Flourine-18 labeling of electron-rich 5-HT2A agonists

Objectives There is one known 5-HT2A agonist tracer; [11C]- CIMBI-36. We aimed to develop a flouirne-18 version of this tracer. CIMBI-36 is metabolized in the 5-postion. Therefore we wanted to investigate possibilities to change the methoxy group to fluorine both for labeling purposes and metabolic stability.

Methods We envisaged that the labeled amine could be obtained via hypervalent iodonium salts. The labeling of this compound though did not give consistent high yields. Therefore we continued with preparation of the spirocylic iodonium ylides.

Results This was success fully labeled high yield, up to 87 % indicated by TLC. The amine was then deprotected and reacted with to different aldehydes and purified. [18F]-3 was prepared form the iodonium ylide of the already N-BOMe precursor as the methylenedioxy moiety was not stable under the applied conditions.

Conclusions Compound 1 was tested in vivo in Danish landrace pigs as the carbon-11 version and compound 2 and 3 as the fluorine 18 version. All compounds showed high brain uptake, reversible kinetics and good separation between cortex and cerebellum. Unfortunately they had even higher uptake in thalamus and no effect of challenge with ketanserin was observed. This is probably due to off target binding. $$graphic_BF939748-4135-4698-AF54-0C23478B8651$$