Synthesis and in vitro evaluation of small-molecule [18F] labeled gonadotropin-releasing hormone (GnRH) receptor antagonists as potential PET imaging agents for GnRH receptor expression

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Abstract

Two novel small molecule gonadotropin-releasing hormone (GnRH) receptor antagonists (12 and 13) of the furamide-class were synthesized and evaluated in vitro for their receptor binding affinities for the rat GnRH receptor. Radiolabeling with no carrier added fluorine-18 of the appropriate precursors was investigated in a one-step reaction. Log P (Octanol/PBS pH 7.4) and serum stability of the compounds were investigated. The antagonists showed low nM affinity for the rat GnRH receptor. 18F-radiolabled compounds were obtained in high radiochemical purity (>95%) and specific activity (>75 GBq/μmol). These findings suggest this class of compounds holds promise as potential probes for PET targeting of GnRH-receptor expression.

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Acknowledgments

This research was supported by the Norwegian Cyclotron Center AS (NMS AS), Norwegian Research Council (199529) the Office of Science, United States Department of Energy, DE-SC0002061 and in part from NIH (Grant No. RR11973). The authors would like to thank Nadine Bauer and the staff of CMGI (L. Planutyte and D. Kukis) for their assistance. We would further extend our gratitude to Prof. Kevin Pfleger and Karin A. Eidne for supplying full-length rat GnRH-R cDNA vector.

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