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

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.

Preclinical evaluation and pilot clinical study of [18F]AlF-labeled FAPI-tracer for PET imaging of cancer associated fibroblasts

“…The n- octanol/PBS partition coefficients of [ 18 F]AlF-P-FAPI, [ 18 F]FAPI-42, and [ 68 Ga]Ga-FAPI-04 were determined, as previously described 25 .…”

Novel 18F-Labeled Isonicotinamide-Based Radioligands for Positron Emission Tomography Imaging of Glycogen Synthase Kinase-3β

“…The percentage of unchanged radioactivity for [ 18 F]10a−d in plasma was determined by a previously reported method. 31 In vivo metabolic analysis of [ 18 F]10a−d in plasma was performed using rat blood samples (0.5 mL) that were collected at 5, 10, 15, and 30 min after tracer injection. The blood was mixed with MeCN (0.5 mL) and centrifuged (12,000g, 10 min).…”

Preclinical Evaluation and Pilot Clinical Study of 18F-AlF-labeled FAPI-Tracers for PET Imaging of Cancer Associated Fibroblasts

“…High-resolution mass spectrometry (HRMS) data were acquired using a Thermo Fisher Scienti c Orbitrap Fusion mass spectrometer (Thermo Fisher Scienti c, San Jose, CA, USA). The synthesis of non-radioactive compounds, which includes reference compounds 19 F-P-FAPI and 19 F-FAPI-42, and their precursors are described in detail in Supplementary Schemes S1 and S2.…”

“…The n-octanol/PBS partition coefficients of 18 F-P-FAPI, 18 F-FAPI-42, and 68 Ga-FAPI-04 were determined, as previously described [19].…”

“…The labeling precursors (P-FAPI and NOTA-FAPI-42) and reference compounds ( 19 F-FAPI-42 and 19 F-P-FAP) were successfully prepared using high chemical purity (>95%) and identi ed through the use of mass spectrometry (Supplementary data). 18 F-labeled FAP tracers ( 18 F-FAPI-42 and 18 F-P-FAP) were successfully prepared in automated manner via…”