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Sun L, Meng C, Zhang Z, Luo Y, Yang Z, Yao H. Opportunities and challenges of indocyanine green in gastrointestinal cancers for intraoperative and nano-medicine application. Cancer Nanotechnol 2024; 15:12. [DOI: 10.1186/s12645-024-00251-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 01/24/2024] [Indexed: 01/12/2025] Open
Abstract
AbstractThe morbidity and mortality of gastrointestinal tumours remain high worldwide. Surgical resection is currently the most critical radical therapeutic schedule, while postoperative complications and sentinel lymph node (SLN) identification are closely related to the outcome. Indocyanine green (ICG)-mediated fluorescence imaging is increasingly being used in gastrointestinal surgery. It has been embraced by various surgical disciplines as a potential method to improve lymph node detection and enhance surgical field visualization. ICG can passively concentrate in SLN because of enhanced permeation and retention effects. After excitation by near-infrared light devices, SLN can display higher intensity fluorescence, helping visualization for better lymph node dissection. In addition, visual assessment of intestinal blood flow through ICG may reduce the incidence of anastomotic leakage. Although it has good clinical application, ICG-imaging still faces some problems, such as a higher false-negative rate, poorly targeted biodistribution, and lower fluorescence contrast, due to the lack of active tumour targeting. Thus, different ICG-coupled nanoparticles with inherent characteristics or functional modification-enhanced SLN identification features for gastrointestinal cancers bring benefit through active tumour targeting, superior tumour-background ratio, and high resolution. Nano-ICG combined with potential substances, including enhanced imaging contrast and/or combination therapy (chemotherapy, targeted therapy, immunotherapy, etc.), have been packaged and accumulated in the tumour area through active targeting for multimodal imaging and treatment. In this review, we outline the intraoperative application and possible future nanodirections of ICG in gastrointestinal cancer. The prospects and challenges of nano-ICG diagnostic and therapeutic methods in clinical applications are also discussed.
Graphical Abstract
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Ammirati CA, Arezzo A, Gaetani C, Strazzarino GA, Faletti R, Bergamasco L, Barisone F, Fonio P, Morino M. Can we apply the concept of sentinel lymph node in rectal cancer surgery? MINIM INVASIV THER 2024:1-7. [PMID: 39295076 DOI: 10.1080/13645706.2024.2404046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 08/08/2024] [Indexed: 09/21/2024]
Abstract
INTRODUCTION Colorectal cancer remains one of the most common causes of cancer-related mortality worldwide, and lymph node staging is crucial in the diagnostic and therapeutic process. Sentinel lymph nodes are the first involved in this process, but their validity in colorectal surgery has not yet been established. Following the emergence of new imaging instrumentation, some authors have attempted to propose different techniques for lymph node identification. However, a clear pattern of mesorectal lymph node distribution relative to the primary lesion site has yet to be defined. MATERIAL AND METHODS Our analysis retrospectively reviewed suspicious mesorectal pathological lymph nodes on pre-operative magnetic resonance imaging (MRI) of rectal cancer patients, in order to assess the distribution patterns of possible tumour-related rectal lymph nodes. Mesorectal space was subdivided into quadrants and levels, and morphological features and distances from the lymph node to the primary rectal tumour were recorded. RESULTS Two hundred and fifty-five mesorectal lymph nodes distributed among 60 patients were collected. Results show that in 92.1% of cases, nodes were distributed in the same mesorectal quadrant as the rectal primary tumour, and in 88.5% of cases, they were found at the same level as the rectal primary tumour. CONCLUSIONS Although a clear node distribution pattern was not established, these results may suggest at least a lymphatic drainage preference lane, worthy of further investigation.
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Affiliation(s)
| | - Alberto Arezzo
- Department of Surgical Sciences, University of Turin, Turin, Italy
| | - Clara Gaetani
- Department of Surgical Sciences, University of Turin, Turin, Italy
| | | | - Riccardo Faletti
- Department of Surgical Sciences, University of Turin, Turin, Italy
| | - Laura Bergamasco
- Department of Surgical Sciences, University of Turin, Turin, Italy
| | | | - Paolo Fonio
- Department of Surgical Sciences, University of Turin, Turin, Italy
| | - Mario Morino
- Department of Surgical Sciences, University of Turin, Turin, Italy
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Zhang X, Yan Z, Meng Z, Li N, Jia Q, Shen Y, Ji Y. Radionuclide 131I-labeled albumin-indocyanine green nanoparticles for synergistic combined radio-photothermal therapy of anaplastic thyroid cancer. Front Oncol 2022; 12:889284. [PMID: 35957867 PMCID: PMC9358776 DOI: 10.3389/fonc.2022.889284] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 06/27/2022] [Indexed: 11/17/2022] Open
Abstract
Objectives Anaplastic thyroid cancer (ATC) cells cannot retain the radionuclide iodine 131 (131I) for treatment due to the inability to uptake iodine. This study investigated the feasibility of combining radionuclides with photothermal agents in the diagnosis and treatment of ATC. Methods 131I was labeled on human serum albumin (HSA) by the standard chloramine T method. 131I-HSA and indocyanine green (ICG) were non-covalently bound by a simple stirring to obtain 131I-HSA-ICG nanoparticles. Characterizations were performed in vitro. The cytotoxicity and imaging ability were investigated by cell/in vivo experiments. The radio-photothermal therapy efficacy of the nanoparticles was evaluated at the cellular and in vivo levels. Results The synthesized nanoparticles had a suitable size (25–45 nm) and objective biosafety. Under the irradiation of near-IR light, the photothermal conversion efficiency of the nanoparticles could reach 24.25%. In vivo fluorescence imaging and single-photon emission CT (SPECT)/CT imaging in small animals confirmed that I-HSA-ICG/131I-HSA-ICG nanoparticles could stay in tumor tissues for 4–6 days. Compared with other control groups, 131I-HSA-ICG nanoparticles had the most significant ablation effect on tumor cells under the irradiation of an 808-nm laser. Conclusions In summary, 131I-HSA-ICG nanoparticles could successfully perform dual-modality imaging and treatment of ATC, which provides a new direction for the future treatment of iodine-refractory thyroid cancer.
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Picchetto A, Diana M, Swanström LL, Magliocca FM, Pronio A, Choppin E, Rocca SL, Marescaux J, D'Ambrosio G. Upstaging nodal status in colorectal cancer using ex vivo fluorescence sentinel lymph node mapping: preliminary results. MINIM INVASIV THER 2022; 31:223-229. [PMID: 32734804 DOI: 10.1080/13645706.2020.1798464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Accepted: 06/26/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Sentinel lymph node (SLN) mapping using near-infrared fluorescence (NIRF) imaging is a recent technique to improve nodal staging in several tumors. The presence of colorectal cancer (CRC) micro-metastases has recently been defined as N1 disease and no longer as N1mi, determining the need for adjuvant chemotherapy. In CRC, the reported rate of SLN micro-metastases detected by ultrastaging techniques is as high as 30%. The aim of this prospective study is to report the preliminary results of the sensitivity analysis of NIRF imaging for ex vivo SLN mapping and the research of micro-metastases in CRC, in patients with node-negative disease (NND). MATERIAL AND METHODS On the specimen of 22 CRC patients, 1 mL of ICG (5 mg/mL) was injected submucosally around the tumor to identify SLNs. NND SLNs were further investigated with ultrastaging techniques. RESULTS Three-hundred and sixty-three lymph nodes were retrieved (59 SLNs; mean per case: 2.7). The detection, sensitivity and false-negative rate were 100%, 100% and 0% respectively. Ultrastaging investigations showed no micro-metastases in the NND SLNs. CONCLUSIONS The ex vivo SLN fluorescence-based detection in CRC was confirmed to be easy to perform and reliable. In this preliminary results report of an ongoing study, the SLN assay was congruent with the nodal status, as confirmed by histological investigations.
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Affiliation(s)
- Andrea Picchetto
- General and Colorectal Surgery Division, Department of Cardiothoracic, Vascular Surgery and Organ Transplantation, Policlinico Umberto I University Hospital, Sapienza University of Rome, Rome, Italy
| | - Michele Diana
- IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France
- IRCAD, Research Institute against Cancer of the Digestive System, Strasbourg, France
| | - Lee L Swanström
- IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France
| | - Fabio Massimo Magliocca
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Policlinico Umberto I University Hospital, Rome, Italy
| | - Annamaria Pronio
- General and Colorectal Surgery Division, Department of Cardiothoracic, Vascular Surgery and Organ Transplantation, Policlinico Umberto I University Hospital, Sapienza University of Rome, Rome, Italy
| | - Eleonore Choppin
- General and Colorectal Surgery Division, Department of Cardiothoracic, Vascular Surgery and Organ Transplantation, Policlinico Umberto I University Hospital, Sapienza University of Rome, Rome, Italy
| | - Stefania La Rocca
- General and Colorectal Surgery Division, Department of Cardiothoracic, Vascular Surgery and Organ Transplantation, Policlinico Umberto I University Hospital, Sapienza University of Rome, Rome, Italy
| | - Jacques Marescaux
- IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France
- IRCAD, Research Institute against Cancer of the Digestive System, Strasbourg, France
| | - Giancarlo D'Ambrosio
- General and Colorectal Surgery Division, Department of Cardiothoracic, Vascular Surgery and Organ Transplantation, Policlinico Umberto I University Hospital, Sapienza University of Rome, Rome, Italy
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Galema HA, Meijer RPJ, Lauwerends LJ, Verhoef C, Burggraaf J, Vahrmeijer AL, Hutteman M, Keereweer S, Hilling DE. Fluorescence-guided surgery in colorectal cancer; A review on clinical results and future perspectives. Eur J Surg Oncol 2021; 48:810-821. [PMID: 34657780 DOI: 10.1016/j.ejso.2021.10.005] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 10/07/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Colorectal cancer is the fourth most diagnosed malignancy worldwide and surgery is one of the cornerstones of the treatment strategy. Near-infrared (NIR) fluorescence imaging is a new and upcoming technique, which uses an NIR fluorescent agent combined with a specialised camera that can detect light in the NIR range. It aims for more precise surgery with improved oncological outcomes and a reduction in complications by improving discrimination between different structures. METHODS A systematic search was conducted in the Embase, Medline and Cochrane databases with search terms corresponding to 'fluorescence-guided surgery', 'colorectal surgery', and 'colorectal cancer' to identify all relevant trials. RESULTS The following clinical applications of fluorescence guided surgery for colorectal cancer were identified and discussed: (1) tumour imaging, (2) sentinel lymph node imaging, (3) imaging of distant metastases, (4) imaging of vital structures, (5) imaging of perfusion. Both experimental and FDA/EMA approved fluorescent agents are debated. Furthermore, promising future modalities are discussed. CONCLUSION Fluorescence-guided surgery for colorectal cancer is a rapidly evolving field. The first studies show additional value of this technique regarding change in surgical management. Future trials should focus on patient related outcomes such as complication rates, disease free survival, and overall survival.
