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

Sriram Venneti; Mark P. Dunphy; Hanwen Zhang; Kenneth L. Pitter; Patrick Zanzonico; Carl Campos; Sean D. Carlin; Gaspare La Rocca; Serge Lyashchenko; Karl Ploessl; Daniel Rohle; Antonio M. Omuro; Justin R. Cross; Cameron W. Brennan; Wolfgang A. Weber; Eric C. Holland; Ingo K. Mellinghoff; Hank F. Kung; Jason S. Lewis; Craig B. Thompson

doi:10.1126/scitranslmed.aaa1009

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

Sriram Venneti, Mark P. Dunphy, Hanwen Zhang, Kenneth L. Pitter, Patrick Zanzonico, Carl Campos, Sean D. Carlin, Gaspare La Rocca, Serge Lyashchenko, Karl Ploessl, Daniel Rohle, Antonio M. Omuro, Justin R. Cross, Cameron W. Brennan, Wolfgang A. Weber, Eric C. Holland, Ingo K. Mellinghoff, Hank F. Kung, Jason S. Lewis, Craig B. Thompson

Research output: Contribution to journal › Article › peer-review

248 Scopus citations

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 ¹⁸F-fluorodeoxyglucose (18F-FDG). However, ¹⁸F-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 4-18F-(2S,4R)-fluoroglutamine (18F-FGln) shows high uptake in gliomas but low background brain uptake, facilitating clear tumor delineation. Chemo/radiation therapy reduced 18F-FGln tumor avidity, corresponding with decreased tumor burden. ¹⁸F-FGln uptake was not observed in animals with a permeable blood-brain barrier or neuroinflammation. We translated these findings to human subjects, where ¹⁸F-FGln showed high tumor/background ratios with minimal uptake in the surrounding brain in human glioma patients with progressive disease. These data suggest that 18F-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.

Original language	English
Journal	Science translational medicine
Volume	7
Issue number	274
DOIs	https://doi.org/10.1126/scitranslmed.aaa1009
State	Published - Feb 11 2015

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Venneti, S., Dunphy, M. P., Zhang, H., Pitter, K. L., Zanzonico, P., Campos, C., Carlin, S. D., La Rocca, G., Lyashchenko, S., Ploessl, K., Rohle, D., Omuro, A. M., Cross, J. R., Brennan, C. W., Weber, W. A., Holland, E. C., Mellinghoff, I. K., Kung, H. F., Lewis, J. S., & Thompson, C. B. (2015). Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo. Science translational medicine, 7(274). https://doi.org/10.1126/scitranslmed.aaa1009

@article{6574a37e5562498eae2bc74ec4458844,

title = "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 18F-fluorodeoxyglucose (18F-FDG). However, 18F-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 4-18F-(2S,4R)-fluoroglutamine (18F-FGln) shows high uptake in gliomas but low background brain uptake, facilitating clear tumor delineation. Chemo/radiation therapy reduced 18F-FGln tumor avidity, corresponding with decreased tumor burden. 18F-FGln uptake was not observed in animals with a permeable blood-brain barrier or neuroinflammation. We translated these findings to human subjects, where 18F-FGln showed high tumor/background ratios with minimal uptake in the surrounding brain in human glioma patients with progressive disease. These data suggest that 18F-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.",

author = "Sriram Venneti and Dunphy, {Mark P.} and Hanwen Zhang and Pitter, {Kenneth L.} and Patrick Zanzonico and Carl Campos and Carlin, {Sean D.} and {La Rocca}, Gaspare and Serge Lyashchenko and Karl Ploessl and Daniel Rohle and Omuro, {Antonio M.} and Cross, {Justin R.} and Brennan, {Cameron W.} and Weber, {Wolfgang A.} and Holland, {Eric C.} and Mellinghoff, {Ingo K.} and Kung, {Hank F.} and Lewis, {Jason S.} and Thompson, {Craig B.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2015 by the American Association for the Advancement of Science.",

year = "2015",

month = feb,

day = "11",

doi = "10.1126/scitranslmed.aaa1009",

language = "English",

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Venneti, S, Dunphy, MP, Zhang, H, Pitter, KL, Zanzonico, P, Campos, C, Carlin, SD, La Rocca, G, Lyashchenko, S, Ploessl, K, Rohle, D, Omuro, AM, Cross, JR, Brennan, CW, Weber, WA, Holland, EC, Mellinghoff, IK, Kung, HF, Lewis, JS & Thompson, CB 2015, 'Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo', Science translational medicine, vol. 7, no. 274. https://doi.org/10.1126/scitranslmed.aaa1009

TY - JOUR

T1 - Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo

AU - Venneti, Sriram

AU - Dunphy, Mark P.

AU - Zhang, Hanwen

AU - Pitter, Kenneth L.

AU - Zanzonico, Patrick

AU - Campos, Carl

AU - Carlin, Sean D.

AU - La Rocca, Gaspare

AU - Lyashchenko, Serge

AU - Ploessl, Karl

AU - Rohle, Daniel

AU - Omuro, Antonio M.

AU - Cross, Justin R.

AU - Brennan, Cameron W.

AU - Weber, Wolfgang A.

AU - Holland, Eric C.

AU - Mellinghoff, Ingo K.

AU - Kung, Hank F.

AU - Lewis, Jason S.

AU - Thompson, Craig B.

PY - 2015/2/11

Y1 - 2015/2/11

N2 - 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 18F-fluorodeoxyglucose (18F-FDG). However, 18F-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 4-18F-(2S,4R)-fluoroglutamine (18F-FGln) shows high uptake in gliomas but low background brain uptake, facilitating clear tumor delineation. Chemo/radiation therapy reduced 18F-FGln tumor avidity, corresponding with decreased tumor burden. 18F-FGln uptake was not observed in animals with a permeable blood-brain barrier or neuroinflammation. We translated these findings to human subjects, where 18F-FGln showed high tumor/background ratios with minimal uptake in the surrounding brain in human glioma patients with progressive disease. These data suggest that 18F-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.

AB - 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 18F-fluorodeoxyglucose (18F-FDG). However, 18F-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 4-18F-(2S,4R)-fluoroglutamine (18F-FGln) shows high uptake in gliomas but low background brain uptake, facilitating clear tumor delineation. Chemo/radiation therapy reduced 18F-FGln tumor avidity, corresponding with decreased tumor burden. 18F-FGln uptake was not observed in animals with a permeable blood-brain barrier or neuroinflammation. We translated these findings to human subjects, where 18F-FGln showed high tumor/background ratios with minimal uptake in the surrounding brain in human glioma patients with progressive disease. These data suggest that 18F-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.

UR - http://www.scopus.com/inward/record.url?scp=84926661140&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.aaa1009

DO - 10.1126/scitranslmed.aaa1009

M3 - Article

C2 - 25673762

AN - SCOPUS:84926661140

SN - 1946-6234

VL - 7

JO - Science translational medicine

JF - Science translational medicine

IS - 274

ER -

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

Abstract

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