An updated synthesis of N1′‐([11C]methyl)naltrindole for positron emission tomography imaging of the delta opioid receptor

A new method for the synthesis of the highly selective delta opioid receptor (DOR) antagonist radiotracer N1 '-([11 C]methyl)naltrindole ([11 C]MeNTI) is described. The original synthesis required hydrogentation of a benzyl protecting group after 11 C-labeling, which is challenging in modern radiochemistry laboratories that tend to be heavily automated and operate according to current Good Manufacturing Practice. To address this challenge we describe development of a novel MeNTI precursor bearing a methoxymethyl acetal (MOM) protecting group which is easily removed with HCl, and employ it in an updated synthesis of [11 C]MeNTI. The new synthesis is fully automated and validated for clinical use. The total synthesis time is 45 min and provides [11 C]MeNTI in good activity yield (49 ± 8 mCi), molar activity (3926 ± 326 Ci/mmol) and radiochemical purity (97 ± 2%).