|
1
|
Das S, Dey MK, Devireddy R, Gartia MR. Biomarkers in Cancer Detection, Diagnosis, and Prognosis. SENSORS (BASEL, SWITZERLAND) 2023; 24:37. [PMID: 38202898 PMCID: PMC10780704 DOI: 10.3390/s24010037] [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: 09/08/2023] [Revised: 11/27/2023] [Accepted: 12/15/2023] [Indexed: 01/12/2024]
Abstract
Biomarkers are vital in healthcare as they provide valuable insights into disease diagnosis, prognosis, treatment response, and personalized medicine. They serve as objective indicators, enabling early detection and intervention, leading to improved patient outcomes and reduced costs. Biomarkers also guide treatment decisions by predicting disease outcomes and facilitating individualized treatment plans. They play a role in monitoring disease progression, adjusting treatments, and detecting early signs of recurrence. Furthermore, biomarkers enhance drug development and clinical trials by identifying suitable patients and accelerating the approval process. In this review paper, we described a variety of biomarkers applicable for cancer detection and diagnosis, such as imaging-based diagnosis (CT, SPECT, MRI, and PET), blood-based biomarkers (proteins, genes, mRNA, and peptides), cell imaging-based diagnosis (needle biopsy and CTC), tissue imaging-based diagnosis (IHC), and genetic-based biomarkers (RNAseq, scRNAseq, and spatial transcriptomics).
Collapse
Affiliation(s)
| | | | | | - Manas Ranjan Gartia
- Department of Mechanical and Industrial Engineering, Louisiana State University, Baton Rouge, LA 70803, USA; (S.D.); (M.K.D.); (R.D.)
| |
Collapse
|
|
2
|
Krarup MMK, Fischer BM, Christensen TN. New PET Tracers: Current Knowledge and Perspectives in Lung Cancer. Semin Nucl Med 2022; 52:781-796. [PMID: 35752465 DOI: 10.1053/j.semnuclmed.2022.05.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 05/04/2022] [Indexed: 11/11/2022]
Abstract
PET/CT with the tracer 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) has improved diagnostic imaging in cancer and is routinely used for diagnosing, staging and treatment planning in lung cancer patients. However, pitfalls of [18F]FDG-PET/CT limit the use in specific settings. Additionally, lung cancer is still the leading cause of cancer associated death and has high risk of recurrence after curative treatment. These circumstances have led to the continuous search for more sensitive and specific PET tracers to optimize lung cancer diagnosis, staging, treatment planning and evaluation. The objective of this review is to present and discuss current knowledge and perspectives of new PET tracers for use in lung cancer. A literature search was performed on PubMed and clinicaltrials.gov, limited to the past decade, excluding case reports, preclinical studies and studies on established tracers such as [18F]FDG and DOTATE. The most relevant papers from the search were evaluated. Several tracers have been developed targeting specific tumor characteristics and hallmarks of cancer. A small number of tracers have been studied extensively and evaluated head-to-head with [18F]FDG-PET/CT, whereas others need further investigation and validation in larger clinical trials. At this moment, none of the tracers can replace [18F]FDG-PET/CT. However, they might serve as supplementary imaging methods to provide more knowledge about biological tumor characteristics and visualize intra- and inter-tumoral heterogeneity.
Collapse
Affiliation(s)
- Marie M K Krarup
- Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet Copehagen University Hospital, Copenhagen, Denmark.
| | - Barbara M Fischer
- Department of Clinical Medicine, Faculty of Health, Univeristy of Copenhagen (UCPH), Copenhagen, Denmark; School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom
| | - Tine N Christensen
- Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet Copehagen University Hospital, Copenhagen, Denmark
| |
Collapse
|
|
3
|
Burchardt E, Warenczak-Florczak Z, Cegła P, Piotrowski A, Cybulski Z, Burchardt W, Roszak A, Cholewiński W. Differences between [18F]FLT and [18F]FDG Uptake in PET/CT Imaging in CC Depend on Vaginal Bacteriology. Diagnostics (Basel) 2021; 12:diagnostics12010070. [PMID: 35054237 PMCID: PMC8774914 DOI: 10.3390/diagnostics12010070] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 12/27/2021] [Indexed: 11/30/2022] Open
Abstract
This study aims to investigate if vaginal bacteriology obtained prior to treatment influences the 3′-deoxy-3 18F-fluorothymidine (FLT) [18F]FLT and 2-deoxy-2-[18F]fluoro-d-glucose (2-[18F]FDG) [18F]FDG parameters in positron emission tomography (PET/CT) in cervical cancer (CC) patients. Methods: Retrospective analysis was performed on 39 women with locally advanced histologically confirmed cervical cancer who underwent dual tracer PET/CT examinations. The [18F]FLT and [18F]FDG PET parameters in the primary tumor, including SUVmax, SUVmean, MTV, heterogeneity, before radiotherapy (RT) were analyzed, depending on the bacteriology. The p-values < 0.05 were considered statistically significant. Results: In the vaginal and/or cervical smears, there were 27 (79.4%) positive results. In seven (20.6%) cases, no opportunistic pathogen growth was observed (No Bacteria Group). In positive bacteriology, eleven (32%) Gram-negative bacilli (Bacteria group 2) and fifteen (44%) Gram-positive bacteria (Bacteria group 1) were detected. Five patients with unknown results were excluded from the analysis. Data analysis shows a statistically significant difference between the SUVmax, and SUVmin values for three independent groups for the [18F]FLT. Conclusions: The lowest values of SUVmax and SUVmin for [18F]FLT are registered in Gram-negative bacteria, higher are in Gram-positive, and the absence of bacteria causes the highest [18F]FLT values.
Collapse
Affiliation(s)
- Ewa Burchardt
- Department of Radiotherapy and Oncological Gynecology, Greater Poland Cancer Center, 61-866 Poznan, Poland; (Z.W.-F.); (A.R.)
- Department of Electroradiology, University of Medical Science Poznan, 61-866 Poznan, Poland; (W.B.); (W.C.)
- Correspondence:
| | - Zaneta Warenczak-Florczak
- Department of Radiotherapy and Oncological Gynecology, Greater Poland Cancer Center, 61-866 Poznan, Poland; (Z.W.-F.); (A.R.)
- Department of Electroradiology, University of Medical Science Poznan, 61-866 Poznan, Poland; (W.B.); (W.C.)
| | - Paulina Cegła
- Department of Nuclear Medicine, Greater Poland Cancer Center, 61-866 Poznan, Poland;
| | - Adam Piotrowski
- Faculty of Physics, Adam Mickiewicz University, 61-614 Poznan, Poland;
| | - Zefiryn Cybulski
- Greater Poland Cancer Center, Microbiology Laboratorium, 61-866 Poznan, Poland;
| | - Wojciech Burchardt
- Department of Electroradiology, University of Medical Science Poznan, 61-866 Poznan, Poland; (W.B.); (W.C.)
- Department of Brachytherapy, Greater Poland Cancer Center, 61-866 Poznan, Poland
| | - Andrzej Roszak
- Department of Radiotherapy and Oncological Gynecology, Greater Poland Cancer Center, 61-866 Poznan, Poland; (Z.W.-F.); (A.R.)
- Department of Electroradiology, University of Medical Science Poznan, 61-866 Poznan, Poland; (W.B.); (W.C.)
| | - Witold Cholewiński
- Department of Electroradiology, University of Medical Science Poznan, 61-866 Poznan, Poland; (W.B.); (W.C.)
- Department of Nuclear Medicine, Greater Poland Cancer Center, 61-866 Poznan, Poland;
| |
Collapse
|
|
4
|
Goud NS, Bhattacharya A, Joshi RK, Nagaraj C, Bharath RD, Kumar P. Carbon-11: Radiochemistry and Target-Based PET Molecular Imaging Applications in Oncology, Cardiology, and Neurology. J Med Chem 2021; 64:1223-1259. [PMID: 33499603 DOI: 10.1021/acs.jmedchem.0c01053] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The positron emission tomography (PET) molecular imaging technique has gained its universal value as a remarkable tool for medical diagnosis and biomedical research. Carbon-11 is one of the promising radiotracers that can report target-specific information related to its pharmacology and physiology to understand the disease status. Currently, many of the available carbon-11 (t1/2 = 20.4 min) PET radiotracers are heterocyclic derivatives that have been synthesized using carbon-11 inserted different functional groups obtained from primary and secondary carbon-11 precursors. A spectrum of carbon-11 PET radiotracers has been developed against many of the upregulated and emerging targets for the diagnosis, prognosis, prediction, and therapy in the fields of oncology, cardiology, and neurology. This review focuses on the carbon-11 radiochemistry and various target-specific PET molecular imaging agents used in tumor, heart, brain, and neuroinflammatory disease imaging along with its associated pathology.
Collapse
Affiliation(s)
- Nerella Sridhar Goud
- Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560 029, India
| | - Ahana Bhattacharya
- Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560 029, India
| | - Raman Kumar Joshi
- Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560 029, India
| | - Chandana Nagaraj
- Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560 029, India
| | - Rose Dawn Bharath
- Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560 029, India
| | - Pardeep Kumar
- Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560 029, India
| |
Collapse
|
|
5
|
Aasen SN, Espedal H, Keunen O, Adamsen TCH, Bjerkvig R, Thorsen F. Current landscape and future perspectives in preclinical MR and PET imaging of brain metastasis. Neurooncol Adv 2021; 3:vdab151. [PMID: 34988446 PMCID: PMC8704384 DOI: 10.1093/noajnl/vdab151] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Brain metastasis (BM) is a major cause of cancer patient morbidity. Clinical magnetic resonance imaging (MRI) and positron emission tomography (PET) represent important resources to assess tumor progression and treatment responses. In preclinical research, anatomical MRI and to some extent functional MRI have frequently been used to assess tumor progression. In contrast, PET has only to a limited extent been used in animal BM research. A considerable culprit is that results from most preclinical studies have shown little impact on the implementation of new treatment strategies in the clinic. This emphasizes the need for the development of robust, high-quality preclinical imaging strategies with potential for clinical translation. This review focuses on advanced preclinical MRI and PET imaging methods for BM, describing their applications in the context of what has been done in the clinic. The strengths and shortcomings of each technology are presented, and recommendations for future directions in the development of the individual imaging modalities are suggested. Finally, we highlight recent developments in quantitative MRI and PET, the use of radiomics and multimodal imaging, and the need for a standardization of imaging technologies and protocols between preclinical centers.
