Abstract
Abnormal tryptophan metabolism via the kynurenine pathway is involved in the pathophysiology of a variety of human diseases including cancers. α-(11)C-methyl-l-tryptophan ((11)C-AMT) PET imaging demonstrated increased tryptophan uptake and trapping in epileptic foci and brain tumors, but the short half-life of (11)C limits its widespread clinical application. Recent in vitro studies suggested that the novel radiotracer 1-(2-(18)F-fluoroethyl)-l-tryptophan ((18)F-FETrp) may be useful to assess tryptophan metabolism via the kynurenine pathway. In this study, we tested in vivo organ and tumor uptake and kinetics of (18)F-FETrp in patient-derived xenograft mouse models and compared them with (11)C-AMT uptake. METHODS: Xenograft mouse models of glioblastoma and metastatic brain tumors (from lung and breast cancer) were developed by subcutaneous implantation of patient tumor fragments. Dynamic PET scans with (18)F-FETrp and (11)C-AMT were obtained for mice bearing human brain tumors 1-7 d apart. The biodistribution and tumoral SUVs for both tracers were compared. RESULTS: (18)F-FETrp showed prominent uptake in the pancreas and no bone uptake, whereas (11)C-AMT showed higher uptake in the kidneys. Both tracers showed uptake in the xenograft tumors, with a plateau of approximately 30 min after injection; however, (18)F-FETrp showed higher tumoral SUV than (11)C-AMT in all 3 tumor types tested. The radiation dosimetry for (18)F-FETrp determined from the mouse data compared favorably with the clinical (18)F-FDG PET tracer. CONCLUSION: (18)F-FETrp tumoral uptake, biodistribution, and radiation dosimetry data provide strong preclinical evidence that this new radiotracer warrants further studies that may lead to a broadly applicable molecular imaging tool to examine abnormal tryptophan metabolism in human tumors.