RADI-17. EVALUATION OF A NOVEL 18F-LABELED TRYPTOPHAN TRACER FOR PET IMAGING OF BRAIN TUMORS IN A MEDULLOBLASTOMA MOUSE MODEL

Medulloblastoma is the most common malignant brain tumor of childhood. Despite major advances, long-term survival is hindered by relapse and leptomeningeal spread, necessitating the development of novel diagnostic and therapeutic approaches. Abnormal tryptophan metabolism, via the immunomodulatory indoleamine-2,3-dioxygenase (IDO)/ tryptophan-2,3 dioxygenase (TDO)-mediated kynurenine pathway (KP), has been demonstrated in tumors, and is emerging as a valid target for immunotherapy as well as non-invasive tumor imaging. Previously, a positron emission tomography (PET) tracer, α-[(11)C] methyl-L-tryptophan ([(11)C] AMT), has been successfully used to evaluate the increased tryptophan metabolism and uptake through KP in patients with glioma. Nevertheless, the short half-life of the carbon-11 isotope has limited the broad applications of [(11)C] AMT in clinical research and diagnostics. In this study, using a novel PET tracer, 1-(2-[(18)F]fluoroethyl)-L-tryptophan (L-1-[(18)F]FETrp) with similar pathophysiological and metabolic properties as [(11)C] AMT, we assessed the tryptophan metabolism in a transgenic mouse model of the Sonic hedgehog (Shh) subgroup of medulloblastoma. In Smo-Smo mice, preliminary PET imaging data showed increased accumulation of L-1-[(18)F]FETrp in tumors as compared to normal brain tissue. Immunofluorescence and molecular analysis of tumor tissues obtained from Smo-Smo mice indicated increased expression of TDO2, but not IDO1. Both TDO2 and IDO1 are tissue-specific first step and rate-limiting enzymes of the KP of tryptophan metabolism. Thus, our preclinical studies in Smo-Smo mice indicate that L-1-[(18)F]FETrp may be a suitable tracer for PET imaging of medulloblastoma tumors and could provide valuable information for noninvasive assessment of immunotherapy response and move towards targeted therapy for medulloblastoma in the future.