Collapse
Affiliation(s)
- Synnøve Nymark Aasen
- Department of Biomedicine, University of Bergen, Bergen, Norway
- Department of Health and Functioning, Western Norway University of Applied Sciences, Bergen, Norway
| | - Heidi Espedal
- The Molecular Imaging Center, Department of Biomedicine, University of Bergen, Bergen, Norway
- Mohn Medical Imaging and Visualization Centre, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Olivier Keunen
- Translational Radiomics, Department of Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg
| | - Tom Christian Holm Adamsen
- Centre for Nuclear Medicine, Department of Radiology, Haukeland University Hospital, Bergen, Norway
- 180 °N – Bergen Tracer Development Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway
- Department of Chemistry, University of Bergen, Bergen, Norway
| | - Rolf Bjerkvig
- Department of Biomedicine, University of Bergen, Bergen, Norway
- NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg
| | - Frits Thorsen
- Department of Biomedicine, University of Bergen, Bergen, Norway
- The Molecular Imaging Center, Department of Biomedicine, University of Bergen, Bergen, Norway
- Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Key Laboratory of Brain Functional Remodeling, Shandong, Jinan, P.R. China
| |
Collapse
|
|
6
|
Pérez-García VM, Calvo GF, Bosque JJ, León-Triana O, Jiménez J, Perez-Beteta J, Belmonte-Beitia J, Valiente M, Zhu L, García-Gómez P, Sánchez-Gómez P, Hernández-San Miguel E, Hortigüela R, Azimzade Y, Molina-García D, Martinez Á, Rojas ÁA, de Mendivil AO, Vallette F, Schucht P, Murek M, Pérez-Cano M, Albillo D, Honguero Martínez AF, Jiménez Londoño GA, Arana E, García Vicente AM. Universal scaling laws rule explosive growth in human cancers. NATURE PHYSICS 2020; 16:1232-1237. [PMID: 33329756 PMCID: PMC7116451 DOI: 10.1038/s41567-020-0978-6] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly-complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings.
Collapse
Affiliation(s)
- Víctor M. Pérez-García
- Mathematical Oncology Laboratory, Universidad de Castilla-La Mancha, Spain
- Correspondence and requests for materials should be addressed to V.M. Pérez-García (>)
| | - Gabriel F. Calvo
- Mathematical Oncology Laboratory, Universidad de Castilla-La Mancha, Spain
| | - Jesús J. Bosque
- Mathematical Oncology Laboratory, Universidad de Castilla-La Mancha, Spain
| | | | - Juan Jiménez
- Mathematical Oncology Laboratory, Universidad de Castilla-La Mancha, Spain
| | | | | | - Manuel Valiente
- Brain Metastasis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
| | - Lucía Zhu
- Brain Metastasis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
| | - Pedro García-Gómez
- Brain Metastasis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
| | | | | | - Rafael Hortigüela
- Neuro-oncology Unit, Health Institute Carlos III-UFIEC, Madrid, Spain
| | | | | | - Álvaro Martinez
- Mathematical Oncology Laboratory, Universidad de Castilla-La Mancha, Spain
- Department of Mathematics, Universidad de Cádiz, Spain
| | - Ángel Acosta Rojas
- Department of Radiation Oncology, Sanchinarro University Hospital, HM Hospitales, Spain
| | | | - Francois Vallette
- Inserm U1232, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, Nantes, F-44007, France
| | | | | | - María Pérez-Cano
- Mathematical Oncology Laboratory, Universidad de Castilla-La Mancha, Spain
| | - David Albillo
- Radiology Unit, MD Anderson Cancer Center, Madrid, Spain
| | | | | | | | | |
Collapse
|
|
7
|
Yang Y, He MZ, Li T, Yang X. MRI combined with PET-CT of different tracers to improve the accuracy of glioma diagnosis: a systematic review and meta-analysis. Neurosurg Rev 2019; 42:185-195. [PMID: 28918564 PMCID: PMC6503074 DOI: 10.1007/s10143-017-0906-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 09/01/2017] [Accepted: 09/06/2017] [Indexed: 12/18/2022]
Abstract
Based on studies focusing on positron emission tomography (PET)-computed tomography (CT) combined with magnetic resonance imaging (MRI) in the diagnosis of glioma, we conducted a systematic review and meta-analysis evaluating the pros and cons and the accuracy of different examinations. PubMed and Cochrane Library were searched. The search was conducted until April 2017. Two reviewers independently conducted the literature search according to the criteria set initially. Based on the exclusion criteria, 15 articles are included in this study. Of all studies that used MRI examination, there are five involving 18F-fluorodeoxyglucose-PET, five involving 11C-methionine-PET, five involving 18F-fluoro-ethyl-tyrosine-PET, and three involving 18F-fluorothymidine-PET. Due to the limitations such as lack of data, small sample size, and unrepresentative studies, we use a non-quantitative methodology. MRI examination can provide the anatomy information of glioma more clearly. PET-CT examinations based on tumor metabolism using different tracers have more advantages in determining the degree of glioma malignancy and boundaries. However, information provided by PET-CT of different tracers is not the same. With respect to the novel hybrid MRI/PET examination equipment proposed in recent years, the combination of MRI and PET-CT can definitively improve the diagnostic accuracy of glioma.
Collapse
Affiliation(s)
- Yihan Yang
- Department of Neurosurgery, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, China
| | - Mike Z He
- Columbia University Mailman School of Public Health, New York, NY, USA
| | - Tao Li
- Department of Neurosurgery, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, China
| | - Xuejun Yang
- Department of Neurosurgery, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, China.
| |
Collapse
|
|
8
|
Zanoni L, Broccoli A, Lambertini A, Pellegrini C, Stefoni V, Lodi F, Fonti C, Nanni C, Zinzani PL, Fanti S. Role of 18F-FLT PET/CT in suspected recurrent or residual lymphoma: final results of a pilot prospective trial. Eur J Nucl Med Mol Imaging 2019; 46:1661-1671. [DOI: 10.1007/s00259-019-04323-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Accepted: 03/29/2019] [Indexed: 01/01/2023]
|
|
9
|
Molecular Imaging-Guided Radiotherapy for the Treatment of Head-and-Neck Squamous Cell Carcinoma: Does it Fulfill the Promises? Semin Radiat Oncol 2018; 28:35-45. [PMID: 29173754 DOI: 10.1016/j.semradonc.2017.08.003] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
With the routine use of intensity modulated radiation therapy for the treatment of head-and-neck squamous cell carcinoma allowing highly conformed dose distribution, there is an increasing need for refining both the selection and the delineation of gross tumor volumes (GTV). In this framework, molecular imaging with positron emission tomography and magnetic resonance imaging offers the opportunity to improve diagnostic accuracy and to integrate tumor biology mainly related to the assessment of tumor cell density, tumor hypoxia, and tumor proliferation into the treatment planning equation. Such integration, however, requires a deep comprehension of the technical and methodological issues related to image acquisition, reconstruction, and segmentation. Until now, molecular imaging has had a limited value for the selection of nodal GTV, but there are increasing evidences that both FDG positron emission tomography and diffusion-weighted magnetic resonance imaging has a potential value for the delineation of the primary tumor GTV, effecting on dose distribution. With the apprehension of the heterogeneity in tumor biology through molecular imaging, growing evidences have been collected over the years to support the concept of dose escalation/dose redistribution using a planned heterogeneous dose prescription, the so-called "dose painting" approach. Validation trials are ongoing, and in the coming years, one may expect to position the dose painting approach in the armamentarium for the treatment of patients with head-and-neck squamous cell carcinoma.
Collapse
|
|
10
|
Ponto LLB, Walsh S, Huang J, Mundt C, Thede-Reynolds K, Leonard Watkins G, Sunderland J, Acevedo M, Donovan M. Pharmacoimaging of Blood-Brain Barrier Permeable (FDG) and Impermeable (FLT) Substrates After Intranasal (IN) Administration. AAPS JOURNAL 2017; 20:15. [PMID: 29218424 DOI: 10.1208/s12248-017-0157-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 10/21/2017] [Indexed: 01/07/2023]
Abstract
To illustrate the use of imaging to quantify the transfer of materials from the nasal cavity to other anatomical compartments, specifically, transfer to the brain using the thymidine analogue, [18F]fluorothymidine (FLT), and the glucose analogue, [18F]fluorodeoxyglucose (FDG). Anesthetized rats were administered FLT or FDG by intranasal instillation (IN) or tail-vein injection (IV). PET/CT imaging was performed for up to 60 min. Volumes-of-interest (VOIs) for the olfactory bulb (OB) and the remaining brain were created on the CT and transferred to the co-registered dynamic PET. Time-activity curves (TACs) were generated and compared. The disposition patterns were successfully visualized and quantified and differences in brain distribution patterns were observed. For FDG, the concentration was substantially higher in the OB than the brain only after IN administration. For FLT, the concentration was higher in the OB than the brain after both IN and IV and higher after IN than after IV administration at all times, whereas the concentration in the brain was higher after IN than after IV administration at early times only. Approximately 50 and 9% of the IN FDG and FLT doses, respectively, remained in the nasal cavity at 20 min post-administration. The initial phase of clearance was similar for both agents (t1/2 = 2.53 and 3.36 min) but the slow clearance phase was more rapid for FLT than FDG (t1/2 = 32.1 and 85.2 min, respectively). Pharmacoimaging techniques employing PET/CT can be successfully implemented to quantitatively investigate and compare the disposition of radiolabeled agents administered by a variety of routes.
Collapse
Affiliation(s)
- Laura L Boles Ponto
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA. .,PET Imaging Center, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa, 52242, USA.
