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

Contrast Media Mol Imaging. 2019 Mar 7:2019:5635269. doi: 10.1155/2019/5635269. eCollection 2019.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Fluorine Radioisotopes / chemistry*
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Nude
  • PC-3 Cells
  • Peptides / chemistry*
  • Positron-Emission Tomography / methods*
  • Prostatic Neoplasms / diagnostic imaging
  • Prostatic Neoplasms / metabolism
  • Receptors, LHRH / metabolism*

Substances

  • Fluorine Radioisotopes
  • Peptides
  • Receptors, LHRH