An efficient preparation of labelling precursor of [(11)C]L-deprenyl-D(2) and automated radiosynthesis

BACKGROUND: The synthesis of [(11)C]L-deprenyl-D(2) for imaging of astrocytosis with positron emission tomography (PET) in neurodegenerative diseases has been previously reported. [(11)C]L-deprenyl-D(2) radiosynthesis requires a precursor, L-nordeprenyl-D(2), which has been previously synthesized from L-amphetamine as starting material with low overall yields. Here, we present an efficient synthesis of L-nordeprenyl-D(2) organic precursor as free base and automated radiosynthesis of [(11)C]L-deprenyl-D(2) for PET imaging of astrocytosis. The L-nordeprenyl-D(2) precursor was synthesized from the easily commercial available and cheap reagent L-phenylalanine in five steps. Next, N-alkylation of L-nordeprenyl-D(2) free base with [(11)C]MeOTf was optimized using the automated commercial platform GE TRACERlab® FX C Pro. RESULTS: A simple and efficient synthesis of L-nordeprenyl-D(2) precursor of [(11)C]L-deprenyl-D(2) as free base has been developed in five synthetic steps with an overall yield of 33%. The precursor as free base has been stable for 9 months stored at low temperature (−20 °C). The labelled product was obtained with 44 ± 13% (n = 12) (end of synthesis, decay corrected) radiochemical yield from [(11)C]MeI after 35 min synthesis time. The radiochemical purity was over 99% in all cases and specific activity was (170 ± 116) GBq/μmol. CONCLUSIONS: A high-yield synthesis of [(11)C]L-deprenyl-D(2) has been achieved with high purity and specific activity. L-nordeprenyl-D(2) precursor as free amine was applicable for automated production in a commercial synthesis module for preclinical and clinical application.