BACKGROUND: Recently the kynurenine pathway (KP), which is responsible for ∼99% of the catabolism of the amino acid tryptophan (TRP), has been implicated in the pathophysiology of human gliomas. Furthermore, studies indicate that the KP plays a role in local anti-tumor immune suppression both directly and indirectly by depleting TRP and causing T-cell cell cycle arrest. The KP can be studied through the use of a non-invasive molecular imaging tracer, α-[11C]-methyl-L-tryptophan (AMT). AMT-PET can predict survival in GBM patients with recurrent disease (Kamson et al., Neuro-Oncology, 2014). METHODS: In order to study the KP, we generated patient-derived xenograft (PDX) models of five GBMs. One cell line, KCI-GBM-1040, was implanted intracranially and AMT scans were obtained 9 and 14 days post-op. In vivo analysis of the tumors was performed via immunohistochemistry (IHC) and AMT-PET scans. Formalin fixed tissue sections were stained with antibodies specific for human indoleamine 2,3-dioxygenase (IDO) 1, IDO2, tryptophan 2,3-dioxygenase (TDO2), kynureninase (KYNU), kynurenine 3-monooxygenase (KMO), and the large amino acid transporter, LAT1, which is responsible for the uptake of TRP and AMT. RESULTS: Micro-PET imaging showed robust tumoral AMT uptake in PDX mice with prolonged tracer accumulation over a 60-min scan, with average uptake increasing 38% between 10 minutes and the maximum at 50 minutes. This is consistent with AMT trapping seen in human gliomas. Tumor tissues from both the patient and xenografts showed similar immunostaining results for both the TRP-converting and the downstream enzymes of the KP. CONCLUSIONS: These preliminary results indicate that our PDX model is representative of the human disease as it relates to both the in vitro and in vivo study of the KP. These models allow us to study the KP and offer a novel system through which we can develop and test new therapies for GBM patients.