Iodine‐123 labeled derivatives of methylphenidate: Potential SPECT radiopharmaceuticals for brain dopamine transporters

Abstract

Since dl-threo-[ 11 C]methylphenidate (Ritalin) and especially the more active enantiomer, d-threo-[ 11 C]methylphenidate, have favorable properties for PET studies,we prepared two radioiodinated analogs of methylphenidate, p-[ 123 I]icdomethylphenidate and m-[ 123 I]iodo-p-hydroxymethylphenidate with a view to evaluating them as potential SPECT tracers. To prepare p-[ 123 I]iodomethylphenidate, the p-tributyltin derivative was prepared from the previously reported p-bromomethylphenidate and reacted under acidic conditions with I-123 iodide plus chloramine-T at room temperature for 90 seconds. The predominant radioactive product was obtained in 85% radiochemical yield and >10 Ci/μmol specific radioactivity after HPLC purification. It had the same HPLC retention time as a spectroscopically characterized non-radioactive p-iodomethylphenidate standard prepared via nitration of methylphenidate and diazotization, after protection of the secondary amino group by benzoylation. A second radioiodinated methylphenidate derivative, m-[ 123 I]iodo-p-hydroxymethylphenidate was prepared in 80% radiochemical yield by direct iodination of the known p-hydroxymethylphenidate. In this case the non-radioactive standard was prepared by iodination of p-hydroxyritalinic acid using I 2 and iodic acid, followed by esterification