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Affiliation(s)
- Hidde A Galema
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands; Department of Otorhinolaryngology, Head and Neck Surgery, Erasmus MC Cancer Institute, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands
| | - Ruben P J Meijer
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands; Centre for Human Drug Research, Zernikedreef 8, 2333, CL, Leiden, the Netherlands
| | - Lorraine J Lauwerends
- Department of Otorhinolaryngology, Head and Neck Surgery, Erasmus MC Cancer Institute, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands
| | - Jacobus Burggraaf
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands; Centre for Human Drug Research, Zernikedreef 8, 2333, CL, Leiden, the Netherlands
| | - Alexander L Vahrmeijer
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands
| | - Merlijn Hutteman
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands
| | - Stijn Keereweer
- Department of Otorhinolaryngology, Head and Neck Surgery, Erasmus MC Cancer Institute, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands
| | - Denise E Hilling
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Doctor Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands; Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, the Netherlands.
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Martínez-López E, Martínez-Pérez A, Navarro-Martínez S, Sebastián-Tomás JC, de'Angelis N, García-Granero E. Real-time fluorescence image-guided gastrointestinal oncologic surgery: Towards a new era. World J Gastrointest Oncol 2021; 13:1029-1042. [PMID: 34616510 PMCID: PMC8465438 DOI: 10.4251/wjgo.v13.i9.1029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 06/14/2021] [Accepted: 07/27/2021] [Indexed: 02/06/2023] Open
Abstract
Technological improvements are crucial in the evolution of surgery. Real-time fluorescence-guided surgery (FGS) has spread worldwide, mainly because of its usefulness during the intraoperative decision-making processes. The success of any gastrointestinal oncologic resection is based on the anatomical identification of the primary tumor and its regional lymph nodes. FGS allows also to evaluate the blood perfusion at the gastrointestinal stumps after colorectal or esophageal resections. Therefore, a reduction on the anastomotic leak rates has been postulated as one of the foreseeable benefits provided by the use of FGS in these procedures. Although the use of fluorescence in lymph node detection was initially described in breast cancer surgery, the technique is currently applied in gastric or splenic flexure cancers, as they both present complex and variable lymphatic drainages. FGS allows also to perform intraoperative lymphograms or sentinel lymph node biopsies. New applications of FGS are being developed to assist in the detection of peritoneal metastases or in the evaluation of the tumor resection margins. The present review aims to provide a general overview of the current status of real-time FGS in gastrointestinal oncologic surgery. We put a special focus on the different applications of FGS, discussing the main findings and limitations found in the contemporary literature and also the promising near future applications.
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Affiliation(s)
- Elías Martínez-López
- Department of Surgery, University of Valencia, Valencia 46010, Spain
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia 46017, Spain
| | - Aleix Martínez-Pérez
- Faculty of Health Sciences, Valencian International University, Valencia 46002, Spain
- Minimally Invasive and Robotic Digestive Surgery Unit, Miulli Hospital, Acquaviva delle Fonti 70021, Italy
| | - Sergio Navarro-Martínez
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia 46017, Spain
| | - Juan Carlos Sebastián-Tomás
- Department of Surgery, University of Valencia, Valencia 46010, Spain
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia 46017, Spain
| | - Nicola de'Angelis
- Minimally Invasive and Robotic Digestive Surgery Unit, Miulli Hospital, Acquaviva delle Fonti 70021, Italy
| | - Eduardo García-Granero
- Department of Surgery, University of Valencia, Valencia 46010, Spain
- Department of General and Digestive Surgery, Hospital Universitario y Politécnico La Fe, Valencia 46026, Spain
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Son GM, Ahn HM, Lee IY, Ha GW. Multifunctional Indocyanine Green Applications for Fluorescence-Guided Laparoscopic Colorectal Surgery. Ann Coloproctol 2021; 37:133-140. [PMID: 34102813 PMCID: PMC8273708 DOI: 10.3393/ac.2021.05.07] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 05/07/2021] [Indexed: 12/17/2022] Open
Abstract
Indocyanine green (ICG) could be applied for multiple functions such as fluorescent tumor localization, fluorescence lymph node mapping (FLNM), and intraoperative angiography in colorectal cancer surgery. With the near-infrared (NIR) systems, colonoscopic ICG tattooing can be used to define the early colorectal cancer that cannot be easily distinguished through the serosal surface. The lymphatic pathways can be visualized under the NIR system when ICG is injected through the submucosal or subserosal layer around the tumor. Intraoperative ICG angiography can be applied to find a favorable perfusion segment before the colon transection. Although all fluorescence functions are considered essential steps in image-guided surgery, it is difficult to perform multifunctional ICG applications in a single surgical procedure at once because complex protocols could interfere with each other. Therefore, we review the multifunctional ICG applications for fluorescent tumor localization, FLNM, and ICG angiography. We also discuss the optimal protocol for fluorescence-guided colorectal surgery.
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Affiliation(s)
- Gyung Mo Son
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea.,Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.,Medical Research Center, Pusan National University School of Medicine, Yangsan, Korea
| | - Hong-Min Ahn
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - In Young Lee
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.,Medical Research Center, Pusan National University School of Medicine, Yangsan, Korea
| | - Gi Won Ha
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
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Baart VM, Deken MM, Bordo MW, Bhairosingh SS, Salvatori DCF, Hyun H, Henary M, Choi HS, Sier CFM, Kuppen PJK, van Scheltinga AGTT, March TL, Valentijn ARPM, Frangioni JV, Vahrmeijer AL. Small Molecules for Multi-Wavelength Near-Infrared Fluorescent Mapping of Regional and Sentinel Lymph Nodes in Colorectal Cancer Staging. Front Oncol 2020; 10:586112. [PMID: 33392081 PMCID: PMC7774022 DOI: 10.3389/fonc.2020.586112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 11/09/2020] [Indexed: 02/06/2023] Open
Abstract
Assessing lymph node (LN) status during tumor resection is fundamental for the staging of colorectal cancer. Current guidelines require a minimum of 12 LNs to be harvested during resection and ultra-staging regional lymph nodes by sentinel lymph node (SLN) assessment is being extensively investigated. The current study presents novel near-infrared (NIR) fluorescent dyes for simultaneous pan lymph node (PanLN; regional) and SLN mapping. PanLN-Forte was intravenously injected in mice and assessed for accumulation in regional LNs. SLN800 was injected intradermally in mice, after which the collection and retention of fluorescence in SLNs were measured using indocyanine green (ICG) and its precursor, SLN700, as references. LNs in the cervical, inguinal, jejunal, iliac, and thoracic basins could clearly be distinguished after a low dose intravenous injection of PanLN-Forte. Background fluorescence was significantly lower compared to the parent compound ZW800-3A (p < 0.001). SLN700 and SLN800 specifically targeted SLNs with fluorescence being retained over 40-fold longer than the current clinically used agent ICG. Using SLN700 and SLN800, absolute fluorescence in SLN was at least 10 times higher than ICG in second-tier nodes, even at 1 hour post-injection. Histologically, the fluorescent signal localized in the LN medulla (PanLN-Forte) or sinus entry (SLN700/SLN800). PanLN-Forte and SLN800 appear to be optimal for real-time NIR fluorescence imaging of regional and SLNs, respectively.
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Affiliation(s)
- Victor M Baart
- Department of Surgery, Leiden University Medical Center, Leiden, Netherlands
| | - Marion M Deken
- Department of Surgery, Leiden University Medical Center, Leiden, Netherlands
| | | | | | - Daniela C F Salvatori
- Central Laboratory Animal Facility, Leiden University Medical Center, Leiden, Netherlands.,Anatomy and Physiology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands
| | - Hoon Hyun
- Department of Biomedical Sciences, Chonnam National University Medical School, Gwanju, South Korea
| | - Maged Henary
- Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, United States
| | - Hak Soo Choi
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - Cornelis F M Sier
- Department of Surgery, Leiden University Medical Center, Leiden, Netherlands
| | - Peter J K Kuppen
- Department of Surgery, Leiden University Medical Center, Leiden, Netherlands
| | | | - Taryn L March
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands
| | - Adrianus R P M Valentijn
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands
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Advances in image enhancement for sarcoma surgery. Cancer Lett 2020; 483:1-11. [PMID: 32247870 DOI: 10.1016/j.canlet.2020.03.029] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 03/19/2020] [Accepted: 03/29/2020] [Indexed: 12/12/2022]
Abstract
The recurrence rate of soft tissue and bone sarcomas strongly correlates to the status of the surgical margin after excision, yet excessive removal of tissue may lead to distinct, otherwise avoidable morbidity. Therefore, adequate margination of sarcomas both pre- and intra-operatively is a clinical necessity that has not yet fully been met. Current guidance for soft-tissue sarcomas recommends an ultrasound scan followed by magnetic resonance imaging (MRI). For bone sarcomas, two plane radiographs are required, followed similarly by an MRI scan. The introduction of more precise imaging modalities may reduce the morbidity associated with sarcoma surgery; the PET-CT and PET-MRI approaches in particular demonstrating high clinical efficacy. Despite advancements in the accuracy in pre-operative imaging, translation of an image to surgical margins is difficult, regularly resulting in wider resection margins than required. For soft tissue sarcomas there is currently no standard technique for image guided resections, while for bone sarcomas fluoroscopy may be used, however margins are not easily discernible during the surgical procedure. Near infra-red (NIR) fluorescence guided surgery offers an intra-operative modality through which complete tumour resection with adequate tumour-free margins may be achieved, while simultaneously minimising surgical morbidity. NIR imaging presents a potentially valuable adjunct to sarcoma surgery. Early reports indicate that it may be able to provide the surgeon with helpful information on anatomy, perfusion, lymphatic drainage, tumour margins and metastases. The use of NIR fluorochromes have also been demonstrated to be well tolerated by patients. However, prior to widespread implementation, studies related to cost-effectiveness and the development of protocols are essential. Nevertheless, NIR imaging may become ubiquitous in the future, carrying the potential to transform the surgical management of sarcoma.