| | - Susan Walsh
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
| | - Jiangeng Huang
- College of Pharmacy, Division of Pharmaceutics and Translational Therapeutics, Iowa City, Iowa, USA.,Department of Pharmaceutics, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Christine Mundt
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.,PET Imaging Center, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa, 52242, USA
| | - Katherine Thede-Reynolds
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.,PET Imaging Center, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa, 52242, USA
| | - G Leonard Watkins
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.,PET Imaging Center, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa, 52242, USA
| | - John Sunderland
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.,PET Imaging Center, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa, 52242, USA
| | - Michael Acevedo
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
| | - Maureen Donovan
- College of Pharmacy, Division of Pharmaceutics and Translational Therapeutics, Iowa City, Iowa, USA
| |
Collapse
|
|
11
|
Clinical overview of the current state and future applications of positron emission tomography in bone and soft tissue sarcoma. Clin Transl Imaging 2017. [DOI: 10.1007/s40336-017-0236-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
|
|
12
|
Kwee TC, Gholami S, Werner TJ, Rubello D, Alavi A, Høilund-Carlsen PF. 18F-FDG, as a single imaging agent in assessing cancer, shows the ongoing biological phenomena in many domains: do we need additional tracers for clinical purposes? Nucl Med Commun 2016; 37:333-7. [PMID: 26796033 DOI: 10.1097/mnm.0000000000000478] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Affiliation(s)
- Thomas C Kwee
- aDepartment of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands bDepartment of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA cDepartment of Nuclear Medicine, PET/CT Centre, Radiology, Interventional Radiology NeuroRadiology, Medical Physics, Clinical Laboratory, Biomarkers Laboratory, Pathology, Microbiology, 'Santa Maria della Misericordia' Hospital, Rovigo, Italy dDepartment of Nuclear Medicine, Odense University Hospital eInstitute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | | | | | | | | | | |
Collapse
|
|
13
|
Intratumoral heterogeneity of 18F-FLT uptake predicts proliferation and survival in patients with newly diagnosed gliomas. Ann Nucl Med 2016; 31:46-52. [PMID: 27686469 DOI: 10.1007/s12149-016-1129-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2016] [Accepted: 09/23/2016] [Indexed: 10/20/2022]
Abstract
BACKGROUND The nucleoside analog 3'-deoxy-3'-18F-fluorothymidine (FLT) has been investigated for evaluating tumor proliferating activity in brain tumors. We evaluated FLT uptake heterogeneity using textural features from the histogram analysis in patients with newly diagnosed gliomas and examined correlation of the results with proliferative activity and patient prognosis, in comparison with the conventional PET parameters. METHODS FLT PET was investigated in 37 patients with newly diagnosed gliomas. The conventional parameters [tumor-to-contralateral normal brain tissue (T/N) ratio and metabolic tumor volume (MTV)] and textural parameters (standard deviation, skewness, kurtosis, entropy, and uniformity) were derived from FLT PET images. Linear regression analysis was used to compare PET parameters and the proliferative activity as indicated by the Ki-67 index. The associations between parameters and overall survival (OS) were tested by Cox regression analysis. RESULTS Median OS was 662 days. For the conventional parameters, linear regression analysis indicated a significant correlation between T/N ratio and Ki-67 index (p = 0.02) and MTV and Ki-67 index (p = 0.02). Among textural parameters, linear regression analysis indicated a significant correlation for kurtosis (p = 0.003), entropy (p < 0.001), and uniformity (p < 0.001) as compared to Ki-67 index, exceeding those of the conventional parameters. The results of univariate analysis suggested that skewness and kurtosis were associated with OS (p = 0.03 and 0.02, respectively). Mean survival for patients with skewness values less than 0.65 was 1462 days, compared with 917 days for those with values greater than 0.65 (p = 0.02). Mean survival for patients with kurtosis values less than 6.16 was 1616 days, compared with 882 days for those with values greater than 6.16 (p = 0.006). CONCLUSIONS Based on the results of this preliminary study in a small patient population, textural features reflecting heterogeneity on FLT PET images seem to be useful for the assessment of proliferation and for the potential prediction of survival in newly diagnosed gliomas.
Collapse
|
|
14
|
Skovgaard D, Persson M, Brandt-Larsen M, Christensen C, Madsen J, Klausen TL, Holm S, Andersen FL, Loft A, Berthelsen AK, Pappot H, Brasso K, Kroman N, Højgaard L, Kjaer A. Safety, Dosimetry, and Tumor Detection Ability of 68Ga-NOTA-AE105: First-in-Human Study of a Novel Radioligand for uPAR PET Imaging. J Nucl Med 2016; 58:379-386. [PMID: 27609788 DOI: 10.2967/jnumed.116.178970] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Accepted: 08/18/2016] [Indexed: 12/15/2022] Open
Abstract
The overexpression of urokinase-type plasminogen activator receptors (uPARs) represents an established biomarker for aggressiveness in most common malignant diseases, including breast cancer (BC), prostate cancer (PC), and urinary bladder cancer (UBC), and is therefore an important target for new cancer therapeutic and diagnostic strategies. In this study, uPAR PET imaging using a 68Ga-labeled version of the uPAR-targeting peptide (AE105) was investigated in a group of patients with BC, PC, and UBC. The aim of this first-in-human, phase I clinical trial was to investigate the safety and biodistribution in normal tissues and uptake in tumor lesions. Methods: Ten patients (6 PC, 2 BC, and 2 UBC) received a single intravenous dose of 68Ga-NOTA-AE105 (154 ± 59 MBq; range, 48-208 MBq). The biodistribution and radiation dosimetry were assessed by serial whole-body PET/CT scans (10 min, 1 h, and 2 h after injection). Safety assessment included measurements of vital signs with regular intervals during the imaging sessions and laboratory blood screening tests performed before and after injection. In a subgroup of patients, the in vivo stability of 68Ga-NOTA-AE105 was determined in collected blood and urine. PET images were visually analyzed for visible tumor uptake of 68Ga-NOTA-AE105, and SUVs were obtained from tumor lesions by manually drawing volumes of interest in the malignant tissue. Results: No adverse events or clinically detectable pharmacologic effects were found. The radioligand exhibited good in vivo stability and fast clearance from tissue compartments primarily by renal excretion. The effective dose was 0.015 mSv/MBq, leading to a radiation burden of 3 mSv when the clinical target dose of 200 MBq was used. In addition, radioligand accumulation was seen in primary tumor lesions as well as in metastases. Conclusion: This first-in-human, phase I clinical trial demonstrates the safe use and clinical potential of 68Ga-NOTA-AE105 as a new radioligand for uPAR PET imaging in cancer patients.
Collapse
Affiliation(s)
- Dorthe Skovgaard
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | | | - Malene Brandt-Larsen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Camilla Christensen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Jacob Madsen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Thomas Levin Klausen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Søren Holm
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Flemming Littrup Andersen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Annika Loft
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Anne Kiil Berthelsen
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Helle Pappot
- Department of Oncology, Rigshospitalet, Copenhagen, Denmark
| | - Klaus Brasso
- Department of Urology, Copenhagen Prostate Cancer Center, Rigshospitalet, Copenhagen, Denmark; and
| | - Niels Kroman
- Department of Plastic Surgery, Breast Surgery and Burns Treatment, Rigshospitalet, Copenhagen, Denmark
| | - Liselotte Højgaard
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| |
Collapse
|
|
15
|
A Pilot Study of 18F-FLT PET/CT in Pediatric Lymphoma. INTERNATIONAL JOURNAL OF MOLECULAR IMAGING 2016; 2016:6045894. [PMID: 27313888 PMCID: PMC4899586 DOI: 10.1155/2016/6045894] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Accepted: 05/05/2016] [Indexed: 11/17/2022]
Abstract
We performed an observational pilot study of 18F-FLT PET/CT in pediatric lymphoma. Eight patients with equivocal 18F-FDG PET/CT underwent imaging with 18F-FLT PET/CT. No immediate adverse reactions to 18F-FLT were observed. Compared to 18F-FDG, 18F-FLT uptake was significantly higher in bone marrow and liver (18F-FLT SUV 8.6 ± 0.6 and 5.0 ± 0.3, versus 18F-FDG SUV 1.9 ± 0.1 and 3.4 ± 0.7, resp., p < 0.05). In total, 15 lesions were evaluated with average 18F-FDG and 18F-FLT SUVs of 2.6 ± 0.1 and 2.0 ± 0.4, respectively. Nonspecific uptake in reactive lymph nodes and thymus was observed. Future studies to assess the clinical utility of 18F-FLT PET/CT in pediatric lymphoma are planned.
Collapse
|
|
16
|
Hoogenboom TC, Thursz M, Aboagye EO, Sharma R. Functional imaging of hepatocellular carcinoma. Hepat Oncol 2016; 3:137-153. [PMID: 30191034 DOI: 10.2217/hep-2015-0005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2015] [Accepted: 01/20/2016] [Indexed: 02/06/2023] Open
Abstract
Imaging plays a key role in the clinical management of hepatocellular carcinoma (HCC), but conventional imaging techniques have limited sensitivity in visualizing small tumors and assessing response to locoregional treatments and sorafenib. Functional imaging techniques allow visualization of organ and tumor physiology. Assessment of functional characteristics of tissue, such as metabolism, proliferation and stiffness, may overcome some of the limitations of structural imaging. In particular, novel molecular imaging agents offer a potential tool for early diagnosis of HCC, and radiomics may aid in response assessment and generate prognostic models. Further prospective research is warranted to evaluate emerging techniques and their cost-effectiveness in the context of HCC in order to improve detection and response assessment.
Collapse
Affiliation(s)
- Tim Ch Hoogenboom
- Department of Experimental Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK.,Department of Experimental Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK
| | - Mark Thursz
- Department of Hepatology, Imperial College NHS Trust, 10th Floor, Norfolk Place, St Mary's Hospital, London, UK.,Department of Hepatology, Imperial College NHS Trust, 10th Floor, Norfolk Place, St Mary's Hospital, London, UK
| | - Eric O Aboagye
- Comprehensive Cancer Imaging Centre at Imperial College, Faculty of Medicine, Imperial College London, GN1, Ground Floor, Commonwealth building, Hammersmith Campus, London, UK.,Comprehensive Cancer Imaging Centre at Imperial College, Faculty of Medicine, Imperial College London, GN1, Ground Floor, Commonwealth building, Hammersmith Campus, London, UK
| | - Rohini Sharma
- Department of Experimental Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK.,Department of Experimental Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK
| |
Collapse
|
|
17
|
Xu YP, Yang M. Advancement in treatment and diagnosis of pancreatic cancer with radiopharmaceuticals. World J Gastrointest Oncol 2016; 8:165-172. [PMID: 26909131 PMCID: PMC4753167 DOI: 10.4251/wjgo.v8.i2.165] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 09/30/2015] [Accepted: 12/18/2015] [Indexed: 02/05/2023] Open
Abstract
Pancreatic cancer (PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition, radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC.
Collapse
|
|
18
|
Sharma P, Mukherjee A. Newer positron emission tomography radiopharmaceuticals for radiotherapy planning: an overview. ANNALS OF TRANSLATIONAL MEDICINE 2016; 4:53. [PMID: 26904575 PMCID: PMC4739998 DOI: 10.3978/j.issn.2305-5839.2016.01.26] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 11/28/2015] [Accepted: 12/17/2015] [Indexed: 01/30/2023]
Abstract
Positron emission tomography-computed tomography (PET-CT) has changed cancer imaging in the last decade, for better. It can be employed for radiation treatment planning of different cancers with improved accuracy and outcomes as compared to conventional imaging methods. (18)F-fluorodeoxyglucose remains the most widely used though relatively non-specific cancer imaging PET tracer. A wide array of newer PET radiopharmaceuticals has been developed for targeted imaging of different cancers. PET-CT with such new PET radiopharmaceuticals has also been used for radiotherapy planning with encouraging results. In the present review we have briefly outlined the role of PET-CT with newer radiopharmaceuticals for radiotherapy planning and briefly reviewed the available literature in this regard.
