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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  18 F-labeled peptide for tumor GnRH receptor imaging. In this study, the GnRH (pGlu 1 -His 2 -Trp 3 -Ser 4 -Tyr 5 -Gly 6 -Leu 7 -Arg 8 -Pro 9 -Gly 10 -NH 2 ) peptide analogues FP- d -Lys 6 -GnRH (FP = 2-fluoropropanoyl) and NOTA-P- d -Lys 6 -GnRH ( P  = ethylene glycol) were designed and synthesized. The IC 50  values of FP- d -Lys 6 -GnRH and NOTA-P- d -Lys 6 -GnRH were 2.0 nM and 56.2 nM, respectively. 4-Nitrophenyl-2-[ 18 F]fluoropropionate was conjugated to the  ε -amino group of the  d -lysine side chain of  d -Lys 6 -GnRH to yield the new tracer [ 18 F]FP- d -Lys 6 -GnRH with a decay-corrected yield of 8 ± 3% and a specific activity of 20−100 GBq/ µ mol ( n =6). Cell uptake studies of [ 18 F]FP- d -Lys 6 -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 [ 18 F]FP- d -Lys 6 -GnRH was localized in tumors with a higher uptake than in surrounding muscle and heart tissues. Furthermore, the metabolic stability of [ 18 F]FP- d -Lys 6 -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 [ 18 F]FP- d -Lys 6 -GnRH for tumor GnRH receptor imaging.

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

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