TY - JOUR
T1 - Specific targeting of somatostatin receptor subtype-2 for fluorescence-guided surgery
AU - Vargas, Servando Hernandez
AU - Kossatz, Susanne
AU - Voss, Julie
AU - Ghosh, Sukhen C.
AU - Tran Cao, Hop S.
AU - Simien, Jo
AU - Reiner, Thomas
AU - Dhingra, Sadhna
AU - Fisher, William E.
AU - Azhdarinia, Ali
N1 - Funding Information:
This work was supported by the National Institute of Biomedical Imaging and Bioengineering (R01 EB017279), NCI (P30 CA008748, K99 CA218875-01A1), the Tow Foundation, and Memorial Sloan Kettering Cancer Center's Center for Molecular Imaging & Nanotechnology. The authors thank Martina Cagigas and Amy McElhany for assistance with surgical biospecimens, and Dr. Erik Wilson and Armando Garcia for access to the Memorial Hermann Surgical Innovation and Robotics Institute. The authors also acknowledge the support of the Imaging Core Facility at The University of Texas Health Science Center– Center for Molecular Imaging, and the Radiochemistry and Molecular Imaging Probes Core Facility and Molecular Cytology Core Facility at Memorial Sloan Kettering Cancer Center.
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019
Y1 - 2019
N2 - Purpose: Clinically available intraoperative imaging tools to assist surgeons in identifying occult lesions are limited and partially responsible for the high rate of disease recurrence in patients with neuroendocrine tumors (NET). Using the established clinical efficacy of radiolabeled somatostatin analogs as a model, we demonstrate the ability of a fluorescent somatostatin analog to selectively target tumors that overexpress somatostatin receptor subtype-2 (SSTR2) and demonstrate utility for fluorescence-guided surgery (FGS). Experimental Design: A multimodality chelator (MMC) was used as a "radioactive linker" to synthesize the fluores-cently labeled somatostatin analog, 67/68Ga-MMC(IR800)-TOC. In vivo studies were performed to determine the pharmacokinetic profile, optimal imaging time point, and specificity for SSTR2-expressing tissues. Meso- and microscopic imaging of resected tissues and frozen sections were also performed to further assess specific binding, and binding to human NETs was examined using surgical biospecimens from patients with pancreatic NETs. Results: Direct labeling with 67Ga/68Ga provided quantitative biodistribution analysis that was in agreement with fluorescence data. Receptor-mediated uptake was observed in vivo and ex vivo at the macro-, meso-, and microscopic scales. Surgical biospecimens from patients with pancreatic NETs also displayed receptor-specific agent binding, allowing clear delineation of tumor boundaries that matched pathology findings. Conclusions: The radioactive utility of the MMC allowed us to validate the binding properties of a novel FGS agent that could have a broad impact on cancer outcomes by equipping surgeons with real-time intraoperative imaging capabilities.
AB - Purpose: Clinically available intraoperative imaging tools to assist surgeons in identifying occult lesions are limited and partially responsible for the high rate of disease recurrence in patients with neuroendocrine tumors (NET). Using the established clinical efficacy of radiolabeled somatostatin analogs as a model, we demonstrate the ability of a fluorescent somatostatin analog to selectively target tumors that overexpress somatostatin receptor subtype-2 (SSTR2) and demonstrate utility for fluorescence-guided surgery (FGS). Experimental Design: A multimodality chelator (MMC) was used as a "radioactive linker" to synthesize the fluores-cently labeled somatostatin analog, 67/68Ga-MMC(IR800)-TOC. In vivo studies were performed to determine the pharmacokinetic profile, optimal imaging time point, and specificity for SSTR2-expressing tissues. Meso- and microscopic imaging of resected tissues and frozen sections were also performed to further assess specific binding, and binding to human NETs was examined using surgical biospecimens from patients with pancreatic NETs. Results: Direct labeling with 67Ga/68Ga provided quantitative biodistribution analysis that was in agreement with fluorescence data. Receptor-mediated uptake was observed in vivo and ex vivo at the macro-, meso-, and microscopic scales. Surgical biospecimens from patients with pancreatic NETs also displayed receptor-specific agent binding, allowing clear delineation of tumor boundaries that matched pathology findings. Conclusions: The radioactive utility of the MMC allowed us to validate the binding properties of a novel FGS agent that could have a broad impact on cancer outcomes by equipping surgeons with real-time intraoperative imaging capabilities.
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U2 - 10.1158/1078-0432.CCR-18-3312
DO - 10.1158/1078-0432.CCR-18-3312
M3 - Article
C2 - 31015345
AN - SCOPUS:85069054689
SN - 1078-0432
VL - 25
SP - 4332
EP - 4342
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -