Synthesis and Evaluation of 18F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging.
Ontology highlight
ABSTRACT: 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 ?-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.
SUBMITTER: Huang S
PROVIDER: S-EPMC6431521 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
ACCESS DATA