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Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo.

ABSTRACT: Glucose and glutamine are the two principal nutrients that cancer cells use to proliferate and survive. Many cancers show altered glucose metabolism, which constitutes the basis for in vivo positron emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)F-FDG). However, (18)F-FDG is ineffective in evaluating gliomas because of high background uptake in the brain. Glutamine metabolism is also altered in many cancers, and we demonstrate that PET imaging in vivo with the glutamine analog 4-(18)F-(2S,4R)-fluoroglutamine ((18)F-FGln) shows high uptake in gliomas but low background brain uptake, facilitating clear tumor delineation. Chemo/radiation therapy reduced (18)F-FGln tumor avidity, corresponding with decreased tumor burden. (18)F-FGln uptake was not observed in animals with a permeable blood-brain barrier or neuroinflammation. We translated these findings to human subjects, where (18)F-FGln showed high tumor/background ratios with minimal uptake in the surrounding brain in human glioma patients with progressive disease. These data suggest that (18)F-FGln is avidly taken up by gliomas, can be used to assess metabolic nutrient uptake in gliomas in vivo, and may serve as a valuable tool in the clinical management of gliomas.

SUBMITTER: Venneti S

PROVIDER: S-EPMC4431550 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo.

Venneti Sriram S Dunphy Mark P MP Zhang Hanwen H Pitter Kenneth L KL Zanzonico Patrick P Campos Carl C Carlin Sean D SD La Rocca Gaspare G Lyashchenko Serge S Ploessl Karl K Rohle Daniel D Omuro Antonio M AM Cross Justin R JR Brennan Cameron W CW Weber Wolfgang A WA Holland Eric C EC Mellinghoff Ingo K IK Kung Hank F HF Lewis Jason S JS Thompson Craig B CB

Science translational medicine 20150201 274

Glucose and glutamine are the two principal nutrients that cancer cells use to proliferate and survive. Many cancers show altered glucose metabolism, which constitutes the basis for in vivo positron emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)F-FDG). However, (18)F-FDG is ineffective in evaluating gliomas because of high background uptake in the brain. Glutamine metabolism is also altered in many cancers, and we demonstrate that PET imaging in vivo with the glutamine ana ...[more]

PMID: 25673762

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Project description:PURPOSE:Glioma treatment planning requires precise tumor delineation, which is typically performed with contrast-enhanced (CE) MRI. However, CE MRI fails to reflect the entire extent of glioma. O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET may detect tumor volumes missed by CE MRI. We investigated the clinical value of simultaneous FET-PET and CE MRI in delineating tumor extent before treatment planning. Guided stereotactic biopsy was used to validate the findings. METHODS:Conventional MRI and 18F-FET PET were performed simultaneously on a hybrid PET/MR in 33 patients with histopathologically confirmed glioma. Tumor volumes were quantified using a tumor-to-brain ratio???1.6 (VPET) and a visual threshold (VCE). We visually assessed abnormal areas on FLAIR images and calculated Dice's coefficient (DSC), overlap volume (OV), discrepancy-PET, and discrepancy-CE. Additionally, several stereotactic biopsy samples were taken from "matched" or "mismatched" FET-PET and CE MRI regions. RESULTS:Among 31 patients (93.94%), FET-PET delineated significantly larger tumor volumes than CE MRI (77.84?±?51.74 cm3 vs. 34.59?±?27.07 cm3, P?<?0.05). Of the 21 biopsy samples obtained from regions with increased FET uptake, all were histopathologically confirmed as glioma tissue or tumor infiltration, whereas only 13 showed enhancement on CE MRI. Among all patients, the spatial similarity between VPET and VCE was low (average DSC 0.56?±?0.22), while the overlap was high (average OV 0.95?±?0.08). The discrepancy-CE and discrepancy-PET were lower than 10% in 28 and 0 patients, respectively. Eleven patients showed VPET partially beyond abnormal signal areas on FLAIR images. CONCLUSION:The metabolically active biodistribution of gliomas delineated with FET-PET significantly exceeds tumor volume on CE MRI, and histopathology confirms these findings. Our preliminary results indicate that combining the anatomic and molecular information obtained from conventional MRI and FET-PET would reveal a more accurate glioma extent, which is critical for individualized treatment planning.

Dataset Information

Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo.

Publications

Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo.

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