Remote controlled one-step production of 18F labeled butyrophenone neuroleptics exemplified by the synthesis of n.c.a. [ 18F] N-methylspiperone

Abstract

A remote controlled synthesis for the routine production of [ 18F]butyrophenones is described. The modular set-up includes a one step HPLC- and a solid phase extraction unit both connected on-line to a single unit reactor. [ 18F]N-methylspiperone was synthesized from 8-[4-(4-nitrophenyl)-4-oxobutyl]-3-methyl-1-phenyl-1,3,8-triazaspiro [4.5]decan-4-one using the direct nucleophilic aromatic fluorination in presence of a cryptate consisting of Kryptofix® 2.2.2, potassium oxalate and a small amount of potassium carbonate (50 μg). The one-step synthesis gave radiochemical yields of 15–20% within a synthesis time of 70 min, including product formation. Starting with the appropriate amount of 18F-fluoride up to 180 mCi [ 18F]MSP have been obtained. The radiochemical purity is in the range of 96–98% and the specific activity is >4000 Ci/mmol. The system is generally useful for the synthesis of other n.c.a. [ 18F]butyrophenone neuroleptics such as [ 18F]N-methylbenperidol starting with the corresponding nitro precursors.