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Ankersmit M, Bonjer HJ, Hannink G, Schoonmade LJ, van der Pas MHGM, Meijerink WJHJ. Near-infrared fluorescence imaging for sentinel lymph node identification in colon cancer: a prospective single-center study and systematic review with meta-analysis. Tech Coloproctol 2019; 23:1113-1126. [PMID: 31741099 PMCID: PMC6890578 DOI: 10.1007/s10151-019-02107-6] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Accepted: 10/26/2019] [Indexed: 12/12/2022]
Abstract
Background Near-infrared (NIR) fluorescence imaging has the potential to overcome the current drawbacks of sentinel lymph node mapping (SLNM) in colon cancer. Our aim was to provide an overview of current SLNM performance and of factors influencing successful sentinel lymph node (SLN) identification using NIR fluorescence imaging in colon cancer. Methods A systematic review and meta-analysis was conducted to identify currently used methods and results. Additionally, we performed a single-center study using indocyanine green (ICG) as SLNM dye in colon cancer patients scheduled for a laparoscopic colectomy. SLNs were analyzed with conventional hematoxylin-and-eosin staining and additionally with serial sectioning and immunohistochemistry (extended histopathological assessment). A true-positive procedure was defined as a tumor-positive SLN either by conventional hematoxylin-and-eosin staining or by extended histopathological assessment, independently of regional lymph node status. SLN procedures were determined to be true negatives if SLNs and regional lymph nodes revealed no metastases after conventional and advanced histopathology. SLN procedures yielding tumor-negative SLNs in combination with tumor-positive regional lymph nodes were classified as false negatives. Sensitivity, negative predictive value and detection rate were calculated. Results This systematic review and meta-analysis included 8 studies describing 227 SLN procedures. A pooled sensitivity of 0.63 (95% CI 0.51–0.74), negative predictive value 0.81 (95% CI 0.73–0.86) and detection rate of 0.94 (95% CI 0.85–0.97) were found. Upstaging as a result of extended histopathological assessment was 0.15 (95% CI 0.07–0.25). In our single-center study, we included 30 patients. Five false-negative SLNs were identified, resulting in a sensitivity of 44% and negative predictive value of 80%, with a detection rate of 89.7%. Eight patients had lymph node metastases, in three cases detected after extended pathological assessment, resulting in an upstaging of 13% (3 of 23 patients with negative nodes by conventional hematoxylin and eosin staining). Conclusions Several anatomical and technical difficulties make SLNM with NIR fluorescence imaging in colon cancer particularly challenging when compared to other types of cancer. As a consequence, reports of SLNM accuracy vary widely. Future studies should try to standardize the SLNM procedure and focus on early-stage colon tumors, validation of tracer composition, injection mode and improvement of real-time optical guidance. Electronic supplementary material The online version of this article (10.1007/s10151-019-02107-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- M Ankersmit
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC-Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.
| | - H J Bonjer
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC-Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands
| | - G Hannink
- Department of Operating Rooms and MITeC Technology Center, Radboud University Medical Center, Nijmegen, The Netherlands
| | - L J Schoonmade
- Medical Library, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | | | - W J H J Meijerink
- Department of Operating Rooms and MITeC Technology Center, Radboud University Medical Center, Nijmegen, The Netherlands
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Jung JS, Jo D, Jo G, Hyun H. Near-Infrared Contrast Agents for Bone-Targeted Imaging. Tissue Eng Regen Med 2019; 16:443-450. [PMID: 31624700 DOI: 10.1007/s13770-019-00208-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 07/16/2019] [Accepted: 07/17/2019] [Indexed: 01/21/2023] Open
Abstract
Background For the bone-specific imaging, a structure-inherent targeting of bone tissue recently has been reported a new strategy based on incorporation of targeting moieties into the chemical structure of near-infrared (NIR) contrast agents, while conventional methods require covalent conjugation of bone-targeting ligands to NIR contrast agents. This will be a new approach for bone-targeted imaging by using the bifunctional NIR contrast agents. Methods The goal of this review is to provide an overview of the recent advances in optical imaging of bone tissue, highlighting the structure-inherent targeting by developing NIR contrast agents without the need for a bone-targeting ligand such as bisphosphonates. Results A series of iminodiacetated and phosphonated NIR contrast agents for the structure-inherent targeting of bone tissue showed excellent bone-targeting ability in vivo without non-specific binding. Additionally, the phosphonated NIR contrast agents could be useful in the diagnosis of bone metastasis. Conclusion By developing bone-targeted NIR contrast agents, optical imaging of bone tissue makes it very attractive for preclinical studies of bone growth or real-time fluorescence guided surgery resulting in high potential to shift the clinical paradigms.
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Affiliation(s)
- Jin Seok Jung
- Department of Biomedical Sciences, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju, 61469 South Korea
| | - Danbi Jo
- Department of Biomedical Sciences, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju, 61469 South Korea
| | - Gayoung Jo
- Department of Biomedical Sciences, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju, 61469 South Korea
| | - Hoon Hyun
- Department of Biomedical Sciences, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju, 61469 South Korea
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12
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Katagiri W, Lee JH, Tétrault M, Kang H, Jeong S, Evans CL, Yokomizo S, Santos S, Jones C, Hu S, Fakhri GE, Tsukada K, Choi HS, Kashiwagi S. Real-Time Imaging of Vaccine Biodistribution Using Zwitterionic NIR Nanoparticles. Adv Healthc Mater 2019; 8:e1900035. [PMID: 31165556 DOI: 10.1002/adhm.201900035] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 05/06/2019] [Indexed: 12/16/2022]
Abstract
Efficient and timely delivery of vaccine antigens to the secondary lymphoid tissue is crucial to induce protective immune responses by vaccination. However, determining the longitudinal biodistribution of injected vaccines in the body has been a challenge. Here, the near-infrared (NIR) fluorescence imaging is reported that can efficiently enable the trafficking and biodistribution of vaccines in real time. Zwitterionic NIR fluorophores are conjugated on the surface of model vaccines and tracked the fate of bioconjugated vaccines after intradermal administration. Using an NIR fluorescence imaging system, it is possible to obtain time-course imaging of vaccine trafficking through the lymphatics, observing notable uptake in lymph nodes with minimal nonspecific tissue interactions. Flow cytometry analysis confirmed that the uptake in lymph nodes by antigen presenting cells was highly dependent on the hydrodynamic diameter of vaccines. These results demonstrate that the combination of a real-time NIR fluorescence imaging system and zwitterionic fluorophores is a powerful tool to determine the fate of vaccine antigens. Since such non-specific vaccine uptake causes serious adverse reactions, this method is not only useful for optimization of vaccine design, but also for safety evaluation of clinical vaccine candidates.
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Affiliation(s)
- Wataru Katagiri
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital 149 13th Street Charlestown MA 02129 USA
- Graduate School of Science and Technology Keio University 3‐14‐1 Hiyoshi Yokohama Kanagawa 223–8522 Japan
| | - Jeong Heong Lee
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital 149 13th Street Charlestown MA 02129 USA
| | - Marc‐André Tétrault
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital 149 13th Street Charlestown MA 02129 USA
| | - Homan Kang
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital 149 13th Street Charlestown MA 02129 USA
| | - Sinyoung Jeong
- Wellman Center for Photomedicine Department of Dermatology Massachusetts General Hospital 149 13th Street Charlestown MA 02129 USA
| | - Conor L. Evans
- Wellman Center for Photomedicine Department of Dermatology Massachusetts General Hospital 149 13th Street Charlestown MA 02129 USA
| | - Shinya Yokomizo
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital 149 13th Street Charlestown MA 02129 USA
- Department of Radiological Sciences Tokyo Metropolitan University 7‐2‐10 Higashi‐Ogu Arakawa Tokyo 116–8551 Japan
| | - Sheena Santos
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital 149 13th Street Charlestown MA 02129 USA
| | - Catherine Jones
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital 149 13th Street Charlestown MA 02129 USA
| | - Shuang Hu
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital 149 13th Street Charlestown MA 02129 USA
| | - Georges El Fakhri
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital 149 13th Street Charlestown MA 02129 USA
| | - Kosuke Tsukada
- Graduate School of Science and Technology Keio University 3‐14‐1 Hiyoshi Yokohama Kanagawa 223–8522 Japan
| | - Hak Soo Choi
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital 149 13th Street Charlestown MA 02129 USA
| | - Satoshi Kashiwagi
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital 149 13th Street Charlestown MA 02129 USA
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13
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Olson MT, Ly QP, Mohs AM. Fluorescence Guidance in Surgical Oncology: Challenges, Opportunities, and Translation. Mol Imaging Biol 2019; 21:200-218. [PMID: 29942988 PMCID: PMC6724738 DOI: 10.1007/s11307-018-1239-2] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Surgical resection continues to function as the primary treatment option for most solid tumors. However, the detection of cancerous tissue remains predominantly subjective and reliant on the expertise of the surgeon. Surgery that is guided by fluorescence imaging has shown clinical relevance as a new approach to detecting the primary tumor, tumor margins, and metastatic lymph nodes. It is a technique to reduce recurrence and increase the possibility of a curative resection. While significant progress has been made in developing this emerging technology as a tool to assist the surgeon, further improvements are still necessary. Refining imaging agents and tumor targeting strategies to be a precise and reliable surgical strategy is essential in order to translate this technology into patient care settings. This review seeks to provide a comprehensive update on the most recent progress of fluorescence-guided surgery and its translation into the clinic. By highlighting the current status and recent developments of fluorescence image-guided surgery in the field of surgical oncology, we aim to offer insight into the challenges and opportunities that require further investigation.
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Affiliation(s)
- Madeline T Olson
- Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA
- Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Quan P Ly
- Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Aaron M Mohs
- Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 5-12315 Scott Research Tower, Omaha, NE, 68198, USA.
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
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14
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Sajedi S, Sabet H, Choi HS. Intraoperative biophotonic imaging systems for image-guided interventions. NANOPHOTONICS 2019; 8:99-116. [PMID: 31187017 PMCID: PMC6559750 DOI: 10.1515/nanoph-2018-0134] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2023]
Abstract
Biophotonic imaging has revolutionized the operation room by providing surgeons intraoperative image-guidance to diagnose tumors more efficiently and to resect tumors with real-time image navigation. Among many medical imaging modalities, near-infrared (NIR) light is ideal for image-guided surgery because it penetrates relatively deeply into living tissue, while nuclear imaging provides quantitative and unlimited depth information. It is therefore ideal to develop an integrated imaging system by combining NIR fluorescence and gamma-positron imaging to provide surgeons with highly sensitive and quantitative detection of diseases, such as cancer, in real-time without changing the look of the surgical field. The focus of this review is to provide recent progress in intraoperative biophotonic imaging systems, NIR fluorescence imaging and intraoperative nuclear imaging devices, and their future perspectives for image-guided interventions.
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Affiliation(s)
- Salar Sajedi
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Hamid Sabet
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Hak Soo Choi
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
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15
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Wada H, Hyun H, Bao K, Lee JH, El Fakhri G, Choi Y, Choi HS. Multivalent Mannose-Decorated NIR Nanoprobes for Targeting Pan Lymph Nodes. CHEMICAL ENGINEERING JOURNAL (LAUSANNE, SWITZERLAND : 1996) 2018; 340:51-57. [PMID: 29962899 PMCID: PMC6022841 DOI: 10.1016/j.cej.2018.01.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/19/2023]
Abstract
Lymphadenectomy is a prerequisite for most malignancies to define the precise staging of cancer, as well as resect the possible metastases completely. While it improves prognosis, lymphadenectomy often causes postoperative edema or bleeding because of unclear surgical margins. In this study, we synthesized near-infrared (NIR) fluorescent nanoprobes with conjugating various mannose moieties on the surface to target macrophages in the lymph node. Armed with these NIR nanoprobes, we demonstrated the feasibility of intraoperative pan lymph nodes (PLN) mapping and real-time optical imaging under the NIR fluorescence imaging system. We found that even single mannose-conjugated ZW800-1 showed specific uptake in lymph nodes within 4 h, and multiple mannose-employed polyrotaxanes highlighted PLN efficiently with low background signals in major organs. This technology can help surgeons perform lymphadenectomy with ease and safety by identifying all regional lymph nodes proficiently after a single intravenous injection of NIR nanoprobes.
