An efficient preparation of labelling precursor of [¹¹C]L-deprenyl-D₂ and automated radiosynthesis

The synthesis of [¹¹C]L-deprenyl-D₂ for imaging of astrocytosis with positron emission tomography (PET) in neurodegenerative diseases has been previously reported. [¹¹C]L-deprenyl-D₂ radiosynthesis requires a precursor, L-nordeprenyl-D₂, which has been previously synthesized from L-amphetamine as starting material with low overall yields. Here, we present an efficient synthesis of L-nordeprenyl-D₂ organic precursor as free base and automated radiosynthesis of [¹¹C]L-deprenyl-D₂ for PET imaging of astrocytosis. The L-nordeprenyl-D₂ precursor was synthesized from the easily commercial available and cheap reagent L-phenylalanine in five steps. Next, N-alkylation of L-nordeprenyl-D₂ free base with [¹¹C]MeOTf was optimized using the automated commercial platform GE TRACERlab® FX C Pro.

A simple and efficient synthesis of L-nordeprenyl-D₂ precursor of [¹¹C]L-deprenyl-D₂ 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 [¹¹C]MeI after 35 min synthesis time. The radiochemical purity was over 99% in all cases and specific activity was (170 ± 116) GBq/μmol.

A high-yield synthesis of [¹¹C]L-deprenyl-D₂ has been achieved with high purity and specific activity. L-nordeprenyl-D₂ precursor as free amine was applicable for automated production in a commercial synthesis module for preclinical and clinical application.