Introduction
There has been considerable interest in the development of PET radioligands that are useful for imaging serotonin transporters (SERT) in the living human brain. Recently, N,N-dimethyl-2-(arythio)benzylamines have been labelled with 11C and 18F as promising SERT PET radioligands1, 2, 3, 4, 5, 6, 7. One of them is 4-[18F]-ADAM (1) 2 and the other is N,N-dimethyl-2-(2-amino-4-trifluoromethylphenylthio)benzylamine 7 . The N-methyl-2-(2-amino-4-trifluoromethylphenylthio)benzylamine has been shown to be less lipophilic, but has higher brain uptake in rat than its N,N-dimethyl counterpart 7 . The purpose of this study was to synthesize N-methyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (3) and compare it with compound 1 as a SERT imaging agent.
Methods
N-methyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (3) was synthesized by nucleophilic substitution of the multi-step synthesized N-methyl-2-(2,4-dinitrophenylthio)benzylamine (2) with K[18F]/Kryptofix 2.2.2 in DMSO at 130 degree C for 25 minutes followed by reduction with NaBH4-Cu(OAc)2 in EtOH at 78 degree C for 20 minutes and purification with HPLC (10 × 250 mm, Phenomenex Luna 2; CH3CN:0.1 M HCO2NH4 (30:70) containing 0.3 v% of acetic acid; 5 ml/min).
Results
N-methyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (3) was synthesized in ∼ 5–10% yield with a synthesis time of 150 minutes from EOB. The radiochemical purity was > 97%, and the specific activity was 0.5–1 Ci/μmol. The radiochemical yield of compound 3 was similar to that of compound 1.
Conclusion
N-methyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (3) has been synthesized in moderate yield with high radiochemical yield and specific activity. The pharmacological profile of this agent is under investigation.