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Tryptophan-kynurenine pathway PET imaging in human gliomas.

Award Number: R01CA309136
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2031

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Tryptophan-kynurenine pathway PET imaging in human gliomas. - PROJECT SUMMARY Despite improved diagnosis and a few new therapeutic options, prognosis of patients with malignant glioma, particularly those with glioblastoma, remains dismal. Recent diagnostic imaging protocols in glioma patients started to incorporate amino acid PET imaging for improved glioma detection, but currently used amino acid analog tracers target only transporter activity and do not provide direct information on tumor-relevant metabolic activity. Upregulation of tumoral tryptophan metabolism via the immunosuppressive tryptophan-derived kynurenine pathway is an important mechanism of glioma immune tolerance, mediated by upregulated key enzymes of this pathway, which can be targeted by inhibitors to block tryptophan metabolism via this pathway. Our previous, proof-of-concept studies in glioma patients with a C-11 (short half-life) tryptophan analog PET radiotracer demonstrated the strong ability of such an imaging approach to detect glioma-infiltrated brain, differentiate post-treatment progression from radiation injury, and predict survival. In the current translational imaging project, we will translate a novel, clinically more feasible (F-18-labeled, longer half-life) PET radiotracer ([18F]fluoroethyl-L-tryptophan, [18F]FETrp) to clinical applications while using innovative multi-modal imaging methods complemented by cutting-edge analytic approaches to improve pre-and post-treatment evaluation and enhance targeted glioma treatments with the ultimate goal of improved survival. In Aim 1, we will evaluate the accuracy of PET-derived tryptophan kinetic parametric maps to detect pre- radiotherapy glioblastoma (IDH wild-type) extent including non-enhancing brain regions, whose incomplete treatment can lead to early post-treatment tumor progression and shorter survival. In Aim 2, we will determine the sensitivity and specificity of [18F]FETrp PET parametric maps (alone and/or in combination with advanced MRI) to differentiate post-radiation glioblastoma progression from radiation-induced MRI changes after the initial signs of MRI progression. In Aim 3, we will determine if pharmacologic inhibition of the kynurenine pathway, while using an FDA- approved drug, will reduce tumoral tryptophan metabolic rates as monitored by [18F]FETrp PET imaging. The expected results will (i) establish the clinical value of this highly feasible, quantitative PET imaging approach to improve targeted treatment and survival of pre- and post-treatment glioblastomas, and (ii) provide proof-of-concept data for a new imaging tool to monitor the effect of kynurenine pathway inhibition aiming to alleviate tumoral immune suppression mediated by the druggable tryptophan-kynurenine pathway.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $513,901 )
2026	2026	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Cancer Detection and Diagnosis Research	000	1	6/25/2026	NEW	$513,901
														Subtotal = $513,901

Grand Total All Awards = $513,901

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Tryptophan-kynurenine pathway PET imaging in human gliomas.

Award Number: R01CA309136

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2031

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