3+ NPs as powerful 'positive' T 1-weight contrast MRI agents and OTN-NIR fluorophores.
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Affiliation(s)
- Kyohei Okubo
- Department of Materials Science and Technology, Tokyo University of Science, Tokyo, Japan
| | - Ryuta Takeda
- Department of Materials Science and Technology, Tokyo University of Science, Tokyo, Japan
| | - Shuhei Murayama
- Group of Quantum-state Controlled MRI, National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan
| | - Masakazu Umezawa
- Department of Materials Science and Technology, Tokyo University of Science, Tokyo, Japan
| | - Masao Kamimura
- Department of Materials Science and Technology, Tokyo University of Science, Tokyo, Japan
| | - Kensuke Osada
- Group of Quantum-state Controlled MRI, National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan
| | - Ichio Aoki
- Group of Quantum-state Controlled MRI, National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan
| | - Kohei Soga
- Department of Materials Science and Technology, Tokyo University of Science, Tokyo, Japan
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