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Affiliation(s)
- Hideyuki Wada
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Hoon Hyun
- Department of Biomedical Science, Chonnam National University Medical School, Gwangju 501-746, South Korea
| | - Kai Bao
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Jeong Heon Lee
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Georges El Fakhri
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Yongdoo Choi
- Biomarker Branch, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi 10408, South Korea
- Corresponding Author: Y.C. ( or H.S.C. ()
| | - Hak Soo Choi
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Corresponding Author: Y.C. ( or H.S.C. ()
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16
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Moore LS, Rosenthal EL, de Boer E, Prince AC, Patel N, Richman JM, Morlandt AB, Carroll WR, Zinn KR, Warram JM. Effects of an Unlabeled Loading Dose on Tumor-Specific Uptake of a Fluorescently Labeled Antibody for Optical Surgical Navigation. Mol Imaging Biol 2018; 19:610-616. [PMID: 27830425 DOI: 10.1007/s11307-016-1022-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE Intraoperative optical imaging to guide surgeons during oncologic resections offers a unique and promising solution to the ambiguity of cancer margins to tactile and visual assessment that results in devastatingly high rates of positive margins. Sequestering of labeled antibodies by normal tissues with high expression of the antibody target, or "antigen sinks", diminishes the efficacy of these probes to provide contrast between the tumor and background tissues by decreasing the amount of circulating probe available for uptake by the tumor and by increasing the fluorescence of non-tumor tissues. We hypothesized that administering a dose of unlabeled antibody prior to infusion of the near-infrared (NIR) fluorescently labeled antibody would improve tumor-specific uptake and contrast of the fluorescently labeled probe by occupying extra-tumoral binding sites, thereby increasing the amount of labeled probe available for uptake by the tumor. PROCEDURES In this study, we explore this concept by testing two different "pre-load" doses of unlabeled cetuximab (the standard 10-mg test dose, and a larger, experimental 100-mg test dose) in six patients receiving cetuximab conjugated to the fluorescent dye IRDye800CW (cetuximab-IRDye800CW) in a clinical trial, and compared the amount of fluorescent antibody in tumor and background tissues, as well as the tumor-specific contrast of each. RESULTS The patients receiving the larger preload (100 mg) of unlabeled cetuximab demonstrated significantly higher concentrations (9.5 vs. 0.1 μg) and a longer half-life (30.3 vs. 20.6 days) of the labeled cetuximab in plasma, as well as significantly greater tumor fluorescence (32.3 vs. 9.3 relative fluorescence units) and tumor to background ratios (TBRs) (5.5 vs. 1.7). CONCLUSIONS Administering a preload of unlabeled antibody prior to infusion of the fluorescently labeled drug may be a simple and effective way to improve the performance of antibody-based probes to guide surgical resection of solid malignancies.
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Affiliation(s)
- Lindsay S Moore
- Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Eben L Rosenthal
- Department of Otolaryngology, Stanford University, Stanford, CA, USA
| | - Esther de Boer
- Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA.,Department of Surgery, University of Groningen, Groningen, the Netherlands
| | - Andrew C Prince
- Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Neel Patel
- Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Joshua M Richman
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Anthony B Morlandt
- Department of Oral & Maxillofacial Surgery, University of Alabama Birmingham, Birmingham, AL, USA
| | - William R Carroll
- Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Kurt R Zinn
- Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jason M Warram
- Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA. .,Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA. .,Departments of Otolaryngology, Neurosurgery, and Radiology, The University of Alabama at Birmingham, 1670 University Blvd., Birmingham, AL, 35294, USA.
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17
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Tummers WS, Miller SE, Teraphongphom NT, Gomez A, Steinberg I, Huland DM, Hong S, Kothapalli SR, Hasan A, Ertsey R, Bonsing BA, Vahrmeijer AL, Swijnenburg RJ, Longacre TA, Fisher GA, Gambhir SS, Poultsides GA, Rosenthal EL. Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging. Ann Surg Oncol 2018; 25:1880-1888. [PMID: 29667116 DOI: 10.1245/s10434-018-6453-2] [Citation(s) in RCA: 121] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND Operative management of pancreatic ductal adenocarcinoma (PDAC) is complicated by several key decisions during the procedure. Identification of metastatic disease at the outset and, when none is found, complete (R0) resection of primary tumor are key to optimizing clinical outcomes. The use of tumor-targeted molecular imaging, based on photoacoustic and fluorescence optical imaging, can provide crucial information to the surgeon. The first-in-human use of multimodality molecular imaging for intraoperative detection of pancreatic cancer is reported using cetuximab-IRDye800, a near-infrared fluorescent agent that binds to epidermal growth factor receptor. METHODS A dose-escalation study was performed to assess safety and feasibility of targeting and identifying PDAC in a tumor-specific manner using cetuximab-IRDye800 in patients undergoing surgical resection for pancreatic cancer. Patients received a loading dose of 100 mg of unlabeled cetuximab before infusion of cetuximab-IRDye800 (50 mg or 100 mg). Multi-instrument fluorescence imaging was performed throughout the surgery in addition to fluorescence and photoacoustic imaging ex vivo. RESULTS Seven patients with resectable pancreatic masses suspected to be PDAC were enrolled in this study. Fluorescence imaging successfully identified tumor with a significantly higher mean fluorescence intensity in the tumor (0.09 ± 0.06) versus surrounding normal pancreatic tissue (0.02 ± 0.01), and pancreatitis (0.04 ± 0.01; p < 0.001), with a sensitivity of 96.1% and specificity of 67.0%. The mean photoacoustic signal in the tumor site was 3.7-fold higher than surrounding tissue. CONCLUSIONS The safety and feasibilty of intraoperative, tumor-specific detection of PDAC using cetuximab-IRDye800 with multimodal molecular imaging of the primary tumor and metastases was demonstrated.
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Affiliation(s)
- Willemieke S Tummers
- Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA, USA.,Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Sarah E Miller
- Department of Otolaryngology, Stanford University, Stanford, CA, USA
| | | | - Adam Gomez
- Department of Pathology, Stanford University, Stanford, CA, USA
| | - Idan Steinberg
- Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA, USA
| | - David M Huland
- Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA, USA
| | - Steve Hong
- Department of Otolaryngology, Stanford University, Stanford, CA, USA
| | - Sri-Rajasekhar Kothapalli
- Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA, USA
| | - Alifia Hasan
- Department of Otolaryngology, Stanford University, Stanford, CA, USA
| | - Robert Ertsey
- Department of Otolaryngology, Stanford University, Stanford, CA, USA
| | - Bert A Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | | | | | - Teri A Longacre
- Department of Pathology, Stanford University, Stanford, CA, USA
| | - George A Fisher
- Department of Medical Oncology, Stanford University, Stanford, CA, USA
| | - Sanjiv S Gambhir
- Departments of Radiology, Bioengineering, and Materials Science & Engineering, Molecular Imaging Program at Stanford; Canary Center at Stanford for Early Cancer Detection, Stanford University, Stanford, CA, USA
| | | | - Eben L Rosenthal
- Department of Otolaryngology, Stanford University, Stanford, CA, USA. .,Stanford Cancer Center, Stanford University, Stanford, CA, USA.
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18
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Li M, Liu C, Gong X, Zheng R, Bai Y, Xing M, Du X, Liu X, Zeng J, Lin R, Zhou H, Wang S, Lu G, Zhu W, Fang C, Song L. Linear array-based real-time photoacoustic imaging system with a compact coaxial excitation handheld probe for noninvasive sentinel lymph node mapping. BIOMEDICAL OPTICS EXPRESS 2018; 9:1408-1422. [PMID: 29675292 PMCID: PMC5905896 DOI: 10.1364/boe.9.001408] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Revised: 12/21/2017] [Accepted: 01/08/2018] [Indexed: 05/04/2023]
Abstract
We developed a linear ultrasound array-based real-time photoacoustic imaging system with a compact coaxial excitation handheld photoacoustic imaging probe for guiding sentinel lymph node (SLN) needle biopsy. Compared with previous studies, our system and probe have the following advantages: (1) the imaging probe is quite compact and user-friendly; (2) laser illumination and ultrasonic detection are achieved coaxially, enabling high signal-to-noise ratio; and (3) GPU-based image reconstruction enables real-time imaging and displaying at a frame rate of 20 Hz. With the system and probe, clear visualization of the SLN at the depth of 2 cm (~human SLN depth) was demonstrated on a living rat. A fine needle was pushed towards the SLN based on the guidance of real-time photoacoustic imaging. The proposed photoacoustic imaging system and probe was shown to have great potential to be used in clinics for guiding SLN needle biopsy, which may reduce the high morbidity rate related to the current gold standard clinical SLN biopsy procedure.
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Affiliation(s)
- Mucong Li
- Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Equal Contribution
| | - Chengbo Liu
- Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Beijing Center for Mathematics and Information Interdisciplinary Sciences (BCMIIS), Beijing 100048, China
- Equal Contribution
| | - Xiaojing Gong
- Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Rongqin Zheng
- Department of Medical Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Yuanyuan Bai
- Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Muyue Xing
- Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Xuemin Du
- Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Xiaoyang Liu
- Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Jing Zeng
- Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Riqiang Lin
- Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Huichao Zhou
- Department of Medical Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Shouju Wang
- Department of Medical Imaging, Jinling Hospital, Nanjing University, Nanjing 210002, China
| | - Guangming Lu
- Department of Medical Imaging, Jinling Hospital, Nanjing University, Nanjing 210002, China
| | - Wen Zhu
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Chihua Fang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Liang Song
- Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- Beijing Center for Mathematics and Information Interdisciplinary Sciences (BCMIIS), Beijing 100048, China
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19
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Weixler B, Rickenbacher A, Raptis DA, Viehl CT, Guller U, Rueff J, Zettl A, Zuber M. Sentinel Lymph Node Mapping with Isosulfan Blue or Indocyanine Green in Colon Cancer Shows Comparable Results and Identifies Patients with Decreased Survival: A Prospective Single-Center Trial. World J Surg 2018; 41:2378-2386. [PMID: 28508233 DOI: 10.1007/s00268-017-4051-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Sentinel lymph node (SLN) mapping was reported to improve lymph node staging in colon cancer. This study compares isosulfan blue (IB) with indocyanine green (ICG)-based SLN-mapping and assesses the prognostic value of isolated tumor cells (ITC) and micro-metastases in upstaged patients. METHODS A total of 220 stage I-III colon cancer patients were included in this prospective single-center study. In 170 patients, SLN-mapping was performed in vivo with IB and in 50 patients ex vivo with ICG. Three levels of each SLN were stained with H&E. If negative for tumor infiltration, immunostaining for cytokeratin (AE1/3; cytokeratin-19) was performed. RESULTS SLN detection rate for IB and ICG was 100 and 98%, respectively. Accuracy and sensitivity was 88 and 75% for IB, 82 and 64% for ICG, respectively (p = 0.244). Overall, 149 (68%) patients were node negative. In these patients, ITC and micro-metastases were detected in 26% (31/129) with IB and 17% (5/29) with ICG (p = 0.469). Patients with ITC and micro-metastases did show decreased overall survival (hazard ratio = 1.96, p = 0.09) compared to node negative disease. CONCLUSIONS This study demonstrates a high diagnostic accuracy for both the IB and the ICG SLN-mapping. SLN-mapping upstaged a quarter of patients with node negative colon cancer, and the detected ITC and micro-metastases were an independent negative prognostic marker in multivariate analysis.
