Synthesis of [F-18]FA-4 and [C-11]pipzA-4 as radioligands for the high affinity choline uptake system

We have prepared two radiolabelled analogues of hemicholinium-3 (HC-3) as p otential in vivo tracers of the sodium dependent high affinity choline upta ke (SDHAChU) system. Thus, 4-[1-hydroxy-2-(4-[F-18] fluoromethylpiperidinyl )ethyl]-4'-[1-hydroxy-2-(4-methylpiperidinyl)ethyl] ([F-18]FA-4) and 4-[1-h ydroxy-2-(4-[ C-11] methylpiperazinyl)ethyl]-4'-[1-hydroxy-2-(4-methylpiper idinyl)]biphenyl ([C-11]pipzA-4) have been synthesized. [F-18]FA-4 was prep ared by reaction of 4-[F-18] fluoromethylpiperidine with 4-(alpha-bromoacet yl)-4'-(4-methylpiperidinyl acetyl)biphenyl followed by reduction of the ke to groups to alcohols with: NaBH4. The total synthesis time was 300 minutes and [18F]FA-4 was Obtained with a specific activity of 5.6 GBq/mu mol (EOS ) and an overall decay corrected radiochemical yield of 3.1+/-0.6%. [C-11]p ipzA-4 was prepared by reaction of [C-11]methyl triflate with 4-[1 -hydroxy -2-piperazinyl)ethyl]-4'-[1-hydroxy-2-(4-methylpiperidinyl)ethyl]- biphenyl . The total synthesis time was 25 minutes and [C-11]pipzA-4 was obtained wi th:a specific activity of 13.7 GBq/mu mol (EOS) and an overall decay correc ted radiochemical yield of 19.5+/-2.2%.