Collapse
|
|
19
|
Wang C, Guo W, Zhou M, Zhu X, Ji D, Li W, Liu X, Tao Z, Zhang X, Zhang Y, Li J. The Predictive and Prognostic Value of Early Metabolic Response Assessed by Positron Emission Tomography in Advanced Gastric Cancer Treated with Chemotherapy. Clin Cancer Res 2015; 22:1603-10. [PMID: 26607599 DOI: 10.1158/1078-0432.ccr-14-3235] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Accepted: 10/06/2015] [Indexed: 11/16/2022]
Abstract
PURPOSE To evaluate the feasibility of early metabolic change assessed by PET in predicting clinical response to chemotherapy and investigate its prognostic value in patients with advanced gastric cancer. EXPERIMENTAL DESIGN A total of 64 patients with advanced gastric cancer were prospectively enrolled and examined by PET with (18)F-fluorodeoxyglucose (FDG) and (18)F-fluoro-3'-deoxy-3'-L-fluorothymidine (FLT) at baseline and 14 days after treatment initiation. PET findings were analyzed for the correlation with best clinical response of patients, disease control status, and survival after identifying the threshold of metabolic change percentage by ROC analysis. RESULTS For FDG-PET, the total uptake value reduction percentage (δ-SUV) of 40% was the cut-off point with the maximum of sensitivity (70%) and specificity (83%) to predict clinical responding and that of prediction for disease control status was 30%, with the highest sensitivity (58%) and specificity (100%). The δ-SUV of FLT-PET played no predictive role for clinical response (AUC = 0.62; P= 0.134) and disease control (AUC = 0.66; P= 0.157). The univariate Cox regression analysis revealed no significant prognostic impact. FDG uptake reduction in liver metastases could predict both clinical response (P= 0.010) and disease control status (P= 0.002) at thresholds of 35% and 15%, respectively. Those with greater FDG uptake reduction in liver lesions had a longer overall survival (P= 0.004). CONCLUSIONS Early metabolic change in FDG-PET might be a predictive marker for response and disease control in advanced gastric cancer. Early FDG uptake change in liver metastases might be a useful prognostic factor and needs further exploration.
Collapse
Affiliation(s)
- Chenchen Wang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Weijian Guo
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Min Zhou
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xiaodong Zhu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Dongmei Ji
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wenhua Li
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xin Liu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhonghua Tao
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiaowei Zhang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yingjian Zhang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Jin Li
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| |
Collapse
|
|
20
|
Anatomical, Physiological, and Molecular Imaging for Pancreatic Cancer: Current Clinical Use and Future Implications. BIOMED RESEARCH INTERNATIONAL 2015; 2015:269641. [PMID: 26146615 PMCID: PMC4471256 DOI: 10.1155/2015/269641] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Revised: 05/18/2015] [Accepted: 05/19/2015] [Indexed: 12/21/2022]
Abstract
Pancreatic adenocarcinoma is one of the deadliest human malignancies. Early detection is difficult and effective treatment is limited. Verifying the presence of micrometastatic dissemination and vessel invasion remains elusive, limiting radiological staging once this diagnosis is made. Diagnostic imaging provides independent tools to evaluate and characterize the biologic behavior of pancreatic cancer. Conventional anatomic imaging alone with either CT or MRI yields useful information on organ involvement but is limited in providing molecular and physiological information. Molecular imaging techniques such as PET or MRS provide information on metabolic and signaling pathways. Advanced MR sequences that target physiological parameters expand imaging options to characterize these tumors. By considering the parametric data from these three imaging approaches (anatomic, molecular, and physiological) we can better define specific tumor signatures. Such parametric characterization can provide insight into tumor metabolism, cellular density, protein expression, focal perfusion, and vascular permeability of these tumors. Radiogenomics research has already demonstrated ability to obtain information about cancer's genotype and phenotype; this is without invasive procedures or surgery. Further advances in these areas of experimental imaging hold promise to enable future clinical advances in detection and therapy of pancreatic cancer.
Collapse
|
|
21
|
Challapalli A, Barwick T, Pearson RA, Merchant S, Mauri F, Howell EC, Sumpter K, Maxwell RJ, Aboagye EO, Sharma R. 3'-Deoxy-3'-¹⁸F-fluorothymidine positron emission tomography as an early predictor of disease progression in patients with advanced and metastatic pancreatic cancer. Eur J Nucl Med Mol Imaging 2015; 42:831-40. [PMID: 25673055 DOI: 10.1007/s00259-015-3000-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Accepted: 01/16/2015] [Indexed: 12/21/2022]
Abstract
PURPOSE 3'-Deoxy-3'-(18)F-fluorothymidine (FLT) positron emission tomography (PET) has limited utility in abdominal imaging due to high physiological hepatic uptake of tracer. We evaluated FLT PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT PET/CTKSF) for early prediction of response and survival outcomes in locally advanced and metastatic pancreatic cancer patients receiving gemcitabine-based chemotherapy. METHODS Dynamic FLT PET/CT data were collected before and 3 weeks after the first cycle of chemotherapy. Changes in tumour FLT PET/CT variables were determined. The primary end point was RECIST 1.1 response on contrast-enhanced CT after 3 months of therapy. RESULTS Twenty patients were included. Visual distinction between tumours and normal pancreas was seen in FLT PETKSF images. All target lesions (>2 cm), including all primary pancreatic tumours, were visualised. Of the 11 liver metastases, 3 (<2 cm) were not visible after kinetic filtering. Of the 20 patients, 7 progressed (35%). Maximum standardised uptake value at 60 min post-injection (SUV60,max) significantly increased in patients with disease progression (p = 0.04). Receiver-operating characteristic curve analysis indicated that a threshold of SUV60,max increase of ≥ 12% resulted in sensitivity, specificity and positive predictive value (PPV) of 71, 100 and 100%, respectively [area under the curve (AUC) 0.90, p = 0.0001], to predict patients with disease progression. Changes in SUV60,max were not predictive of survival. CONCLUSION FLT PET/CT detected changes in proliferation, with early increase in SUV60,max predicting progressive disease with a high specificity and PPV. Therefore, FLT PET/CT could be used as an early response biomarker for gemcitabine-based chemotherapy, to select a poor prognostic group who may benefit from novel therapeutic agents in advanced and metastatic pancreatic cancer.
Collapse
|
|
22
|
Alam IS, Arshad MA, Nguyen QD, Aboagye EO. Radiopharmaceuticals as probes to characterize tumour tissue. Eur J Nucl Med Mol Imaging 2015; 42:537-61. [PMID: 25647074 DOI: 10.1007/s00259-014-2984-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 12/18/2014] [Indexed: 01/06/2023]
Abstract
Tumour cells exhibit several properties that allow them to grow and divide. A number of these properties are detectable by nuclear imaging methods. We discuss crucial tumour properties that can be described by current radioprobe technologies, further discuss areas of emerging radioprobe development, and finally articulate need areas that our field should aspire to develop. The review focuses largely on positron emission tomography and draws upon the seminal 'Hallmarks of Cancer' review article by Hanahan and Weinberg in 2011 placing into context the present and future roles of radiotracer imaging in characterizing tumours.
Collapse
Affiliation(s)
- Israt S Alam
- Comprehensive Cancer Imaging Centre, Imperial College London, London, W12 0NN, UK
| | | | | | | |
Collapse
|
|
23
|
Zhao F, Li M, Wang Z, Fu Z, Cui Y, Chen Z, Yu J. (18)F-Fluorothymidine PET-CT for resected malignant gliomas before radiotherapy: tumor extent according to proliferative activity compared with MRI. PLoS One 2015; 10:e0118769. [PMID: 25738617 PMCID: PMC4349865 DOI: 10.1371/journal.pone.0118769] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 01/06/2015] [Indexed: 01/10/2023] Open
Abstract
OBJECTIVE To compare the presence of post-operative residual disease by magnetic resonance imaging (MRI) and [18F]fluorothymidine (FLT)-positron emission tomography (PET)-computer tomography (CT) in patients with malignant glioma and to estimate the impact of 18F-FLT PET on the delineation of post-operative target volumes for radiotherapy (RT) planning. METHODS Nineteen patients with post-operative residual malignant gliomas were enrolled in this study. For each patient, 18F- FLT PET-CT and MRI were acquired in the same week, within 4 weeks after surgery but before the initiation of RT. The PET-CT and MRI data were co-registered based on mutual information. The residual tumor volume defined on the 18F-FLT PET (Vol-PET) was compared with that of gadolinium [Gd] enhancement on T1-weighted MRI (Vol-T1) and areas of hyperintensity on T2-weighted MRI (Vol-T2). RESULTS The mean Vol-PET (14.61 cm3) and Vol-T1 (13.60 cm3) were comparable and smaller than the mean Vol-T2 (32.93 cm3). The regions of 18F-FLT uptake exceeded the contrast enhancement and the hyperintense area on the MRI in 14 (73.68%) and 8 patients (42.11%), respectively. In 5 (26.32%) of the 19 patients, Vol-PET extended beyond 25 mm from the margin of Vol-T1; in 2 (10.53%) patients, Vol-PET extended 20 mm from the margin of Vol-T2. Vol-PET was detected up to 35 mm away from the edge of Vol-T1 and 24 mm away from the edge of Vol-T2. In 16 (84.21%) of the 19 patients, the Vol-T1 extended beyond the Vol-PET. In all of the patients, at least some of the Vol-T2 was located outside of the Vol-PET. CONCLUSIONS The volumes of post-operative residual tumor in patients with malignant glioma defined by 18F-FLT uptake on PET are not always consistent with the abnormalities shown on post-operative MRI. Incorporation of 18F-FLT-PET in tumor delineation may have the potential to improve the definition of target volume in post-operative radiotherapy.
Collapse
Affiliation(s)
- Fen Zhao
- Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China
- Key Laboratory of Radiation Oncology of Shandong Province, Shandong Cancer Hospital and Institute, Jinan, Shandong, China
| | - Minghuan Li
- Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China
- Key Laboratory of Radiation Oncology of Shandong Province, Shandong Cancer Hospital and Institute, Jinan, Shandong, China
| | - Zhiheng Wang
- Department of Radiation Oncology, Duke University Medical Center, Durham, NC, United States of America
| | - Zheng Fu
- Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China
- Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Jinan, Shandong, China
| | - Yunfeng Cui
- Department of Radiation Oncology, Duke University Medical Center, Durham, NC, United States of America
| | - Zhaoqiu Chen
- Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China
- Department of radiology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China
| | - Jinming Yu
- Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China
- Key Laboratory of Radiation Oncology of Shandong Province, Shandong Cancer Hospital and Institute, Jinan, Shandong, China
| |
Collapse
|
|
24
|
Imaging biomarkers in primary brain tumours. Eur J Nucl Med Mol Imaging 2014; 42:597-612. [PMID: 25520293 DOI: 10.1007/s00259-014-2971-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Accepted: 12/03/2014] [Indexed: 12/18/2022]
Abstract
We are getting used to referring to instrumentally detectable biological features in medical language as "imaging biomarkers". These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context.