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Affiliation(s)
- Benjamin Weixler
- Department of Surgery, University Hospital Basel, Basel, Switzerland.,Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland
| | - Andreas Rickenbacher
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland.,Department of Visceral Surgery, University Hospital Zürich, Zurich, Switzerland
| | - Dimitri Aristotle Raptis
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland.,Department of Visceral Surgery, University Hospital Zürich, Zurich, Switzerland
| | - Carsten T Viehl
- Department of Surgery, Hospital Center Biel, Biel/Bienne, Switzerland
| | - Ulrich Guller
- Division of Oncology/Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.,University Clinic for Visceral Surgery and Medicine, Inselspital Berne, University of Berne, Berne, Switzerland
| | - Jessica Rueff
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland
| | - Andreas Zettl
- Viollier AG, Histopathology/Cytology, Basel, Switzerland
| | - Markus Zuber
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland.
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20
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Jo D, Hyun H. Structure-Inherent Targeting of Near-Infrared Fluorophores for Image-Guided Surgery. Chonnam Med J 2017; 53:95-102. [PMID: 28584787 PMCID: PMC5457957 DOI: 10.4068/cmj.2017.53.2.95] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Revised: 01/06/2017] [Accepted: 01/10/2017] [Indexed: 12/27/2022] Open
Abstract
Although various clinical imaging modalities have been developed to visualize internal body structures and detect abnormal tissues prior to surgical procedures, most medical imaging modalities do not provide disease-specific images in real-time. Optical imaging can provide the surgeon with real-time visualization of the surgical field for intraoperative image-guided surgery. Imaging in the near-infrared (NIR) window (650-900 nm), also known as the "therapeutic window" has high potential by offering low absorbance and scattering in tissues resulting in minimized background autofluorescence. Clinically, optical fluorescence imaging with the targeted contrast agents provides opportunities for significant advances in intraoperative image-guided surgery. There are only two clinically available NIR fluorophores, indocyanine green (ICG) and methylene blue (MB), that support the image-guided surgery. However, neither of them perform in vivo by providing optimum specificity and stability for targeted image guidance. Therefore, it is of paramount importance to develop targeted NIR fluorophores for unmet clinical needs. Using the right combination of an NIR fluorescence imaging system and a targeted fluorophore, the desired target tissues can be imaged to provide real-time fluorescence guidance without changing the field-of-view during surgery. Thus, in a clinical discipline, the development of NIR fluorophores for 'structure-inherent targeting' is an unmet need for early phase diagnostics with accurate targeting.
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Affiliation(s)
- Danbi Jo
- Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Korea
| | - Hoon Hyun
- Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Korea
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21
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BF 2-azadipyrromethene NIR-emissive fluorophores with research and clinical potential. Eur J Med Chem 2017; 135:392-400. [PMID: 28460313 DOI: 10.1016/j.ejmech.2017.04.051] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Revised: 04/14/2017] [Accepted: 04/20/2017] [Indexed: 12/26/2022]
Abstract
The use of near-infrared fluorescence for in vivo research and intraoperative clinical imaging is rapidly expanding, with new applications being proposed and developed. While imaging hardware and software have significantly progressed in recent times, the molecular fluorescent agents remain a limiting factor. In this report, the design, synthesis, photophysical characterization and bio-medical imaging assessment of two new NIR-fluorophores based on the BF2-azadipyrromethene fluorophore class are described. Inclusion of dimethylamino substituents on these BF2-azadipyrromethene probes results in very large bathochromic shifts with photophysical measurements showing absorption and emission maxima between 757 and 818 nm within the desired NIR spectra region. Testing of the probes shows that they are suitable for fluorescence imaging with both research and clinical instrumentation. Preclinical imaging assessment shows their suitability as fluorescent markers (tattoos) of lesions for intraoperative identification and lymphatic mapping in ex vivo human colonic tissue. These new clinical wavelength-compatible fluorophores may contribute towards the on-going expansion of medical uses for NIR-fluorescence.
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He J, Yang L, Yi W, Fan W, Wen Y, Miao X, Xiong L. Combination of Fluorescence-Guided Surgery With Photodynamic Therapy for the Treatment of Cancer. Mol Imaging 2017; 16:1536012117722911. [PMID: 28849712 PMCID: PMC5580848 DOI: 10.1177/1536012117722911] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Revised: 03/07/2017] [Accepted: 06/28/2017] [Indexed: 12/12/2022] Open
Abstract
Specific visualization of body parts is needed during surgery. Fluorescence-guided surgery (FGS) uses a fluorescence contrast agent for in vivo tumor imaging to detect and identify both malignant and normal tissues. There are several advantages and clinical benefits of FGS over other conventional medical imaging modalities, such as its safety, effectiveness, and suitability for real-time imaging in the operating room. Recent advancements in contrast agents and intraoperative fluorescence imaging devices have led to a greater potential for intraoperative fluorescence imaging in clinical applications. Photodynamic therapy (PDT) is an alternative modality to treat tumors, which uses a light-sensitive drug (photosensitizers) and special light to destroy the targeted tissues. In this review, we discuss the fluorescent contrast agents, some newly developed imaging devices, and the successful clinical application of FGS. Additionally, we present the combined strategy of FGS with PDT to further improve the therapeutic effect for patients with cancer. Taken together, this review provides a unique perspective and summarization of FGS.
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Affiliation(s)
- Jun He
- General Surgery Department, Second Xiangya Hospital, Central South University, Changsha, China
| | - Leping Yang
- General Surgery Department, Second Xiangya Hospital, Central South University, Changsha, China
| | - Wenjun Yi
- General Surgery Department, Second Xiangya Hospital, Central South University, Changsha, China
| | - Wentao Fan
- General Surgery Department, Second Xiangya Hospital, Central South University, Changsha, China
| | - Yu Wen
- General Surgery Department, Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiongying Miao
- General Surgery Department, Second Xiangya Hospital, Central South University, Changsha, China
| | - Li Xiong
- General Surgery Department, Second Xiangya Hospital, Central South University, Changsha, China
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Pouw JJ, Grootendorst MR, Klaase JM, van Baarlen J, Ten Haken B. Ex vivo sentinel lymph node mapping in colorectal cancer using a magnetic nanoparticle tracer to improve staging accuracy: a pilot study. Colorectal Dis 2016; 18:1147-1153. [PMID: 27218666 DOI: 10.1111/codi.13395] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Revised: 02/24/2016] [Accepted: 02/29/2016] [Indexed: 02/08/2023]
Abstract
AIM Nodal status is the most important prognostic factor in colorectal cancer (CRC). Small occult metastases may remain undetected on conventional histopathological examination, potentially resulting in undertreatment. Ex vivo sentinel lymph node mapping (SLNM) can be used to improve the accuracy of nodal staging, but the currently used tracers suffer from drawbacks, which hamper implementation of the technique in routine clinical practice. Magnetic tracers are the optimal size for sentinel lymph node (SLN) retention and allow objective quantitative selection of SLNs; they therefore have great potential for SLNM in CRC. The study evaluates the feasibility of ex vivo magnetic SLNM and compares the performance of this technique with blue dye SLNM. METHOD Twenty-eight ex vivo SLNM procedures were performed in 27 histological node-negative patients with CRC using a magnetic tracer and blue dye. A magnetometer was used to select magnetic SLNs after formalin fixation of the CRC specimen. Both magnetic and blue SLNs were subjected to serial sectioning and immunohistochemical staining to reveal occult metastases. RESULTS At least one SLN was successfully identified in 27/28 (96%) and 25/28 (89%) of the cases with the magnetic technique and blue dye. Isolated tumour cells were detected in 10 patients. This was predicted with 100% sensitivity and accuracy using the magnetic technique, and with 91% sensitivity and 96% accuracy using the blue dye technique. CONCLUSION This study demonstrates that ex vivo magnetic SLNM is a feasible technique for use in routine clinical practice, improving nodal staging accuracy of CRC patients.
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Affiliation(s)
- J J Pouw
- MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands
| | - M R Grootendorst
- MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.,Department of Surgery, Medisch Spectrum Twente, Enschede, The Netherlands
| | - J M Klaase
- Department of Surgery, Medisch Spectrum Twente, Enschede, The Netherlands
| | - J van Baarlen
- Laboratorium Pathologie Oost Nederland, Hengelo, The Netherlands
| | - B Ten Haken
- MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands
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Opacic T, Paefgen V, Lammers T, Kiessling F. Status and trends in the development of clinical diagnostic agents. WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY 2016; 9. [DOI: 10.1002/wnan.1441] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 09/02/2016] [Accepted: 09/15/2016] [Indexed: 12/12/2022]
Affiliation(s)
- Tatjana Opacic
- Department of Experimental Molecular Imaging; RWTH Aachen University; Aachen Germany
| | - Vera Paefgen
- Department of Experimental Molecular Imaging; RWTH Aachen University; Aachen Germany
| | - Twan Lammers
- Department of Experimental Molecular Imaging; RWTH Aachen University; Aachen Germany
- Department of Pharmaceutics; Utrecht University; Utrecht The Netherlands
- Department of Targeted Therapeutics; University of Twente; Enschede The Netherlands
| | - Fabian Kiessling
- Department of Experimental Molecular Imaging; RWTH Aachen University; Aachen Germany
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Porcu EP, Salis A, Gavini E, Rassu G, Maestri M, Giunchedi P. Indocyanine green delivery systems for tumour detection and treatments. Biotechnol Adv 2016; 34:768-789. [PMID: 27090752 DOI: 10.1016/j.biotechadv.2016.04.001] [Citation(s) in RCA: 118] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Revised: 03/31/2016] [Accepted: 04/01/2016] [Indexed: 01/16/2023]
Abstract
Indocyanine green (ICG) is a cyanine compound that displays fluorescent properties in the near infrared region. This dye is employed for numerous indications but nowadays its major application field regards tumour diagnosis and treatments. Optical imaging by near infrared fluorescence provides news opportunities for oncologic surgery. The imaging of ICG can be useful for intraoperative identification of several solid tumours and metastases, and sentinel lymph node detection. In addition, ICG can be used as an agent for the destruction of malignant tissue, by virtue of the production of reactive oxygen species and/or induction of a hyperthermia effect under irradiation. Nevertheless, ICG shows several drawbacks, which limit its clinical application. Several formulative strategies have been studied to overcome these problems. The rationale of the development of ICG containing drug delivery systems is to enhance the in vivo stability and biodistribution profile of this dye, allowing tumour accumulation and resulting in better efficacy. In this review, ICG containing nano-sized carriers are classified based on their chemical composition and structure. In addition to nanosystems, different formulations including hydrogel, microsystems and others loaded with ICG will be illustrated. In particular, this report describes the preparation, in vitro characterization and in vivo application of ICG platforms for cancer imaging and treatment. The promising results of all systems confirm their clinical utility but further studies are required prior to evaluating the formulations in human trials.
