Fluorescent agents have been shown to improve intraoperative detection of tumors compared to visual observation. The addition of a radiolabel to a fluorescent agent could improve characterization by enabling cross-validation with nuclear imaging. Radiolabeled somatostatin analogs are ideal candidates for dual-labeling given their proven tumor-targeting properties, though adverse effects of dye conjugation have limited their application. Recently, we developed a bioactive, fluorescent analog of 68Ga-DOTA-TOC using a customized multimodality chelator (MMC) scaffold that minimized the steric effects of dye labeling. Here, we examine the tumor imaging properties of a dual-labeled octreotide analog in somatostatin receptor-2 (SSTR2)-expressing xenografts. Methods: MMC synthesis was performed by attaching an azide-containing pendant arm and an acetate pendant arm to the tetraza chelator, DO2A. Tyr3-octreotide (TOC) was conjugated to MMC on solid-phase, and the resulting peptide conjugate was fluorescently labeled with IRDye800 via copper-free click chemistry to afford MMC(IR800)-TOC. 68Ga labeling was performed using three methods: eluate fractionation, cation exchange with acetone elution, and cation exchange with NaCl elution. Stability was assessed in mouse serum at 37oC for 3 h. PET/CT and near-infrared fluorescence (NIRF) imaging of 68Ga-MMC(IR800)-TOC were conducted in HCT116(SSTR2) tumor-bearing mice at 1, 3 and 24 h. Results: MMC-TOC was synthesized using standard solid-phase techniques and dual labeling was confirmed by HPLC. 68Ga labeling approaches were optimized for buffer concentration and reaction time, and produced comparable crude radiochemical yields (86.7-89.4%). No significant breakdown products or demetalation were observed. PET/CT showed 68Ga-MMC(IR800)-TOC localization in tumors with a tumor-to-muscle ratio of 3.8 (n=3) and high renal clearance. In vivo NIRF imaging at 24 h showed optimal tumor contrast, and ex vivo tissue analysis resulted in ratios of 4.6 (tumor/pancreas) and 8.6 (tumor/muscle) (n=5). Conclusions: Multimodality imaging with a fluorescent 68Ga-DOTA-TOC analog effectively localized SSTR2-expressing tumors and could potentially improve intraoperative detection in patients with neuroendocrine tumors.

Synthesis and in vivo characterization of a 68Ga/NIR labeled peptide for somatostatin receptor targeting

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.