Collapse
|
|
25
|
Ma DJ, Galanis E, Anderson SK, Schiff D, Kaufmann TJ, Peller PJ, Giannini C, Brown PD, Uhm JH, McGraw S, Jaeckle KA, Flynn PJ, Ligon KL, Buckner JC, Sarkaria JN. A phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: NCCTG N057K. Neuro Oncol 2014; 17:1261-9. [PMID: 25526733 DOI: 10.1093/neuonc/nou328] [Citation(s) in RCA: 121] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2007] [Accepted: 10/31/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The mammalian target of rapamycin (mTOR) functions within the phosphatidylinositol-3 kinase (PI3K)/Akt pathway as a critical modulator of cell survival. This clinical trial evaluated the combination of the mTOR inhibitor everolimus with conventional temozolomide (TMZ)-based chemoradiotherapy. METHODS Newly diagnosed patients with glioblastoma multiforme were eligible for this single arm, phase II study. Everolimus (70 mg/wk) was started 1 week prior to radiation and TMZ, followed by adjuvant TMZ, and continued until disease progression. The primary endpoint was overall survival at 12 months, and secondary endpoints were toxicity and time to progression. Eleven patients were imaged with 3'-deoxy-3'-(18)F-fluorothymidine ((18)FLT)-PET/CT before and after the initial 2 doses of everolimus before initiating radiation/TMZ. Imaged patients with sufficient tumor samples also underwent immunohistochemical and focused exon sequencing analysis. RESULTS This study accrued 100 evaluable patients. Fourteen percent of patients had grade 4 hematologic toxicities. Twelve percent had at least one grade 4 nonhematologic toxicity, and there was one treatment-related death. Overall survival at 12 months was 64% and median time to progression was 6.4 months. Of the patients who had (18)FLT-PET data, 4/9 had a partial response after 2 doses of everolimus. Focused exon sequencing demonstrated that (18)FLT-PET responders were less likely to have alterations within the PI3K/Akt/mTOR or tuberous sclerosis complex/neurofibromatosis type 1 pathway compared with nonresponders. CONCLUSION Combining everolimus with conventional chemoradiation had moderate toxicity. (18)FLT-PET studies suggested an initial antiproliferative effect in a genetically distinct subset of tumors, but this did not translate into an appreciable survival benefit compared with historical controls treated with conventional therapy.
Collapse
Affiliation(s)
- Daniel J Ma
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - Evanthia Galanis
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - S Keith Anderson
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - David Schiff
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - Timothy J Kaufmann
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - Patrick J Peller
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - Caterina Giannini
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - Paul D Brown
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - Joon H Uhm
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - Steven McGraw
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - Kurt A Jaeckle
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - Patrick J Flynn
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - Keith L Ligon
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - Jan C Buckner
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| | - Jann N Sarkaria
- Mayo Clinic, Rochester, Minnesota (D.J.M., E.G., T.J.K., P.J.P., C.G., P.D.B., J.H.U., J.C.B., J.N.S.); Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota (S.K.A.); University of Virginia, Charlottesville, Virginia (D.S.); MD Anderson Cancer Center, Houston, Texas (P.D.B.); Sioux Community Cancer Consortium, Sioux Falls, South Dakota (S.M.); Mayo Clinic, Jacksonville, Florida (K.A.J.); Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota (P.J.F.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (K.L.L.); Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L.)
| |
Collapse
|
|
26
|
Liu S, Paule MG, Zhang X, Newport GD, Patterson TA, Apana SM, Berridge MS, Maisha MP, Slikker W, Wang C. Positron Emission Tomography with [(18)F]FLT Revealed Sevoflurane-Induced Inhibition of Neural Progenitor Cell Expansion in vivo. Front Neurol 2014; 5:234. [PMID: 25452743 PMCID: PMC4233913 DOI: 10.3389/fneur.2014.00234] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2014] [Accepted: 10/28/2014] [Indexed: 01/10/2023] Open
Abstract
Neural progenitor cell expansion is critical for normal brain development and an appropriate response to injury. During the brain growth spurt, exposures to general anesthetics, which either block the N-methyl-d-aspartate receptor or enhance the γ-aminobutyric acid receptor type A can disturb neuronal transduction. This effect can be detrimental to brain development. Until now, the effects of anesthetic exposure on neural progenitor cell expansion in vivo had seldom been reported. Here, minimally invasive micro positron emission tomography (microPET) coupled with 3'-deoxy-3' [(18)F] fluoro-l-thymidine ([(18)F]FLT) was utilized to assess the effects of sevoflurane exposure on neural progenitor cell proliferation. FLT, a thymidine analog, is taken up by proliferating cells and phosphorylated in the cytoplasm, leading to its intracellular trapping. Intracellular retention of [(18)F]FLT, thus, represents an observable in vivo marker of cell proliferation. Here, postnatal day 7 rats (n = 11/group) were exposed to 2.5% sevoflurane or room air for 9 h. For up to 2 weeks following the exposure, standard uptake values (SUVs) for [(18)F]-FLT in the hippocampal formation were significantly attenuated in the sevoflurane-exposed rats (p < 0.0001), suggesting decreased uptake and retention of [(18)F]FLT (decreased proliferation) in these regions. Four weeks following exposure, SUVs for [(18)F]FLT were comparable in the sevoflurane-exposed rats and in controls. Co-administration of 7-nitroindazole (30 mg/kg, n = 5), a selective inhibitor of neuronal nitric oxide synthase, significantly attenuated the SUVs for [(18)F]FLT in both the air-exposed (p = 0.00006) and sevoflurane-exposed rats (p = 0.0427) in the first week following the exposure. These findings suggested that microPET in couple with [(18)F]FLT as cell proliferation marker could be used as a non-invasive modality to monitor the sevoflurane-induced inhibition of neural progenitor cell proliferation in vivo.
Collapse
Affiliation(s)
- Shuliang Liu
- Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson, AR , USA
| | - Merle G Paule
- Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson, AR , USA
| | - Xuan Zhang
- Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson, AR , USA
| | - Glenn D Newport
- Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson, AR , USA
| | - Tucker A Patterson
- Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson, AR , USA
| | | | | | - Mackean P Maisha
- Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson, AR , USA
| | - William Slikker
- Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson, AR , USA
| | - Cheng Wang
- Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson, AR , USA
| |
Collapse
|
|
27
|
Martens MH, Lambregts DMJ, Kluza E, Beets-Tan RGH. Tumor Response to Treatment: Prediction and Assessment. CURRENT RADIOLOGY REPORTS 2014. [DOI: 10.1007/s40134-014-0062-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
|
|
28
|
Sanghera B, Wong WL, Sonoda LI, Beynon G, Makris A, Woolf D, Ardeshna K. FLT PET-CT in evaluation of treatment response. Indian J Nucl Med 2014; 29:65-73. [PMID: 24761056 PMCID: PMC3996774 DOI: 10.4103/0972-3919.130274] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
PURPOSE Review published studies to investigate the value of clinical 3-deoxy-3-(18)F-fluorothymidine (FLT) positron emission tomography (PET) in predicting response to treatment. MATERIALS AND METHODS Interrogate databases to identify suitable publications between 2007 and 2013 with a minimum of five patients. Articles within the inclusion criteria were reviewed with major findings reported leading to a descriptive analysis of FLT PET in therapy response. RESULTS Lesions investigated included glioma, head and neck, esophageal, lung, breast, gastric, renal, rectal, sarcomas, germ cell, lymphomas, leukemia, and melanoma resulting in a total of 34 studies analyzed. A variety of therapies were applied and dissimilar PET protocols were widespread making direct comparison between studies challenging. Though baseline, early and late therapy scans were popular particularly in chemotherapy regimes. Most studies investigated showed significantly reduced FLT uptake during or after therapy compared with pretreatment scans. CONCLUSION Current evidence suggests FLT PET has a positive role to play in predicting therapy response especially in brain, lung, and breast cancers where good correlation with Ki-67 is observed. However, careful attention must be placed in undertaking larger clinical trials where harmonization of scanning and analysis protocols are strictly adhered to fully assess the true potential of FLT PET in predicting response to treatment.
Collapse
Affiliation(s)
- Bal Sanghera
- Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, England
| | - Wai Lup Wong
- Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, England
| | - Luke I Sonoda
- Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, England
| | - Gwen Beynon
- Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, England
| | - Andreas Makris
- Cancer Centre, Mount Vernon Hospital, Northwood, England
| | - David Woolf
- Cancer Centre, Mount Vernon Hospital, Northwood, England
| | - Kirit Ardeshna
- Cancer Centre, Mount Vernon Hospital, Northwood, England ; Department of Haematology, University College London Cancer Institute and University College Hospital, London, England
| |
Collapse
|
|
29
|
Farwell MD, Pryma DA, Mankoff DA. PET/CT imaging in cancer: current applications and future directions. Cancer 2014; 120:3433-45. [PMID: 24947987 DOI: 10.1002/cncr.28860] [Citation(s) in RCA: 142] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Revised: 05/05/2014] [Accepted: 05/05/2014] [Indexed: 12/22/2022]
Abstract
Positron emission tomography (PET) is a radiotracer imaging method that yields quantitative images of regional in vivo biology and biochemistry. PET, now used in conjunction with computed tomography (CT) in PET/CT devices, has had its greatest impact to date on cancer and is now an important part of oncologic clinical practice and translational cancer research. In this review of current applications and future directions for PET/CT in cancer, the authors first highlight the basic principles of PET followed by a discussion of the biochemistry and current clinical applications of the most commonly used PET imaging agent, (18) F-fluorodeoxyglucose (FDG). Then, emerging methods for PET imaging of other biologic processes relevant to cancer are reviewed, including cellular proliferation, tumor hypoxia, apoptosis, amino acid and cell membrane metabolism, and imaging of tumor receptors and other tumor-specific gene products. The focus of the review is on methods in current clinical practice as well as those that have been translated to patients and are currently in clinical trials.
Collapse
Affiliation(s)
- Michael D Farwell
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | | | | |
Collapse
|
|
30
|
Wondergem MJ, Herrmann K, Syrbu S, Zijlstra JM, Hoetjes N, Hoekstra OS, Cillessen SA, Moesbergen LM, Buck AK, Vose JM, Juweid ME. 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair. EJNMMI Res 2014; 4:3. [PMID: 24397937 PMCID: PMC3895783 DOI: 10.1186/2191-219x-4-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Accepted: 12/18/2013] [Indexed: 11/23/2022] Open
Abstract
Background We observed a disproportional 18 F-fluorothymidine (F-FLT) uptake in follicular lymphoma (FL) relative to its low cell proliferation. We tested the hypothesis that the ‘excess’ uptake of 18 F-FLT in FL is related to error-prone DNA repair and investigated whether this also contributes to 18 F-FLT uptake in diffuse large B cell lymphoma (DLBCL). Methods We performed immunohistochemical stainings to assess the pure DNA replication marker MIB-1 as well as markers of both DNA replication and repair like PCNA, TK-1 and RPA1 on lymph node biopsies of 27 FLs and 35 DLBCLs. In 7 FL and 15 DLBCL patients, 18 F-FLT-PET had been performed. Results 18 F-FLT uptake was lower in FL than in DLBCL (median SUVmax 5.7 vs. 8.9, p = 0,004), but the ratio of 18 F-FLT-SUVmax to percentage of MIB-1 positive cells was significantly higher in FL compared with DLBCL (p = 0.001). The median percentage of MIB-1 positive cells was 10% (range, 10% to 20%) in FL and 70% (40% to 80%) in DLBCL. In contrast, the median percentages of PCNA, TK-1 and RPA1 positive cells were 90% (range, 80 to 100), 90% (80 to 100) and 100% (80 to 100) in FL versus 90% (60 to 100), 90% (60 to 100) and 100% (80 to 100) in DLBCL, respectively. Conclusions This is the first demonstration of a striking discordance between 18 F-FLT uptake in FL and tumour cell proliferation. High expression of DNA replication and repair markers compared with the pure proliferation marker MIB-1 in FL suggests that this discordance might be due to error-prone DNA repair. While DNA repair-related 18 F-FLT uptake considerably contributes to 18 F-FLT uptake in FL, its contribution to 18 F-FLT uptake in highly proliferative DLBCL is small. This apparently high contribution of DNA repair to the 18 F-FLT signal in FL may hamper studies where 18 F-FLT is used to assess response to cytostatic therapy or to distinguish between FL and transformed lymphoma.