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Affiliation(s)
- Elena P Porcu
- PhD in Experimental Medicine, Department of Diagnostic, Paediatric, Clinical and Surgical Science, Pavia, Italy
| | - Andrea Salis
- University of Sassari, Department of Chemistry and Pharmacy, Sassari, Italy
| | - Elisabetta Gavini
- University of Sassari, Department of Chemistry and Pharmacy, Sassari, Italy
| | - Giovanna Rassu
- University of Sassari, Department of Chemistry and Pharmacy, Sassari, Italy
| | | | - Paolo Giunchedi
- University of Sassari, Department of Chemistry and Pharmacy, Sassari, Italy.
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Bao K, Nasr KA, Hyun H, Lee JH, Gravier J, Gibbs SL, Choi HS. Charge and hydrophobicity effects of NIR fluorophores on bone-specific imaging. Theranostics 2015; 5:609-17. [PMID: 25825600 PMCID: PMC4377729 DOI: 10.7150/thno.11222] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Accepted: 01/23/2015] [Indexed: 12/04/2022] Open
Abstract
Recent advances in near-infrared (NIR) fluorescence imaging enabled real-time intraoperative detection of bone metastases, bone growth, and tissue microcalcification. Pamidronate (PAM) has been widely used for this purpose because of its high binding affinity toward bone and remarkable therapeutic effects. Herein we describe the development of a series of PAM-conjugated NIR fluorophores that varied in net charges and hydrophobicity, and compared their bone targeting efficiency, biodistribution, and blood clearance. Since the targeting moiety, PAM, is highly negatively charged but small, the overall in vivo bone targeting and biodistribution were mediated by the physicochemical properties of conjugated fluorophores.
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Chi C, Du Y, Ye J, Kou D, Qiu J, Wang J, Tian J, Chen X. Intraoperative imaging-guided cancer surgery: from current fluorescence molecular imaging methods to future multi-modality imaging technology. Theranostics 2014; 4:1072-84. [PMID: 25250092 PMCID: PMC4165775 DOI: 10.7150/thno.9899] [Citation(s) in RCA: 275] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Accepted: 07/31/2014] [Indexed: 12/20/2022] Open
Abstract
Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications. Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery.
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Ashitate Y, Hyun H, Kim SH, Lee JH, Henary M, Frangioni JV, Choi HS. Simultaneous mapping of pan and sentinel lymph nodes for real-time image-guided surgery. Am J Cancer Res 2014; 4:693-700. [PMID: 24883119 PMCID: PMC4038751 DOI: 10.7150/thno.8721] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Accepted: 03/24/2014] [Indexed: 12/27/2022] Open
Abstract
The resection of regional lymph nodes in the basin of a primary tumor is of paramount importance in surgical oncology. Although sentinel lymph node mapping is now the standard of care in breast cancer and melanoma, over 20% of patients require a completion lymphadenectomy. Yet, there is currently no technology available that can image all lymph nodes in the body in real time, or assess both the sentinel node and all nodes simultaneously. In this study, we report an optical fluorescence technology that is capable of simultaneous mapping of pan lymph nodes (PLNs) and sentinel lymph nodes (SLNs) in the same subject. We developed near-infrared fluorophores, which have fluorescence emission maxima either at 700 nm or at 800 nm. One was injected intravenously for identification of all regional lymph nodes in a basin, and the other was injected locally for identification of the SLN. Using the dual-channel FLARE intraoperative imaging system, we could identify and resect all PLNs and SLNs simultaneously. The technology we describe enables simultaneous, real-time visualization of both PLNs and SLNs in the same subject.
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29
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Lymphatic spread, nodal count and the extent of lymphadenectomy in cancer of the colon. Cancer Treat Rev 2014; 40:405-13. [DOI: 10.1016/j.ctrv.2013.09.013] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2013] [Revised: 09/13/2013] [Accepted: 09/16/2013] [Indexed: 02/08/2023]
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Abstract
Medical imaging plays a critical role in cancer diagnosis and planning. Many of these patients rely on surgical intervention for curative outcomes. This requires a careful identification of the primary and microscopic tumors, and the complete removal of cancer. Although there have been efforts to adapt traditional-imaging modalities for intraoperative image guidance, they suffer from several constraints such as large hardware footprint, high-operation cost, and disruption of the surgical workflow. Because of the ease of image acquisition, relatively low-cost devices and intuitive operation, optical imaging methods have received tremendous interests for use in real-time image-guided surgery. To improve imaging depth under low interference by tissue autofluorescence, many of these applications utilize light in the near-infrared (NIR) wavelengths, which is invisible to human eyes. With the availability of a wide selection of tumor-avid contrast agents, advancements in imaging sensors, electronic and optical designs, surgeons are able to combine different attributes of NIR optical imaging techniques to improve treatment outcomes. The emergence of diverse commercial and experimental image guidance systems, which are in various stages of clinical translation, attests to the potential high impact of intraoperative optical imaging methods to improve speed of oncologic surgery with high accuracy and minimal margin positivity.
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Affiliation(s)
- Suman B Mondal
- Department of Radiology, Washington University in St. Louis, St. Louis, Missouri, USA; Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA
| | - Shengkui Gao
- Department of Computer Science and Engineering, Washington University in St. Louis, St. Louis, Missouri, USA
| | - Nan Zhu
- College of Optical Sciences, University of Arizona, Tucson, Arizona, USA
| | - Rongguang Liang
- College of Optical Sciences, University of Arizona, Tucson, Arizona, USA
| | - Viktor Gruev
- Department of Computer Science and Engineering, Washington University in St. Louis, St. Louis, Missouri, USA
| | - Samuel Achilefu
- Department of Radiology, Washington University in St. Louis, St. Louis, Missouri, USA.
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Oh Y, Lee YS, Quan YH, Choi Y, Jeong JM, Kim BM, Kim HK. Thoracoscopic color and fluorescence imaging system for sentinel lymph node mapping in porcine lung using indocyanine green-neomannosyl human serum albumin: intraoperative image-guided sentinel nodes navigation. Ann Surg Oncol 2013; 21:1182-8. [PMID: 24310791 DOI: 10.1245/s10434-013-3381-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2013] [Indexed: 01/05/2023]
Abstract
PURPOSE This study was performed to validate a newly developed sentinel lymph node (SLN) targeting tracer, indocyanine green-neomannosyl human serum albumin (ICG:MSA), and a thoracoscopic version of the intraoperative color and fluorescence imaging system (ICFIS) for lung cancer SLN mapping. METHODS ICG alone or ICG:MSA (5 μg/kg) was injected into the rat thigh, and the results were compared. The fluorescence signal-to-background ratios of SLNs were recorded and evaluated over a 2-h period by using ICFIS. Additionally, a SLN biopsy was performed via video-assisted thoracoscopic surgery with the use of ICG:MSA in porcine lung by using thoracoscopic ICFIS. RESULTS The newly developed ICG:MSA showed a significantly improved signal-to-background ratio compared with ICG alone throughout the trials. All SLNs were identified in both rats (ten SLNs in ten rat thighs) and pigs (ten SLNs in ten porcine lungs) under in vivo conditions. All SLNs were dissected successfully by using video-assisted thoracoscopic surgery with the help of thoracoscopic ICFIS. DISCUSSION ICG:MSA accumulates in the SLN by uptake and retention through the mannose-specific receptors on macrophages. Thoracoscopic ICFIS successfully assisted SLN mapping despite low near-infrared light transmission in the commercial thoracoscope. On the basis of the results of the thoracoscopic SLN mapping, we anticipate that ICG:MSA and thoracoscopic ICFIS can be translated to clinical trials in the near future.
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Affiliation(s)
- Yujin Oh
- Department of Bio-Convergence, Korea University, Seoul, Korea
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van der Vorst JR, Schaafsma BE, Verbeek FPR, Swijnenburg RJ, Tummers QRJG, Hutteman M, Hamming JF, Kievit J, Frangioni JV, van de Velde CJH, Vahrmeijer AL. Intraoperative near-infrared fluorescence imaging of parathyroid adenomas with use of low-dose methylene blue. Head Neck 2013; 36:853-8. [PMID: 23720199 DOI: 10.1002/hed.23384] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2012] [Revised: 03/05/2013] [Accepted: 05/15/2013] [Indexed: 11/07/2022] Open
Abstract
BACKGROUND Intraoperative identification of parathyroid adenomas can be challenging. We hypothesized that low-doses methylene blue (MB) and near-infrared fluorescence (NIRF) imaging could be used to identify parathyroid adenomas intraoperatively. METHODS MB was injected intravenously after exploration at a dose of 0.5 mg/kg into 12 patients who underwent parathyroid surgery. NIRF imaging was performed using the Mini-FLARE imaging system. RESULTS In 10 of 12 patients, histology confirmed a parathyroid adenoma. In 9 of these patients, NIRF could clearly identify the parathyroid adenoma during surgery. Seven of these 9 patients had a positive preoperative (99m) Tc-sestamibi single photon emission CT (SPECT) scan. Importantly, in 2 patients, parathyroid adenomas could be identified only using NIRF. CONCLUSION This is the first study to show that low-dose MB can be used as NIRF tracer for identification of parathyroid adenomas, and suggests a correlation with preoperative (99m) Tc-sestamibi SPECT scanning.
