Structure-localization relationships of ¹¹C-labeled phentermine derivatives: Effect of aromatic substitution

A series of phentermine analogs, including the unsubstituted, the para-F, -Cl, -Br and -I, and the meta-CF₃ derivatives, were labeled by [¹¹C]methylation and evaluated in rats to determine the structure-localization relationships for this class of regional cerebral blood flow imaging agents. All the phentermines were well-localized in the brain; however, only the para-substituted agents were well-retained. Localization in the nontarget tissue was affected by the lipophilicity of the substituent. Comparison with the radioiodinated analogs showed virtually identical results, which suggests that the compounds were not significantly metabolized. The agent with the best biodistribution characteristics was the N-[¹¹C]methyl-p-iodophentermine, with the p-bromo analog almost equivalent.