Comparisons of 2-[18F]-ADAM, 4-[18F]-ADAM and [18F]AFM as SERT imaging agents in rats using μPET

Objectives N,N-Dimethyl-2-(2-amino-4-[¹⁸F]fluorophenylthio)benzylamine (4-[¹⁸F]-ADAM, 1) and 2-[2-(dimethylaminomethyl)phenylthio]-5-[¹⁸F]fluoromethylphenylamine ([¹⁸F]AFM, 2) are potent SERT imaging agents (Shiue, 03; Huang, 05). We report herein the direct comparisons of 1, 2 and N,N-dimethyl-2-(2-[¹⁸F]fluoro-4-aminophenylthio)benzylamine (2-[¹⁸F]-ADAM, 3) as SERT imaging agents in rats using μPET.

Methods Both 1 and 3 were synthesized by reacting N,N-dimethyl-2-(2,4-dinitrophenylthio)benzylamine with K[¹⁸F]/K_2.2.2 @ 120⁰C for 10 min followed by reduction with NaBH₄/Cu(OAc)₂ at 80⁰C and purification with HPLC. Compound 2 was synthesized by the reported method (Huang et al., 05). Male S-D rats and micro-PET R4 scanner were used for the experiments. The data were expressed as %ID/g and the Specific Uptake Ratios (SURs) were expressed as (target – cerebellum)/cerebellum.

Results The radiochemical yield of 1, 2 and 3 were ~6, 1 and 14%, respectively. Synthesis time:120 min. Specific activity:3 Ci/μmol. The log P of 1, 2 and 3 were 2.73, 2.44 and 1.34, respectively. μPET studies showed that the uptake of 1, 2 and 3 in midbrain were 0.87, 1.08 and 0.43 %ID/g, respectively, and both 1 and 2 had high specific uptake in brain regions rich in SERT while 3 had no specific uptake in rat brain. The max SUR for midbrain, hypothalamus, striatum, hippocampus and frontal cortex were 3.95, 3.81, 3.83, 2.36 and 2.36, respectively, 83 min post-injection of 1. The corresponding values for 2 were 2.28, 2.20, 1.85, 1.21 and 1.22 at 55 min post-injection.

Conclusions Both 1 and 2 are potent SERT imaging agents, although the radiochemical yield of 2 is too low for practical applications. In contrast, 3 is not a useful SERT imaging agent.

Research Support National Science Council of Taiwan, Grants NSC 97-2321-B-016-002,NSC 97-2811-B-016-005.