3-Amino-4-(2-((4-[~(18)F]fluorobenzyl)methyIamino)methylphenylsulfanyl)benzonitrile,an F-18 Fluorobenzyl Analogue of DASB:Synthesis,in Vitro Binding,and in Vivo Biodistribution Studies

摘要

3-Amino-4-(2[~(11)C]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-[~(18)F]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-arnino-4-(2-aminomethylphenylsulfanyl)benzonitrile and related analogues.In addition,we report our results from incorporating p-[~(18)F]fluorobenzyl iodide in DASB precursor and its affect on the in vitro and in vivo biological properties of the DASB.