Collapse
Affiliation(s)
- Marielle J Wondergem
- Department of Haematology, VU University Medical Center (VUMC), De Boelelaan 1117, Amsterdam 1081 HV, The Netherlands.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Karroum O, Mignion L, Kengen J, Karmani L, Levêque P, Danhier P, Magat J, Bol A, Labar D, Grégoire V, Bouzin C, Feron O, Gallez B, Jordan BF. Multimodal imaging of tumor response to sorafenib combined with radiation therapy: comparison between diffusion-weighted MRI, choline spectroscopy and 18F-FLT PET imaging. CONTRAST MEDIA & MOLECULAR IMAGING 2013; 8:274-80. [PMID: 23606431 DOI: 10.1002/cmmi.1525] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2012] [Revised: 11/08/2012] [Accepted: 11/29/2012] [Indexed: 12/12/2022]
Abstract
The purpose of this study was to determine the value of different imaging modalities, that is, magnetic resonance imaging/spectroscopy (MRI/MRS) and positron emission tomography (PET), to assess early tumor response to sorafenib with or without radiotherapy. Diffusion-weighted (DW)-MRI, choline (1)H MRS at 11.7 T, and (18)F-FLT PET imaging were used to image fibrosarcoma (FSaII) tumor-bearing mice over time. The imaging markers were compared with apoptosis cell death and cell proliferation measurements assessed by histology. Anti-proliferative effects of sorafenib were evidenced by (1)H MRS and (18)F-FLT PET after 2 days of treatment with sorafenib, with no additional effect of the combination with radiation therapy, results that are in agreement with Ki67 staining. Apparent diffusion coefficient calculated using DW-MRI was not modified after 2 days of treatment with sorafenib, but showed significant increase 24 h after 2 days of sorafenib treatment combined with consecutive irradiation. The three imaging markers were able to show early tumor response as soon as 24 h after treatment initiation, with choline MRS and (18)F-FLT being sensitive to sorafenib in monotherapy as well as in combined therapy with irradiation, whereas DW-MRI was only sensitive to the combination of sorafenib with radiotherapy.
Collapse
Affiliation(s)
- Oussama Karroum
- Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Université Catholique de Louvain, Belgium, Avenue Mounier 73, B-1200 Brussels, Belgium
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Dehdashti F, Grigsby PW, Myerson RJ, Nalbantoglu I, Ma C, Siegel BA. Positron emission tomography with [(18)F]-3'-deoxy-3'fluorothymidine (FLT) as a predictor of outcome in patients with locally advanced resectable rectal cancer: a pilot study. Mol Imaging Biol 2013; 15:106-13. [PMID: 22684813 DOI: 10.1007/s11307-012-0566-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE This pilot study was performed to evaluate whether tumor uptake of (18)F-labeled 3'-deoxy-3'fluorothymidine (FLT), a proliferative radiotracer, at baseline and early during therapy, is predictive of outcome in locally advanced rectal cancer. PROCEDURES Fourteen patients underwent positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and FLT before therapy and PET with FLT approximately 2 weeks after initiating neoadjuvant chemoradiotherapy. FLT and FDG uptake were evaluated qualitatively and by maximum standardized uptake value (SUV(max)). Tumor FLT and FDG uptake were correlated with disease-free survival (DFS). RESULTS Thirteen patients underwent surgery after therapy, one died before surgery with progressive disease. FDG-PET/computed tomography detected regional lymph node metastases in five and FLT-PET was positive in one. High pretherapy FDG uptake (SUV(max) ≥ 14.3), low during-therapy FLT uptake (SUV(max) < 2.2), and high percentage change in FLT uptake (≥60 %) were predictive of improved DFS (p < 0.05 for all three values). CONCLUSION Pretherapy FDG uptake, during-therapy FLT uptake, and percentage change in FLT uptake were equally predictive of DFS.
Collapse
Affiliation(s)
- Farrokh Dehdashti
- Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
| | | | | | | | | | | |
Collapse
|
|
33
|
Wang R, Zhu H, Chen Y, Li C, Li F, Shen Z, Tian J, Yu L, Xu B. Standardized uptake value based evaluation of lymphoma by FDG and FLT PET/CT. Hematol Oncol 2013; 32:126-32. [PMID: 23996464 DOI: 10.1002/hon.2093] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2013] [Revised: 07/05/2013] [Accepted: 07/30/2013] [Indexed: 11/10/2022]
Affiliation(s)
- Ruimin Wang
- Department of Nuclear Medicine; Chinese PLA General Hospital; Beijing China
| | - Haiyan Zhu
- Department of Hematology; Chinese PLA General Hospital; Beijing China
| | - Yingmao Chen
- Department of Nuclear Medicine; Chinese PLA General Hospital; Beijing China
| | - Can Li
- Department of Nuclear Medicine; Chinese PLA General Hospital; Beijing China
| | - Fei Li
- Department of Hematology; Chinese PLA General Hospital; Beijing China
| | - Zhihui Shen
- Department of Nuclear Medicine; Chinese PLA General Hospital; Beijing China
| | - Jiahe Tian
- Department of Nuclear Medicine; Chinese PLA General Hospital; Beijing China
| | - Li Yu
- Department of Hematology; Chinese PLA General Hospital; Beijing China
| | - Baixuan Xu
- Department of Nuclear Medicine; Chinese PLA General Hospital; Beijing China
| |
Collapse
|
|
34
|
Murakami M, Zhao S, Zhao Y, Yu W, Fatema CN, Nishijima KI, Yamasaki M, Takiguchi M, Tamaki N, Kuge Y. Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model. Oncol Lett 2013; 6:667-672. [PMID: 24137387 PMCID: PMC3789029 DOI: 10.3892/ol.2013.1459] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Accepted: 06/19/2013] [Indexed: 01/30/2023] Open
Abstract
An early identification of the tumor response to sorafenib treatment is indispensable for selecting optimal personalized treatment strategies. However, at present, no reliable predictors are clinically available. 18F-fluorothymidine (18F-FLT) positron emission tomography (PET) is used to assess tumor proliferation, since the FLT uptake level reflects thymidine kinase-1 (TK-1) activity. Thus, the present study determined whether FLT was able to evaluate the early tumor response to sorafenib treatment in a human renal cell carcinoma (RCC; A498) xenograft in comparison with the tumor proliferation marker, Ki-67. Mice bearing A498 tumors were assigned to the control and sorafenib-treated groups and the tumor volume was measured every day. [Methyl-3H(N)]-3'-fluoro-3'-deoxythymidine (3H-FLT) was injected 2 h prior to the sacrifice of the mice on days three and seven following the treatment. 3H-FLT autoradiography (ARG) and Ki-67 immunohistochemistry (IHC) were performed using adjacent tumor sections. In the visual assessment, the intratumoral 3H-FLT uptake level diffusely increased following the treatment, while no significant changes were observed in Ki-67 IHC. The intratumoral 3H-FLT uptake levels significantly increased by 2.7- and 2.6-fold on days three and seven following the treatment, while the tumor volume and Ki-67 index did not significantly change. Thus, an increased FLT uptake level was demonstrated following the treatment, which may indicate the suppression of thymidylate synthase (TS) and the compensatory upregulation of TK-1 activity by sorafenib.
Collapse
Affiliation(s)
- Masahiro Murakami
- Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan ; Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-8638, Japan
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Berwouts D, Olteanu LAM, Duprez F, Vercauteren T, De Gersem W, De Neve W, Van de Wiele C, Madani I. Three-phase adaptive dose-painting-by-numbers for head-and-neck cancer: initial results of the phase I clinical trial. Radiother Oncol 2013; 107:310-6. [PMID: 23647760 DOI: 10.1016/j.radonc.2013.04.002] [Citation(s) in RCA: 103] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2012] [Revised: 03/12/2013] [Accepted: 04/01/2013] [Indexed: 10/26/2022]
Abstract
PURPOSE To evaluate feasibility of using deformable image co-registration in three-phase adaptive dose-painting-by-numbers (DPBN) for head-and-neck cancer and to report dosimetrical data and preliminary clinical results. MATERIAL AND METHODS Between November 2010 and October 2011, 10 patients with non-metastatic head-and-neck cancer enrolled in this phase I clinical trial where treatment was adapted every ten fractions. Each patient was treated with three DPBN plans based on: a pretreatment 18[F]-FDG-PET scan (phase I: fractions 1-10), a per-treatment 18[F]-FDG-PET/CT scan acquired after 8 fractions (phase II: fractions 11-20) and a per-treatment 18[F]-FDG-PET/CT scan acquired after 18 fractions (phase III: fractions 21-30). A median prescription dose to the dose-painted target was 70.2 Gy (fractions 1-30) and to elective neck was 40 Gy (fractions 1-20). Deformable image co-registration was used for automatic region-of-interest propagation and dose summation of the three treatment plans. RESULTS All patients (all men, median age 68, range 48-74 years) completed treatment without any break or acute G≥4 toxicity. Target volume reductions (mean (range)) between pre-treatment CT and CT on the last day of treatment were 72.3% (57.9-98.4) and 46.3% (11.0-73.1) for GTV and PTV(high_dose), respectively. Acute G3 toxicity was limited to dysphagia in 3/10 patients and mucositis in 2/10 patients; none of the patients lost ≥20% weight. At median follow-up of 13, range 7-22 months, 9 patients did not have evidence of disease. CONCLUSIONS Three-phase adaptive 18[F]-FDG-PET-guided dose painting by numbers using currently available tools is feasible. Irradiation of smaller target volumes might have contributed to mild acute toxicity with no measurable decrease in tumor response.
