Synthesis and preclinical evaluation of 6-[18F]Fluorine-Alpha-Methyl-L-Tryptophan, a novel PET tracer for measuring tryptophan uptake.

The Positron emission tomography (PET) radioligand alpha-[11C]Methyl-L-tryptophan ([11C]AMT) has been used to assess tryptophan metabolism in cancer, epilepsy, migraine and autism. Despite the extensive application, the utility of this tracer is currently hampered by the short half-life of the radionuclide used for its labeling (11C, t1/2 = 20.4 min). We herein report the design, synthesis, radiolabeling and initial in vivo evaluation of a fluorine-18 (18F, t1/2 = 109.7 min) labeled analog that is fluorinated in the 6-position of the aromatic ring ([18F]6-F-AMTr). In a head-to-head comparison between [18F]6-F-AMTr and [11C]AMT in mice using PET, peak brain radioactivity, regional brain distribution and kinetic profiles were similar be-tween the two tracers. [18F]6-F-AMTr was however not a substrate for IDO1 nor TPH as determined in in vitro enzymatic assays. The brain uptake of the tracer is thus more likely related to LAT1 transport over the blood-brain barrier than metabolism along the serotonin or kynurenine pathways.