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Viehl CT, Guller U, Langer I, Laffer U, Oertli D, Zuber M. Factors influencing the success of in vivo sentinel lymph node procedure in colon cancer patients: Swiss prospective, multicenter study sentinel lymph node procedure in colon cancer. World J Surg 2013; 37:873-7. [PMID: 23354923 DOI: 10.1007/s00268-013-1910-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND The sentinel lymph node (SLN) procedure has the potential to provide relevant improvement in nodal staging in colon cancer patients. However, there remains room for improvement for SLN identification and sensitivity. Therefore, the objective of the present investigation was to analyze factors influencing the success of the SLN procedure in colon cancer patients. METHODS One hundred seventy-four consecutive colon cancer patients were prospectively enrolled in this multicenter study and underwent in vivo SLN procedure with isosulfan blue 1 % followed by open standard oncologic colon resection. Several patient-, tumor-, and procedure-related factors possibly influencing the SLN identification and sensitivity were analyzed. RESULTS Sentinel lymph node identification rate and accuracy were 89.1 and 83.9 %, respectively. Successful identification of SLN was significantly associated with the intraoperative visualization of blue lymphatic vessels (p < 0.001) and with female gender (p = 0.024). True positive SLN results were significantly associated with higher numbers of SLN (p = 0.026) and with pN2 stage (p = 0.004). There was a trend toward better sensitivity in patients with lower body mass index (BMI) (p = 0.050). CONCLUSIONS The success of the SLN procedure in colon cancer patients depends on both procedure-related factors (intraoperative visualization of blue lymphatic vessels, high number of SLN identified) and patient factors (gender, BMI). While patient factors can not be influenced, intraoperative visualization of blue lymphatics and identification of high numbers of SLN are key for a successful SLN procedure.
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Affiliation(s)
- Carsten T Viehl
- Department of Surgery, University Hospital Basel, 4031, Basel, Switzerland.
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Abstract
Paradigm shifts in surgery arise when surgeons are empowered to perform surgery faster, better and less expensively than current standards. Optical imaging that exploits invisible near-infrared (NIR) fluorescent light (700-900 nm) has the potential to improve cancer surgery outcomes, minimize the time patients are under anaesthesia and lower health-care costs largely by way of its improved contrast and depth of tissue penetration relative to visible light. Accordingly, the past few years have witnessed an explosion of proof-of-concept clinical trials in the field. In this Review, we introduce the concept of NIR fluorescence imaging for cancer surgery, examine the clinical trial literature to date and outline the key issues pertaining to imaging system and contrast agent optimization. Although NIR seems to be superior to many traditional imaging techniques, its incorporation into routine care of patients with cancer depends on rigorous clinical trials and validation studies.
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Arezzo A, Arolfo S, Mistrangelo M, Mussa B, Cassoni P, Morino M. Transrectal sentinel lymph node biopsy for early rectal cancer during transanal endoscopic microsurgery. MINIM INVASIV THER 2013; 23:17-20. [DOI: 10.3109/13645706.2013.789061] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Biffi S, Dal Monego S, Dullin C, Garrovo C, Bosnjak B, Licha K, Welker P, Epstein MM, Alves F. Dendritic polyglycerolsulfate near infrared fluorescent (NIRF) dye conjugate for non-invasively monitoring of inflammation in an allergic asthma mouse model. PLoS One 2013; 8:e57150. [PMID: 23437332 PMCID: PMC3578827 DOI: 10.1371/journal.pone.0057150] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2012] [Accepted: 01/21/2013] [Indexed: 01/20/2023] Open
Abstract
Background Non-invasive in vivo imaging strategies are of high demand for longitudinal monitoring of inflammation during disease progression. In this study we present an imaging approach using near infrared fluorescence (NIRF) imaging in combination with a polyanionic macromolecular conjugate as a dedicated probe, known to target L- and P-selectin and C3/C5 complement factors. Methodology/Principal Findings We investigated the suitability of dendritic polyglycerol sulfates (dPGS), conjugated with a hydrophilic version of the indocyanine green label with 6 sulfonate groups (6S-ICG) to monitor sites of inflammation using an experimental mouse model of allergic asthma. Accumulation of the NIRF-conjugated dPGS (dPGS-NIRF) in the inflamed lungs was analyzed in and ex vivo in comparison with the free NIRF dye using optical imaging. Commercially available smart probes activated by matrix metalloproteinase's (MMP) and cathepsins were used as a comparative control. The fluorescence intensity ratio between lung areas of asthmatic and healthy mice was four times higher for the dPGS in comparison to the free dye in vivo at four hrs post intravenous administration. No significant difference in fluorescence intensity between healthy and asthmatic mice was observed 24 hrs post injection for dPGS-NIRF. At this time point ex-vivo scans of asthmatic mice confirmed that the fluorescence within the lungs was reduced to approximately 30% of the intensity observed at 4 hrs post injection. Conclusions/Significance Compared with smart-probes resulting in a high fluorescence level at 24 hrs post injection optical imaging with dPGS-NIRF conjugates is characterized by fast uptake of the probe at inflammatory sites and represents a novel approach to monitor lung inflammation as demonstrated in mice with allergic asthma.
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Affiliation(s)
- Stefania Biffi
- Cluster in Biomedicine (CBM scrl), Optical Imaging Laboratory, Trieste, Italy.
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Schaafsma BE, Verbeek FPR, van der Vorst JR, Hutteman M, Kuppen PJK, Frangioni JV, van de Velde CJH, Vahrmeijer AL. Ex vivo sentinel node mapping in colon cancer combining blue dye staining and fluorescence imaging. J Surg Res 2013; 183:253-7. [PMID: 23391167 DOI: 10.1016/j.jss.2013.01.003] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2012] [Revised: 12/11/2012] [Accepted: 01/03/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND The sentinel lymph node procedure has been proposed to improve nodal staging in colon cancer patients. The aim of this study was to assess the added value of near-infrared (NIR) fluorescence imaging to conventional blue dye staining for ex vivo sentinel lymph node mapping. MATERIALS AND METHODS We included 22 consecutive patients undergoing surgery for colon cancer. After tumor resection, we submucosally injected a premixed cocktail of the near-infrared lymphatic tracer HSA800 and blue dye around the tumor for detection of sentinel lymph nodes. We used the Mini-FLARE imaging system for fluorescence imaging. RESULTS In 95% of patients, we identified at least one sentinel lymph node. Overall, a total of 77 sentinel lymph nodes were identified, 77 of which were fluorescent (100%) and 70 of which were blue (91%). Sentinel lymph nodes that were located deeper in the mesenteric fat could easily be located by NIR fluorescence. In four of five patients with lymph node metastases, tumor cells were present in at least one of the sentinel lymph nodes. CONCLUSIONS This study shows the successful use and added value of the NIR fluorescence tracer HSA800 to conventional blue dye for the ex vivo sentinel lymph node procedure in colon cancer.
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Lee JH, Park G, Hong GH, Choi J, Choi HS. Design considerations for targeted optical contrast agents. Quant Imaging Med Surg 2013; 2:266-73. [PMID: 23289086 DOI: 10.3978/j.issn.2223-4292.2012.12.04] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Accepted: 12/17/2012] [Indexed: 12/28/2022]
Abstract
Optical fluorescence imaging with the right combination of imaging modality and targeted contrast agents offers tremendous improvement in intraoperative imaging and clinical output (i.e., image-guided cancer surgery). Therefore, it is of paramount importance to gain an in-depth knowledge in the design of targeted contrast agents to meet clinical requirements. Currently, there are several clinically approved contrast agents available; however, none perform optimally in vivo by providing optimum sensitivity, stability, specificity, and safety for target imaging, diagnosis, and therapy. In this review, we discuss basic design considerations for targeted contrast agents in terms of optical and physicochemical properties, biological and physiological interactions, and biodistribution and targeting.
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Affiliation(s)
- Jeong Heon Lee
- Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; ; Center for Molecular Imaging, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
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Chi C, Ye J, Ding H, He D, Huang W, Zhang GJ, Tian J. Use of indocyanine green for detecting the sentinel lymph node in breast cancer patients: from preclinical evaluation to clinical validation. PLoS One 2013; 8:e83927. [PMID: 24358319 PMCID: PMC3865279 DOI: 10.1371/journal.pone.0083927] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Accepted: 11/10/2013] [Indexed: 02/05/2023] Open
Abstract
Assessment of the sentinel lymph node (SLN) in patients with early stage breast cancer is vital in selecting the appropriate surgical approach. However, the existing methods, including methylene blue and nuclides, possess low efficiency and effectiveness in mapping SLNs, and to a certain extent exert side effects during application. Indocyanine green (ICG), as a fluorescent dye, has been proved reliable usage in SLN detection by several other groups. In this paper, we introduce a novel surgical navigation system to detect SLN with ICG. This system contains two charge-coupled devices (CCD) to simultaneously capture real-time color and fluorescent video images through two different bands. During surgery, surgeons only need to follow the fluorescence display. In addition, the system saves data automatically during surgery enabling surgeons to find the registration point easily according to image recognition algorithms. To test our system, 5 mice and 10 rabbits were used for the preclinical setting and 22 breast cancer patients were utilized for the clinical evaluation in our experiments. The detection rate was 100% and an average of 2.7 SLNs was found in 22 patients. Our results show that the usage of our surgical navigation system with ICG to detect SLNs in breast cancer patients is technically feasible.
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Affiliation(s)
- Chongwei Chi
- Intelligent Medical Research Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China
| | - Jinzuo Ye
- Intelligent Medical Research Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China
| | - Haolong Ding
- The Breast Center, Cancer Hospital, Shantou University Medical College, Shantou, China
| | - De He
- The Breast Center, Cancer Hospital, Shantou University Medical College, Shantou, China
| | - Wenhe Huang
- The Breast Center, Cancer Hospital, Shantou University Medical College, Shantou, China
| | - Guo-Jun Zhang
- The Breast Center, Cancer Hospital, Shantou University Medical College, Shantou, China
- * E-mail: (GJZ); (JT)
| | - Jie Tian
- Intelligent Medical Research Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China
- * E-mail: (GJZ); (JT)
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Hirche C, Engel H, Kolios L, Cognie J, Hünerbein M, Lehnhardt M, Kremer T. An experimental study to evaluate the Fluobeam 800 imaging system for fluorescence-guided lymphatic imaging and sentinel node biopsy. Surg Innov 2012; 20:516-23. [PMID: 23275469 DOI: 10.1177/1553350612468962] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Visualization of the lymphatic system is challenging. Lymphatic imaging is a crucial diagnostic tool for benign and malignant lymphatic pathologies. Fluorescence-guided imaging allows selective lymphatic mapping and sentinel lymph node (SLN) identification. There are a few fluorescence systems, but some drawbacks remain due to technical and ergonomic aspects. The aim of this study was to evaluate the feasibility of the new Fluobeam 800 imaging system. METHODS After approval by the ethics committee, the system was evaluated for lymphography and SLN biopsy in an animal model. Five pigs each with 4 lymph node (LN) stations (n = 20 LN stations) were subjected to lymphatic imaging using indocyanine green (ICG). Additionally, the use of ICG was compared with ICG adsorbed to human serum albumin (ICG-HSA). Lymphatic vessels and SLN identification rates were measured. RESULTS After injection, a clear fluorescence signal of the lymphatic vessels was visualized leading to the LN station. Overall, ICG fluorescence imaging identified a mean of 2.0 lymphatic vessels and 1.1 (range = 1-2) SLN in 20 of 20 LN stations. Reverse lymphography was feasible. A clinical difference in resolution was not detected between use of ICG-HSA and ICG. CONCLUSION This is the first study analyzing the feasibility of the Fluobeam 800 imaging system allowing transcutaneous real-time imaging. It enables detection of the SLN by fluorescence retention with increased detection depth and resolution. After fixation to the ceiling, the ergonomics advanced for simultaneous field navigation and dissection. The new system can be applied for lymphatic imaging for lympatico-reconstructive surgery and SLN biopsy.
