Synthesis and Evaluation of ¹⁸F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging

The gonadotropin-releasing hormone (GnRH) receptor is overexpressed in the majority of tumors of the human reproductive system. The purpose of this study was to develop an ¹⁸F-labeled peptide for tumor GnRH receptor imaging. In this study, the GnRH (pGlu¹-His²-Trp³-Ser⁴-Tyr⁵-Gly⁶-Leu⁷-Arg⁸-Pro⁹-Gly¹⁰-NH₂) peptide analogues FP-d-Lys⁶-GnRH (FP = 2-fluoropropanoyl) and NOTA-P-d-Lys⁶-GnRH (P = ethylene glycol) were designed and synthesized. The IC₅₀ values of FP-d-Lys⁶-GnRH and NOTA-P-d-Lys⁶-GnRH were 2.0 nM and 56.2 nM, respectively. 4-Nitrophenyl-2-[¹⁸F]fluoropropionate was conjugated to the ε-amino group of the d-lysine side chain of d-Lys⁶-GnRH to yield the new tracer [¹⁸F]FP-d-Lys⁶-GnRH with a decay-corrected yield of 8 ± 3% and a specific activity of 20-100 GBq/µmol (n=6). Cell uptake studies of [¹⁸F]FP-d-Lys⁶-GnRH in GnRH receptor-positive PC-3 cells and GnRH receptor-negative CHO-K1 cells indicated receptor-specific accumulation. Biodistribution and PET studies in nude mice bearing PC-3 xenografted tumors showed that [¹⁸F]FP-d-Lys⁶-GnRH was localized in tumors with a higher uptake than in surrounding muscle and heart tissues. Furthermore, the metabolic stability of [¹⁸F]FP-d-Lys⁶-GnRH was determined in mouse blood and PC-3 tumor homogenates at 1 h after tracer injection. The presented results indicated a potential of the novel tracer [¹⁸F]FP-d-Lys⁶-GnRH for tumor GnRH receptor imaging.