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

• Published in: EJNMMI radiopharmacy and chemistry Vol. 2; no. 1; p. 10
• Main Authors: Zirbesegger, Kevin, Buccino, Pablo, Kreimerman, Ingrid, Engler, Henry, Porcal, Williams, Savio, Eduardo
• Format: Journal Article
• Language: English
• Published: England 24.07.2017
• Subjects: Organic precursor; [11C]L-deprenyl-D2; PET radiopharmaceutical; Automated synthesis; L-nordeprenyl-D2
• ISSN: 2365-421X
• DOI: 10.1186/s41181-017-0029-5

The synthesis of [ C]L-deprenyl-D for imaging of astrocytosis with positron emission tomography (PET) in neurodegenerative diseases has been previously reported. [ C]L-deprenyl-D radiosynthesis requires a precursor, L-nordeprenyl-D , 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 organic precursor as free base and automated radiosynthesis of [ C]L-deprenyl-D for PET imaging of astrocytosis. The L-nordeprenyl-D precursor was synthesized from the easily commercial available and cheap reagent L-phenylalanine in five steps. Next, -alkylation of L-nordeprenyl-D free base with [ C]MeOTf was optimized using the automated commercial platform GE TRACERlab® FX C Pro. A simple and efficient synthesis of L-nordeprenyl-D precursor of [ C]L-deprenyl-D 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% (  = 12) (end of synthesis, decay corrected) radiochemical yield from [ C]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 [ C]L-deprenyl-D has been achieved with high purity and specific activity. L-nordeprenyl-D precursor as free amine was applicable for automated production in a commercial synthesis module for preclinical and clinical application.