Collapse
Affiliation(s)
- Dieter Berwouts
- Department of Radiotherapy, Ghent University Hospital, Ghent, Belgium.
| | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Cervino AR, Burei M, Mansi L, Evangelista L. Molecular pathways and molecular imaging in breast cancer: an update. Nucl Med Biol 2013; 40:581-91. [PMID: 23602603 DOI: 10.1016/j.nucmedbio.2013.03.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Revised: 03/13/2013] [Accepted: 03/15/2013] [Indexed: 02/05/2023]
Abstract
Breast cancer is a heterogenic cancer being characterized by a variability of somatic mutations and in particular by different receptor expressions, such as estrogen, progesterone and human epidermal receptor. These phenotype characteristics play a crucial role in determining tumour response to various chemotherapies and other treatments and in the development of resistance to therapies. Positron emission tomography (PET) as a nuclear medicine technique, has recently demonstrated the advantages in determining the severity of disease and in evaluating the efficacy of treatments in a variety of neoplasm, including breast cancer. Because this procedure is able to pinpoint molecular activity within the body, it offers the potential to identify disease in its earliest stages as well as a patient's immediate response to therapeutic interventions in a non-invasive way. In this paper we performed an extended view about the correlation between molecular factors of breast cancer and PET tracers; in particular, we focalized our attention on their possible advantages in terms of 1) early detection of primary or recurrent cancer; 2) as a guide for target therapies and 3) for the evaluation of response to specific and now-available molecular treatments.
Collapse
Affiliation(s)
- Anna Rita Cervino
- Radiotherapy and Nuclear Medicine Unit, Istituto Oncologico Veneto IOV-IRCCS, Via Gattamelata, 64 35128 Padova, Italy
| | | | | | | |
Collapse
|
|
37
|
|
|
38
|
Diagnostic and prognostic application of positron emission tomography in breast imaging: emerging uses and the role of PET in monitoring treatment response. Breast Cancer Res Treat 2013; 138:331-46. [PMID: 23504108 DOI: 10.1007/s10549-013-2451-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Accepted: 02/18/2013] [Indexed: 12/22/2022]
Abstract
Positron emission tomography (PET) is an imaging modality that using radiotracers, permits real-time dynamic monitoring of biologic processes such as cell metabolic behavior and proliferation, and has proven useful as a research tool for understanding tumor biology. While it does not have a well-defined role in breast cancer for the purposes of screening, diagnosis, or prognosis, emerging PET technologies and uses could expand the applications of PET in breast cancer. Positron emission mammography may provide an alternative adjunct imaging modality for the screening and diagnosis of high-risk patients unable to tolerate MRI. The development of radiotracers with the ability to measure hormonal activity could provide a non-invasive way to assess hormone receptor status and functionality. Finally, the role of PET technologies in monitoring early treatment response may prove particularly useful to research involving new therapeutic interventions.
Collapse
|
|
39
|
Chang AJ, Sohn R, Lu ZH, Arbeit JM, Lapi SE. Detection of rapalog-mediated therapeutic response in renal cancer xenografts using ⁶⁴Cu-bevacizumab immunoPET. PLoS One 2013; 8:e58949. [PMID: 23516584 PMCID: PMC3597567 DOI: 10.1371/journal.pone.0058949] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2012] [Accepted: 02/11/2013] [Indexed: 11/19/2022] Open
Abstract
The importance of neovascularization for primary and metastatic tumor growth fostered numerous clinical trials of angiogenesis inhibitors either alone or in combination with conventional antineoplastic therapies. One challenge with the use of molecularly targeted agents has been the disconnection between size reduction and tumor biologic behavior, either when the drug is efficacious or when tumor resistance emerges. Here, we report the synthesis and characterization of (64)Cu-NOTA-bevacizumab as a PET imaging agent for imaging intratumoral VEGF content in vivo. (64)Cu-NOTA-bevacizumab avidly accumulated in 786-O renal carcinoma xenografts with lower levels in host organs. RAD001 (everolimus) markedly attenuated (64)Cu-NOTA-bevacizumab accumulation within 786-O renal carcinoma xenografts. Tumor tissue and cellular molecular analysis validated PET imaging, demonstrating decreases in total and secreted VEGF content and VEGFR2 activation. Notably, (64)Cu-NOTA-bevacizumab PET imaging was concordant with the growth arrest of RAD001 tumors. These data suggest that immunoPET targeting of angiogenic factors such as VEGF could be a new class of surrogate markers complementing the RECIST criteria in patients receiving molecularly targeted therapies.
Collapse
MESH Headings
- Animals
- Antibodies, Monoclonal, Humanized/chemistry
- Antibodies, Monoclonal, Humanized/metabolism
- Antibodies, Monoclonal, Humanized/pharmacokinetics
- Bevacizumab
- Cell Line, Tumor
- Cell Transformation, Neoplastic
- Copper Radioisotopes
- Everolimus
- Heterocyclic Compounds/chemistry
- Heterocyclic Compounds, 1-Ring
- Humans
- Immunoconjugates
- Kidney Neoplasms/blood supply
- Kidney Neoplasms/diagnostic imaging
- Kidney Neoplasms/pathology
- Kidney Neoplasms/therapy
- Mice
- Neovascularization, Pathologic
- Phosphorylation/drug effects
- Positron-Emission Tomography
- Sirolimus/analogs & derivatives
- Sirolimus/chemistry
- Sirolimus/pharmacology
- Treatment Outcome
- Vascular Endothelial Growth Factor A/metabolism
Collapse
Affiliation(s)
- Albert J. Chang
- Department of Radiation Oncology, Washington University, St. Louis, Missouri, United States of America
- Department of Radiology, Washington University, St. Louis, Missouri, United States of America
| | - Rebecca Sohn
- Urology Division, Department of Surgery, Washington University, St. Louis, Missouri, United States of America
| | - Zhi Hong Lu
- Urology Division, Department of Surgery, Washington University, St. Louis, Missouri, United States of America
| | - Jeffrey M. Arbeit
- Urology Division, Department of Surgery, Washington University, St. Louis, Missouri, United States of America
- Siteman Cancer Center, St. Louis, Missouri, United States of America
- * E-mail: (SEL); (JMA)
| | - Suzanne E. Lapi
- Department of Radiology, Washington University, St. Louis, Missouri, United States of America
- Siteman Cancer Center, St. Louis, Missouri, United States of America
- * E-mail: (SEL); (JMA)
| |
Collapse
|
|
40
|
Evaluation of 3'-deoxy-3'-[18F]-fluorothymidine (18F-FLT) kinetics correlated with thymidine kinase-1 expression and cell proliferation in newly diagnosed gliomas. Eur J Nucl Med Mol Imaging 2012; 40:175-85. [PMID: 23229746 DOI: 10.1007/s00259-012-2275-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2012] [Accepted: 10/04/2012] [Indexed: 10/27/2022]
Abstract
PURPOSE The thymidine analog 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) has been developed as a positron emission tomography (PET) tracer to assess the proliferation activity of tumors in vivo. The present study investigated the relationship between the kinetic parameters of (18)F-FLT in vivo and thymidine kinase-1 (TK-1) expression and cell proliferation rate in vitro, and blood-brain barrier (BBB) breakdown in human brain gliomas. METHODS A total of 21 patients with newly diagnosed gliomas were examined by (18)F-FLT PET kinetic analysis. Maximum standardized uptake value (SUVmax) and tumor-to-normal (T/N) ratio of (18)F-FLT in the tumor and (18)F-FLT kinetic parameters in the corresponding contralateral region were determined. The expression levels of TK-1 protein and mRNA were determined by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR), respectively, using surgical specimens. The cell proliferation rate of the tumor was determined in terms of the Ki-67 labeling index. BBB breakdown was evaluated on MR images with contrast enhancement. RESULTS (18)F-FLT SUVmax and T/N ratio were significantly correlated with the influx rate constant (K (1); P = 0.001 and P < 0.001, respectively), but not with the phosphorylation rate constant (k (3)). IHC and real-time PCR studies demonstrated a significant correlation between K (1) and TK-1 mRNA expression (P = 0.001), but not between k (3) and TK-1 protein and mRNA expression. Linear regression analysis revealed a significant correlation between K (1) and the Ki-67 index (P = 0.003), but not between k (3) and the Ki-67 index. TK-1 mRNA expression was significantly correlated with the Ki-67 index (P = 0.009). (18)F-FLT SUVmax and T/N ratio were significantly correlated with BBB breakdown evaluated by contrast enhancement in MR images (P = 0.003 and P = 0.011, respectively). CONCLUSION These results indicate that (18)F-FLT uptake in the tumor is significantly related to transport through the disrupted BBB, but not through phosphorylation activity. Although the tissue TK-1 expression reflects tumor proliferation activity, the phosphorylation rate constant k (3) determined by (18)F-FLT PET kinetic analysis does not accurately reflect TK-1 expression in the tissue and should not be used as a surrogate biomarker of cell proliferation activity in human brain gliomas.
Collapse
|
|
41
|
Yamamoto Y, Ono Y, Aga F, Kawai N, Kudomi N, Nishiyama Y. Correlation of 18F-FLT uptake with tumor grade and Ki-67 immunohistochemistry in patients with newly diagnosed and recurrent gliomas. J Nucl Med 2012; 53:1911-5. [PMID: 23081994 DOI: 10.2967/jnumed.112.104729] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
UNLABELLED We evaluated 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) uptake in patients with newly diagnosed and recurrent gliomas and correlated the results with tumor grade and proliferative activity. METHODS (18)F-FLT PET was investigated retrospectively in 56 patients, including 36 with newly diagnosed gliomas and 20 with recurrent gliomas. The standardized uptake values for tumor and normal contralateral hemisphere were calculated, and the tumor-to-normal (T/N) ratio was determined. Tumor grading and proliferative activity were estimated in tissue specimens. RESULTS There was a significant difference in T/N ratio among different grades of newly diagnosed gliomas and between low- and high-grade newly diagnosed and recurrent gliomas. (18)F-FLT uptake correlated more strongly with the proliferative activity in newly diagnosed gliomas than in recurrent gliomas. CONCLUSION (18)F-FLT PET seems to be useful in the noninvasive assessment of grade and proliferation in gliomas, especially newly diagnosed gliomas.
Collapse
Affiliation(s)
- Yuka Yamamoto
- Department of Radiology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
| | | | | | | | | | | |
Collapse
|
|
42
|
Idema AJ, Hoffmann AL, Boogaarts HD, Troost EG, Wesseling P, Heerschap A, van der Graaf WT, Grotenhuis JA, Oyen WJ. 3′-Deoxy-3′-18F-Fluorothymidine PET–Derived Proliferative Volume Predicts Overall Survival in High-Grade Glioma Patients. J Nucl Med 2012; 53:1904-10. [DOI: 10.2967/jnumed.112.105544] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
|
|
43
|
Predictive value of 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography/computed tomography for outcome of carbon ion radiotherapy in patients with head and neck mucosal malignant melanoma. Ann Nucl Med 2012; 27:1-10. [DOI: 10.1007/s12149-012-0652-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2012] [Accepted: 08/13/2012] [Indexed: 02/03/2023]
|
|
44
|
Abstract
Patient management in oncology increasingly relies on imaging for diagnosis, response assessment, and follow-up. The clinical availability of combined functional/anatomical imaging modalities, which integrate the benefits of visualizing tumor biology with those of high-resolution structural imaging, revolutionized clinical management of oncologic patients. Conventional high-resolution anatomical imaging modalities such as computed tomography (CT) and MRI excel at providing details on lesion location, size, morphology, and structural changes to adjacent tissues; however, these modalities provide little insight into tumor physiology. With the increasing focus on molecularly targeted therapies, imaging radiolabeled compounds with PET and single-photon emission tomography (SPECT) is often carried out to provide insight into a tumor's biological functions and its surrounding microenvironment. Despite their high sensitivity and specificity, PET and SPECT alone are substantially limited by low spatial resolution and inability to provide anatomical detail. Integrating SPECT or PET with a modality capable of providing these (i.e. CT or MR) maximizes their separate strengths and provides anatomical localization of physiological processes with detailed visualization of a tumor's structure. The availability of multimodality (hybrid) imaging with PET/CT, SPECT/CT, and PET/MR improves our ability to characterize lesions and affect treatment decisions and patient management. We have just begun to exploit the truly synergistic capabilities of multimodality imaging. Continued advances in the development of instrumentation and imaging agents will improve our ability to noninvasively characterize disease processes. This review will discuss the evolution of hybrid imaging technology and provide examples of its current and potential future clinical uses.
