Assessment of Tryptophan Uptake and Kinetics Using 1-(2-18f-fluoroethyl)-l-tryptophan and Α-11C-methyl-l-tryptophan PET Imaging in Mice Implanted with Patient-Derived Brain Tumor Xenografts

Abnormal tryptophan metabolism via the kynurenine pathway is involved in the pathophysiology of a variety of human diseases including cancers. alpha-C-11-methyl-L-tryptophan (C-11-AMT) PET imaging demonstrated increased tryptophan uptake and trapping in epileptic foci and brain tumors, but the short half-life of C-11 limits its widespread clinical application. Recent in vitro studies suggested that the novel radiotracer 1-(2-F-18-fluoroethyl)-L-tryptophan (F-18-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 F-18-FETrp in patient-derived xenograft mouse models and compared them with C-11-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 F-18-FETrp and C-11-AMT were obtained for mice bearing human brain tumors 1-7 d apart. The biodistribution and tumoral SUVs for both tracers were compared. Results: F-18-FETrp showed prominent uptake in the pancreas and no bone uptake, whereas C-11-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, F-18-FETrp showed higher tumoral SUV than C-11-AMT in all 3 tumor types tested. The radiation dosimetry for F-18-FETrp determined from the mouse data compared favorably with the clinical F-18-FDG PET tracer. Conclusion: F-18-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.