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Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery
Servando Hernandez Vargas1, Susanne Kossatz2, Julie Voss1
1The Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas.
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 fluorescently 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.
Insights
A novel fluorescent somatostatin analog targets neuroendocrine tumors (NETs) overexpressing SSTR2, enabling precise tumor boundary delineation for fluorescence-guided surgery (FGS). This advancement aids surgeons in identifying occult lesions, potentially reducing disease recurrence.
Area of Science:
- Oncology
- Medical Imaging
- Radiochemistry
Background:
- Limited intraoperative imaging tools contribute to high recurrence rates in neuroendocrine tumor (NET) patients.
- Radiolabeled somatostatin analogs are clinically effective for NET imaging.
- Somatostatin receptor subtype-2 (SSTR2) is overexpressed in many NETs.
Purpose of the Study:
- To develop and evaluate a fluorescent somatostatin analog for fluorescence-guided surgery (FGS).
- To demonstrate selective tumor targeting in SSTR2-expressing NETs.
- To assess the utility of FGS in improving intraoperative lesion identification.
Main Methods:
- Synthesis of a fluorescent somatostatin analog, 67/68Ga-MMC(IR800)-TOC, using a multimodality chelator (MMC).
- In vivo pharmacokinetic and specificity studies in SSTR2-expressing tissues.
- Ex vivo macro-, meso-, and microscopic imaging of resected tissues and patient biospecimens.
Main Results:
- Fluorescence data correlated with quantitative biodistribution analysis from direct 67Ga/68Ga labeling.
- Receptor-mediated uptake was confirmed in vivo and ex vivo across multiple scales.
- The agent specifically bound to human pancreatic NET biospecimens, accurately delineating tumor margins.
Conclusions:
- The developed fluorescent somatostatin analog effectively targets SSTR2-expressing NETs.
- This agent enables real-time intraoperative imaging for improved tumor boundary delineation.
- The validated FGS agent holds potential to significantly impact cancer outcomes by enhancing surgical precision.
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