In vivo biodistribution of an androgen receptor avid PET imaging agent 7-alpha-fluoro-17 alpha-methyl-5-alpha-dihydrotestosterone ([(18)F]FMDHT) in rats pretreated with cetrorelix, a GnRH antagonist.

PURPOSE: For this study, we have assessed the in vivo distribution and androgen receptor (AR) seeking properties of an F-18-labeled androgen [(18)F]FMDHT in rats castrated with a GnRH antagonist. MATERIALS AND METHODS: The radiochemical synthesis of [(18)F]FMDHT was performed using a previously published method. The radiochemical synthesis provided the desired product in good radiochemical yields and radiochemical purity. In vivo biodistribution studies were performed in chemically castrated rats. The animals were castrated using cetrorelix, a GnRH antagonist. To assess the specificity of [(18)F]FMDHT towards ARs, a separate group of animals was pretreated with a large dose of androgen before the [(18)F]FMDHT injection. RESULTS: The in vivo biodistribution results show selective uptake of [(18)F]FMDHT in the prostate that ranged from 0.46 + 0.10 %ID/g at 1 h to 0.59 + 0.16 %ID/g at 3 h with prostate to muscle ratio ranging from 8.06 + 2.46 at 1 h to 18.81 + 4.90 at 3 h. CONCLUSIONS: These in vivo distribution studies document a high selectivity and specificity of [(18)F]FMDHT towards AR rich tissues and suggests that [(18)F]FMDHT may be a useful in vivo PET imaging ligand.

3-Amino-4-(2-((4-[18F]fluorobenzyl)methylamino)methylphenylsulfanyl)benzonitrile, an F-18 fluorobenzyl analogue of DASB: synthesis, in vitro binding, and in vivo biodistribution studies.

3-amino-4-(2[11C]methylaminomethylphenylsulfanyl)benzonitrile (C-11 DASB) exhibits excellent in vitro and in vivo properties toward the serotonin transporter. If labeled with a longer physical half-life radioisotope, this ligand could be more attractive to research groups lacking an on-site cyclotron or lacking C-11 synthesis capabilities. We produce p-[18F]fluorobenzyl iodide on a routine basis to synthesize several neuroimaging agents. Therefore, it was straightforward for us to substitute the DASB precursor with this prosthetic group and assess its biological properties. We designed a different synthesis strategy to obtain the DASB precursor (desmethyl DASB). Herein we report an efficient and facile synthetic route that provides higher chemical yields of 3-amino-4-(2-aminomethylphenylsulfanyl)benzonitrile and related analogues. In addition, we report our results from incorporating p-[18F]fluorobenzyl iodide in DASB precursor and its affect on the in vitro and in vivo biological properties of the DASB.