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Dual-Labeled PSMA-Targeting Agent for Preoperative Molecular Imaging and Fluorescence-Guided Surgery for Prostate Cancer.

The objective of this study was to report the synthesis and characteristics of a dual modality imaging agent, Tc-99m GRFLTGGTGRLLRIS-GHEG-ECG-K(-5-carboxy-X-rhodamine)-NH2 (GRFLT-ECG-ROX), and to verify its feasibility as both molecular imaging and intra-operative guidance agent. GRFLT-ECG-ROX was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of GRFLT-ECG-ROX with Tc-99m was accomplished using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution and ex vivo imaging studies were performed using LNCaP and PC-3 tumor-bearing murine models. Surgical removal of tumor nodules in murine models with peritoneal carcinomatosis was performed under a fluorescence imaging system. After radiolabeling procedures with Tc-99m, Tc-99m GRFLT-ECG-ROX complexes were prepared in high yield (> 96%). The binding affinity value (Kd ) of Tc-99m GRFLT-ECG-ROX for LNCaP cells was estimated to be 9.5 ± 1.3 nM. In gamma camera imaging, the tumor to normal muscle uptake ratios of Tc-99m GRFLT-ECG-ROX increased with time (3.1 ± 0.2, 4.0 ± 0.4, and 6.3 ± 0.9 at 1, 2, and 3 h, respectively). Under real-time optical imaging, the removal of visible nodules was successfully performed. Thus, Tc-99m GRFLT-ECG-ROX could provide both pre-operative molecular imaging and fluorescence imaging guidance for tumor removal.