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. ­e 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. ­e 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 speci¢c 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-speci¢c 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-DLys6 -GnRH was determined in mouse blood and PC-3 tumor homogenates at 1 h after tracer injection. ­e presented results indicated a potential of the novel tracer [18F]FP-D-Lys6 -GnRH for tumor GnRH receptor imaging.