Radiosynthesis of Carbon-11 Labeled Puromycin as a Potential PET Candidate for Imaging Protein Synthesis in Vivo.

In order to address the limitations associated with the present range of PET radiotracers used for imaging protein synthesis in vivo we have synthesized a candidate PET radiotracer based on Puromycin (3, PURO), a protein synthesis inhibitor. The desmethylPURO 9 precursor for radiolabeling with carbon-11 radioisotope was synthesized in two steps employing EDC/HOBt amide coupling in overall 76% yield. Optimal conditions for radiolabeling were then established via methylation/deprotection sequence. Under these conditions as determined by NMR analysis 9 showed partial stability (ca. 80%) under acidic conditions. Limited evidence of stereochemical stability of 3 was also found. The radiolabeling of intermediate [(11)C]12 was accomplished with up to 57% conversion from [(11)C]iodomethane. An automated method was then developed for high radioactivity radiosynthesis to produce [(11)C]3 ([(11)C]PURO) in 16 ± 6% (n = 3) decay corrected radiochemical yields.