Collapse
|
|
45
|
Alkonyi B, Chugani HT, Muzik O, Chugani DC, Sundaram SK, Kupsky WJ, Batista CE, Juhász C. Increased L-[1-11 C] leucine uptake in the leptomeningeal angioma of sturge-weber syndrome: a PET study. J Neuroimaging 2012; 22:177-83. [PMID: 21223431 PMCID: PMC3135745 DOI: 10.1111/j.1552-6569.2010.00565.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND AND PURPOSE We used L-[1-(11) C]leucine (LEU) positron emission tomography (PET) to measure amino acid uptake in children with Sturge-Weber syndrome (SWS), and to relate amino acid uptake measures with glucose metabolism. METHODS LEU and 2-deoxy-2[(18) F]fluoro-D-glucose (FDG) PET were performed in 7 children (age: 5 months-13 years) with unilateral SWS. Asymmetries of LEU uptake in the posterior brain region, underlying the angioma and in frontal cortex, were measured and correlated with glucose hypometabolism. Kinetic analysis of LEU uptake was performed in 4 patients. RESULTS Increased LEU standard uptake value (SUV, mean: 15.1%) was found in the angioma region in 6 patients, and smaller increases in LEU SUV (11.5%) were seen in frontal cortex in 4 of the 6 patients, despite normal glucose metabolism in frontal regions. High LEU SUV was due to both increased tracer transport (3/4 patients) and high protein synthesis rates (2/4). FDG SUV asymmetries in the angioma region were inversely related to LEU SUV asymmetries (r=-.83, P= .042). CONCLUSIONS Increased amino acid uptake in the angioma region and also in less affected frontal regions may provide a marker of pathological mechanisms contributing to chronic brain damage in children with SWS.
Collapse
Affiliation(s)
- Bálint Alkonyi
- Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA
- PET Center, Children’s Hospital of Michigan, Detroit, MI, USA
| | - Harry T. Chugani
- Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA
- Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA
- PET Center, Children’s Hospital of Michigan, Detroit, MI, USA
| | - Otto Muzik
- Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA
- PET Center, Children’s Hospital of Michigan, Detroit, MI, USA
| | - Diane C. Chugani
- Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA
- PET Center, Children’s Hospital of Michigan, Detroit, MI, USA
| | - Senthil K. Sundaram
- Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA
- Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA
- PET Center, Children’s Hospital of Michigan, Detroit, MI, USA
| | - William J. Kupsky
- Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Carlos E. Batista
- Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA
- PET Center, Children’s Hospital of Michigan, Detroit, MI, USA
| | - Csaba Juhász
- Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA
- Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA
- PET Center, Children’s Hospital of Michigan, Detroit, MI, USA
| |
Collapse
|
|
46
|
Miller J, Doss M, McQuillen R, Shaller CC, Tolner B, Yu JQ, Chester K, Robinson MK. Impact of expression system on the function of the C6.5 diabody PET radiotracer. Tumour Biol 2012; 33:617-27. [PMID: 22383295 DOI: 10.1007/s13277-012-0361-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2011] [Accepted: 02/13/2012] [Indexed: 02/07/2023] Open
Abstract
The ability of engineered antibodies to rapidly and selectively target tumors that express their target antigen makes them well suited for use as radioimaging tracers. The combination of molecular size and bivalent nature makes diabody molecules a particularly promising structure for use as radiotracers for diagnostic imaging. Previous data have demonstrated that the anti-HER2 C6.5 diabody (C6.5db) is an effective radiotracer in preclinical models of HER2-positive cancer. The aim of this study was to evaluate the impact on radiotracer performance, associated with expressing the C6.5db in the Pichia pastoris (P-C6.5db) system as compared to Escherichia coli (E. C6.5db). Glycosylation of P-C6.5db led to faster blood clearance and lower overall tumor uptake than seen with E. coli-produced C6.5db. However, P-C6.5db achieved high tumor/background ratios that are critical for effective imaging. Dosimetry measurements determined in this study for both (124)I-P-C6.5db and (124)I-E-C6.5db suggest that they are equivalent to other radiotracers currently being administered to patients.
Collapse
Affiliation(s)
- Joshua Miller
- Developmental Therapeutics Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA
| | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma. Blood 2012; 119:4597-607. [PMID: 22383795 DOI: 10.1182/blood-2011-10-388298] [Citation(s) in RCA: 245] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Mantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new treatment strategies. The associated t(11:14) translocation results in enhanced cyclin D1 expression and cyclin D1-dependent kinase activity to promote cell-cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and 3-deoxy-3[(18)F]fluorothymidine (FLT) positron emission tomography (PET) to study tumor metabolism and proliferation, respectively, in concert with pre- and on-treatment lymph node biopsies to assess retinoblastoma protein (Rb) phosphorylation and markers of proliferation and apoptosis. Substantial reductions in the summed FLT-PET maximal standard uptake value (SUV(max)), as well as in Rb phosphorylation and Ki-67 expression, occurred after 3 weeks in most patients, with significant correlations among these end points. Five patients achieved progression-free survival time of > 1 year (range, 14.9-30.1+ months), with 1 complete and 2 partial responses (18% objective response rate; 90% confidence interval, 5%-40%). These patients demonstrated > 70%, > 90%, and ≥ 87.5% reductions in summed FLT SUV(max) and expression of phospho-Rb and Ki67, respectively, parameters necessary but not sufficient for long-term disease control. The results of the present study confirm CDK4/6 inhibition by PD0332991 at a well-tolerated dose and schedule and suggest clinical benefit in a subset of MCL patients. This study is registered at www.clinicaltrials.gov under identifier NCT00420056.
Collapse
|
|
48
|
Vriens D, Disselhorst JA, Oyen WJG, de Geus-Oei LF, Visser EP. Quantitative assessment of heterogeneity in tumor metabolism using FDG-PET. Int J Radiat Oncol Biol Phys 2012; 82:e725-31. [PMID: 22330998 DOI: 10.1016/j.ijrobp.2011.11.039] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2011] [Revised: 11/02/2011] [Accepted: 11/14/2011] [Indexed: 02/07/2023]
Abstract
PURPOSE [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) images are usually quantitatively analyzed in "whole-tumor" volumes of interest. Also parameters determined with dynamic PET acquisitions, such as the Patlak glucose metabolic rate (MR(glc)) and pharmacokinetic rate constants of two-tissue compartment modeling, are most often derived per lesion. We propose segmentation of tumors to determine tumor heterogeneity, potentially useful for dose-painting in radiotherapy and elucidating mechanisms of FDG uptake. METHODS AND MATERIALS In 41 patients with 104 lesions, dynamic FDG-PET was performed. On MR(glc) images, tumors were segmented in quartiles of background subtracted maximum MR(glc) (0%-25%, 25%-50%, 50%-75%, and 75%-100%). Pharmacokinetic analysis was performed using an irreversible two-tissue compartment model in the three segments with highest MR(glc) to determine the rate constants of FDG metabolism. RESULTS From the highest to the lowest quartile, significant decreases of uptake (K(1)), washout (k(2)), and phosphorylation (k(3)) rate constants were seen with significant increases in tissue blood volume fraction (V(b)). CONCLUSIONS Tumor regions with highest MR(glc) are characterized by high cellular uptake and phosphorylation rate constants with relatively low blood volume fractions. In regions with less metabolic activity, the blood volume fraction increases and cellular uptake, washout, and phosphorylation rate constants decrease. These results support the hypothesis that regional tumor glucose phosphorylation rate is not dependent on the transport of nutrients (i.e., FDG) to the tumor.
Collapse
Affiliation(s)
- Dennis Vriens
- Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
| | | | | | | | | |
Collapse
|
|
49
|
Tunariu N, Kaye SB, Desouza NM. Functional imaging: what evidence is there for its utility in clinical trials of targeted therapies? Br J Cancer 2012; 106:619-28. [PMID: 22281664 PMCID: PMC3322943 DOI: 10.1038/bjc.2011.579] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Key issues in early clinical trials of targeted agents include the determination of target inhibition, rational patient selection based on pre-treatment tumour characteristics, and assessment of tumour response in the absence of actual shrinkage. There is accumulating evidence that functional imaging using advanced techniques such as dynamic contrast enhanced (DCE)-magnetic resonance imaging (MRI), DCE-computerised tomography (CT) and DCE-ultrasound, diffusion weighted-MRI, magnetic resonance spectroscopy and positron emission tomography-CT using various labelled radioactive tracers has the potential to address all three. This article reviews this evidence with examples from trials using targeted agents with established clinical efficacy and summarises the clinical utility of the various techniques. We therefore recommend that input from specialist radiologists is sought at the early stages of trial design, in order to ensure that functional imaging is incorporated appropriately for the agent under study. There is an urgent need to strengthen the evidence base for these techniques as they evolve, and to ensure standardisation of the methodology.
Collapse
Affiliation(s)
- N Tunariu
- Section of Clinical Magnetic Resonance, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, UK.
| | | | | |
Collapse
|
|
50
|
Sze DY, Iagaru AH, Gambhir SS, De Haan HA, Reid TR. Response to Intra-Arterial Oncolytic Virotherapy with the Herpes Virus NV1020 Evaluated by [18F]Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography. Hum Gene Ther 2012; 23:91-7. [DOI: 10.1089/hum.2011.141] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Affiliation(s)
- Daniel Y. Sze
- Division of Interventional Radiology, Stanford University School of Medicine, Stanford, CA 94305
| | - Andrei H. Iagaru
- Molecular Imaging Program, Division of Nuclear Medicine, Stanford University School of Medicine, Stanford, CA 94305
| | - Sanjiv S. Gambhir
- Molecular Imaging Program, Division of Nuclear Medicine, Stanford University School of Medicine, Stanford, CA 94305
| | | | - Tony R. Reid
- Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093
| |
Collapse
|