Discovery of 7-18FFluorotryptophan as a Novel Positron Emission Tomography (PET) Probe for the Visualization of Tryptophan Metabolism in Vivo

Tryptophan and its metabolites are involved in different physiological and pathophysiological processes. Consequently, positron emission tomography (PET) tracers addressing tryptophan metabolic pathways should allow the detection of different pathologies like neurological disorders and cancer. Herein we report an efficient method for the preparation of fluorotryptophans labeled in different positions with 18F and their biological evaluation. 4-7-18FFluorotryptophans (18FFTrps) were prepared according to a modified protocol of alcohol-enhanced Cu-mediated radiofluorination in 30-53% radiochemical yields. In vitro experiments demonstrated high cellular uptake of 4-7-18FFTrps in different tumor cell lines. 4, 5-, and 6-18FFTrps, although stable in vitro, suffered from rapid in vivo defluorination. In contrast, 7-18FFTrp demonstrated a high in vivo stability and enabled a clear delineation of serotonergic areas and melatonin-producing pineal gland in rat brains. Moreover 7-18FFTrp accumulated in different tumor xenografts in a chick embryo CAM model. Thus, 7-18FFTrp represents a highly promising PET probe for imaging of Trp metabolism.