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

Abstract

BackgroundThe 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.ResultsA 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.ConclusionsA 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.

Molecular Imaging of Monoamine Oxidase A Expression in Highly Aggressive Prostate Cancer: Synthesis and Preclinical Evaluation of Positron Emission Tomography Tracers

“…To obtain the analytical standard of [ 11 C]­clorgyline, compound 5 , the next step was performed according to the reaction between N -methylpropargylamine and compound 2 , obtaining a 66% yield (condition e, Scheme ). To synthesize the labeling precursor nor-clorgyline 4 , we explored a methodology that would minimize competitive reactions of polyalkylation on derivative 2 . Using the solid-phase Staudinger’s methodology from azide derivatives and triphenylphosphine resin, followed by N -alkylation and subsequent cleavage, efficiently yielded secondary amines .…”

“…Here, we performed the radiolabeling using the more reactive [ 11 C]­methyl trifluoromethanesulfonate ([ 11 C]­MeOTf) (Scheme ) and a purification method based on our previous reports (see the Experimental Section). , The fully automated synthesis of [ 11 C] 5 was performed using the commercial platform GE TRACERlab FX C Pro (Figure S6). This methodology afforded us the potential of [ 11 C]­MeOTf in the improvement and reproducibility of radiochemical yields.…”

“…The structure of compounds was confirmed using analytical and spectroscopic techniques, such as 1 H NMR mono and bidimensional, 13 48 Here, we performed the radiolabeling using the more ) and a purification method based on our previous reports (see the Experimental Section). 45,49 The fully automated synthesis of [ 11 C]5 was performed using the commercial platform GE TRACERlab FX C Pro (Figure S6). This methodology afforded us the potential of [ 11 C-methylating agent.…”