Facile radiosynthesis of new carbon-11-labeled propanamide derivatives as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging

Abstract

The androgen receptor (AR) is an attractive target for the treatment and molecular imaging of prostate cancer. New carbon-11-labeled propanamide derivatives were first designed and synthesized as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging using the biomedical imaging technique positron emission tomography (PET). The target tracers, (S)- N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-[ 11C]methoxyphenoxy)-2-methylpropanamide ([ 11C] 8a), ( S)-2-hydroxy-3-(2-[ 11C]methoxyphenoxy)-2-methyl- N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([ 11C] 8e), ( S)- N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(4-[ 11C]methoxyphenoxy)-2-methylpropanamide ([ 11C] 8c) and ( S)-2-hydroxy-3-(4-[ 11C]methoxyphenoxy)-2-methyl- N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([ 11C] 8g), were prepared by O-[ 11C]methylation of their corresponding precursors, ( S)- N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-hydroxyphenoxy)-2-methylpropanamide ( 9a), ( S)-2-hydroxy-3-(2-hydroxyphenoxy)-2-methyl- N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ( 9b), ( S)- N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methylpropanamide ( 9c) and ( S)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methyl- N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ( 9d), with [ 11C]CH 3OTf under basic conditions and isolated by a simplified C-18 solid-phase extraction (SPE) method in 55 ± 5% ( n = 5) radiochemical yields based on [ 11C]CO 2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol ( n = 5).