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

Article abstract of DOI:10.1002/(SICI)1099-1344(19991230)42:13<1289::AID-JLCR287>3.0.CO;2-C

We have prepared two radiolabelled analogues of hemicholinium-3 (HC-3) as potential in vivo tracers of the sodium dependent high affinity choline uptake (SDHAChU) system. Thus, 4-[1-hydroxy-2-(4-[¹⁸F]fluoromethylpiperidinyl)ethyl]-4'-[1-hydroxy-2-(4 -methylpiperidinyl)ethyl]biphenyl ([¹⁸F]FA-4) and 4-[1-hydroxy-2-(4-¹¹C]methylpiperazinyl)ethyl]-4'-[1-hydroxy-2-(4 -methylpiperidinyl)]biphenyl ([¹¹C]pipzA-4) have been synthesized. [¹⁸F]FA-4 was prepared by reaction of 4-[¹⁸F]fluoromethylpiperidine with 4-(α-bromoacetyl)-4'-(4-methylpiperidinylacetyl)biphenyl followed by reduction of the keto 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/μmol (EOS) and an overall decay corrected radiochemical yield of 3.1 ± 0.6%. [¹¹C]pipzA-4 was prepared by reaction of [¹¹C]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 [¹¹C]pipzA-4 was obtained with a specific activity of 13.7 GBq/μmol (EOS) and an overall decay corrected radiochemical yield of 19.5 ± 2.2%.