The synthesis of no-c arrier-added DL-4-[¹⁸F]fluorodeprenyl via the nucleophilic aromatic substitution reaction

No-carrier-added DL-α-methyl-β-4-[¹⁸F]fluorophenyl-N-methyl-N-propy nylethylamine (DL-4-[¹⁸F]fluorodeprenyl) was synthesized via the following 3-step procedure: (1) nucleophilic aromatic substitution by [¹⁸F]fluoride on 4-nitrobenzaldehyde to produce 4-[¹⁸F]fluorobenzaldehyde (yield 65%); (2) the reaction of 4-[¹⁸F]fluorobenzaldehyde with (1-chloro-1-(trimethylsilyl)ethyl)lithium followed by hydrolysis to give 4-[¹⁸F]fluorophenylacetone (yield 50%); and (3) reductive alkylation of 4-[¹⁸F]fluorophenylacetone with N-methyl-propynylamine in the presence of NaBH₃CN (yield 35%) followed by HPLC purification to give a racemic mixture of 4-[¹⁸F]fluorodeprenyl. The overall yield was 11% (EOB corrected), the synthesis time was 90 min and the specific activity >0.57 Ci/μmol (end of synthesis). This synthesis approach, the conversion of an aromatic aldehyde to a homologous methyl ketone, extends the flexibility of the nucleophilic aromatic substitution reaction by applying it to the synthesis of radiotracers which do not bear electron-withdrawing activating groups on the aromatic ring. The tissue distribution of DL-4-[¹⁸F]fluorodeprenyl in mice at 1, 10 and 60 min was also measured and showed that metabolic defluorination was not significant. Clearance of radioactivity from brain after injection of dl-4-[¹⁸F]fluorodeprenyl was more rapid than that previously observed for [¹¹C]L-deprenyl.