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42
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Gibbs SL. Near infrared fluorescence for image-guided surgery. Quant Imaging Med Surg 2012; 2:177-87. [PMID: 23256079 DOI: 10.3978/j.issn.2223-4292.2012.09.04] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2012] [Accepted: 09/24/2012] [Indexed: 01/22/2023]
Abstract
Near infrared (NIR) image-guided surgery holds great promise for improved surgical outcomes. A number of NIR image-guided surgical systems are currently in preclinical and clinical development with a few approved for limited clinical use. In order to wield the full power of NIR image-guided surgery, clinically available tissue and disease specific NIR fluorophores with high signal to background ratio are necessary. In the current review, the status of NIR image-guided surgery is discussed along with the desired chemical and biological properties of NIR fluorophores. Lastly, tissue and disease targeting strategies for NIR fluorophores are reviewed.
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Affiliation(s)
- Summer L Gibbs
- Department of Biomedical Engineering, Center for Spatial Systems Biomedicine, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA
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43
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Nonprofit foundations for open-source biomedical technology development. Nat Biotechnol 2012; 30:928-32. [DOI: 10.1038/nbt.2392] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Tiernan JP, Ansari I, Hirst NA, Millner PA, Hughes TA, Jayne DG. Intra-operative tumour detection and staging in colorectal cancer surgery. Colorectal Dis 2012; 14:e510-20. [PMID: 22564278 DOI: 10.1111/j.1463-1318.2012.03078.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
AIM Surgical resection for colorectal cancer involves segmental resection and regional lymphadenectomy. The appropriateness of this 'one-size-fits-all' strategy is questioned as bowel cancer screening programmes result in a shift to earlier stage disease. Currently, the nodal status of a colorectal cancer can only be reliably determined by histopathological examination of the resected specimen. New methods of intra-operative staging are required to allow surgical resection to be tailored to the stage of the disease. METHOD A literature search was performed of PubMed and Embase databases using the terms 'colon' OR 'colorectal' AND 'intra-operative detection' OR 'intra-operative staging' OR 'intra-operative detection' OR 'radioimmunoguided surgery'. Articles published between January 1980 and January 2012 were included. Technologies that have the potential to allow intra-operative staging and treatment stratification were identified and further searches performed. RESULTS Established techniques such as sentinel lymph node mapping and radioimmunoguided surgery have benefited from combination with other technologies to allow real-time intra-operative staging. Intra-operative fluorescence, using naturally fluorescent biomarkers or fluorescent tumour probes, probably offers the most practical means of intra-operative lymph node staging and may be facilitated using nanotechnology. Optical coherence tomography and real-time elastography have the potential to provide an in vivo'virtual biopsy'. CONCLUSION Technological advances may allow accurate intra-operative lymph node staging to facilitate tailored surgical resection. This may become the next paradigm shift in colorectal cancer surgery.
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Affiliation(s)
- J P Tiernan
- Section of Translational Anaesthetic and Surgical Sciences, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK.
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45
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Current world literature. Curr Opin Urol 2012; 22:160-5. [PMID: 22297787 DOI: 10.1097/mou.0b013e328350f678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Zhu B, Tan IC, Rasmussen JC, Sevick-Muraca EM. Validating the Sensitivity and Performance of Near-Infrared Fluorescence Imaging and Tomography Devices Using a Novel Solid Phantom and Measurement Approach. Technol Cancer Res Treat 2012; 11:95-104. [DOI: 10.7785/tcrt.2012.500238] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
With the aid of indocyanine green (ICG), lymphatic architecture and function in both mice and humans has been successfully imaged non-invasively using near-infrared (NIR) fluorescence imaging devices. Maximal measurement sensitivity of NIR fluorescence imaging devices is needed for “first-in-humans” molecularly targeting NIR fluorescence agents that are brighter than non-specific ICG. In this study, we developed a solid phantom and measurement approach for the quantification of excitation light leakage and measurement sensitivity of NIR fluorescence imaging devices. The constructed solid phantom, consisting of quantum dots impregnated onto specularly reflective surface, shows long-term stability and can be used as a traceable fluorescence standard. With the constructed solid phantom, the intensified CCD (ICCD)-based device demonstrated more than 300% higher measurement sensitivity compared to the Electron Multiplying CCD (EMCCD) based device when integration time was maintained less than 1.0 s.
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Affiliation(s)
- B. Zhu
- Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030
| | - I.-C. Tan
- Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030
| | - J. C. Rasmussen
- Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030
| | - E. M. Sevick-Muraca
- Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030
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Schaafsma BE, Mieog JD, Hutteman M, van der Vorst JR, Kuppen PJ, Löwik CW, Frangioni JV, van de Velde CJ, Vahrmeijer AL. The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery. J Surg Oncol 2011; 104:323-32. [PMID: 21495033 PMCID: PMC3144993 DOI: 10.1002/jso.21943] [Citation(s) in RCA: 611] [Impact Index Per Article: 43.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2011] [Accepted: 03/19/2011] [Indexed: 12/21/2022]
Abstract
Optical imaging using near-infrared (NIR) fluorescence provides new prospects for general and oncologic surgery. ICG is currently utilised in NIR fluorescence cancer-related surgery for three indications: sentinel lymph node (SLN) mapping, intraoperative identification of solid tumours, and angiography during reconstructive surgery. Therefore, understanding its advantages and limitations is of significant importance. Although non-targeted and non-conjugatable, ICG appears to be laying the foundation for more widespread use of NIR fluorescence-guided surgery.
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Affiliation(s)
| | - J.Sven D. Mieog
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Merlijn Hutteman
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | | | - Peter J.K. Kuppen
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Clemens W.G.M. Löwik
- Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
| | - John V. Frangioni
- Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA
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Hutteman M, Mieog JSD, van der Vorst JR, Liefers GJ, Putter H, Löwik CW, Frangioni JV, van de Velde CJ, Vahrmeijer AL. Randomized, double-blind comparison of indocyanine green with or without albumin premixing for near-infrared fluorescence imaging of sentinel lymph nodes in breast cancer patients. Breast Cancer Res Treat 2011; 127:163-70. [PMID: 21360075 PMCID: PMC3667709 DOI: 10.1007/s10549-011-1419-0] [Citation(s) in RCA: 119] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2011] [Accepted: 02/18/2011] [Indexed: 10/18/2022]
Abstract
Near-infrared (NIR) fluorescence imaging has the potential to improve sentinel lymph node (SLN) mapping in breast cancer. Indocyanine green (ICG) is currently the only clinically available fluorophore that can be used for SLN mapping. Preclinically, ICG adsorbed to human serum albumin (ICG:HSA) improves its performance as a lymphatic tracer in some anatomical sites. The benefit of ICG:HSA for SLN mapping of breast cancer has not yet been assessed in a clinical trial. We performed a double-blind, randomized study to determine if ICG:HSA has advantages over ICG alone. The primary endpoint was the fluorescence brightness, defined as the signal-to-background ratio (SBR), of identified SLNs. Clinical trial subjects were 18 consecutive breast cancer patients scheduled to undergo SLN biopsy. All patients received standard of care using (99m)Technetium-nanocolloid and patent blue. Patients were randomly assigned to receive 1.6 ml of 500 μM ICG:HSA or ICG that was injected periareolarly directly after patent blue. The Mini-Fluorescence-Assisted Resection and Exploration (Mini-FLARE) imaging system was used for NIR fluorescence detection and quantitation. SLN mapping was successful in all patients. Patient, tumor, and treatment characteristics were equally distributed over the treatment groups. No significant difference was found in SBR between the ICG:HSA group and the ICG alone group (8.4 vs. 11.3, respectively, P = 0.18). In both groups, the average number of detected SLNs was 1.4 ± 0.5 SLNs per patient (P = 0.74). This study shows that there is no direct benefit of premixing ICG with HSA prior to injection for SLN mapping in breast cancer patients, thereby reducing the cost and complexity of the procedure. With these optimized parameters that eliminate the necessity of HSA, larger trials can now be performed to determine patient benefit.
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Affiliation(s)
- Merlijn Hutteman
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
- Division of Hematology/Oncology, Department of MedicineBeth Israel Deaconess Medical Center, Boston, MA 02215
| | - J. Sven D. Mieog
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | | | - Gerrit-Jan Liefers
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Hein Putter
- Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands
| | - Clemens W.G.M. Löwik
- Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
| | - John V. Frangioni
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215
- Division of Hematology/Oncology, Department of MedicineBeth Israel Deaconess Medical Center, Boston, MA 02215
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Park JS, Choi GS, Kim HJ, Park SY, Park YJ, Lee SW, Xu Z, Bae HI. The Feasibility of an Ex-vivo Sentinel Lymph Mapping Using Preoperative Radioisotope Injection in Cases of Extraperitoneal Rectal Cancer. JOURNAL OF THE KOREAN SOCIETY OF COLOPROCTOLOGY 2011; 27:83-9. [PMID: 21602967 PMCID: PMC3092080 DOI: 10.3393/jksc.2011.27.2.83] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/24/2011] [Accepted: 04/13/2011] [Indexed: 11/01/2022]
Abstract
PURPOSE The purpose of this research was to evaluate the feasibility of sentinel lymph node (SLN) mapping involving transanal injection with an ex-vivo mapping in patients with rectal cancer. METHODS Between April 2007 and December 2009, 20 consecutive patients with T1-3, N0-1 clinical stage rectal cancer preoperatively underwent a SLN procedure using submucosal (99m)Tc-phytate injection. All the patients underwent a total mesorectal excision. After the standard surgical resection, all specimens were identified on lymphoscintigraphy, and bench work was done to pick up the sentinel node basin. All the lymph nodes (non-SLNs and SLNs) were examined using conventional hematoxylin and eosin staining and immunohistochemistry with anti-cytokeratin antibodies. RESULTS SLNs were identified from 19 of 20 patients with rectal cancer. The total number of sentinel nodes retrieved from the surgical specimens was 29, and the mean number per patient was 1.6 (range, 0 to 4). In three patients, the SLN was the only positive lymph node. There was one false-negative case with a sensitivity of 88.8% and two upstaged cases (20.0%). The SLN samples from rectal cancer are mainly localized in the pararectal region, but aberrant nodes receive direct drainage from the rectal cancer. On planar lymphoscintigraphy, 15.7% of all patients had aberrant lymphatic drainage to the sigmoid mesenteric or sigmoid lymph node station. CONCLUSION In conclusion, the intraoperative transanal injection for ex-vivo SLN navigation is a safe, feasible surgical modality in patients with rectal cancer. Large studies are warranted to determine the clinical significance of the SLN concept and micrometastasis in rectal cancer.
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Affiliation(s)
- Jun Seok Park
- Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea
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