Preclinical Evaluation of 4-[18F]Fluoroglutamine PET to Assess ASCT2 Expression in Lung Cancer

Mohamed Hassanein; Matthew R. Hight; Jason R. Buck; Mohammed N. Tantawy; Michael L. Nickels; Megan D. Hoeksema; Bradford K. Harris; Kelli Boyd; Pierre P. Massion; H. Charles Manning

doi:10.1007/s11307-015-0862-4

Preclinical Evaluation of 4-[¹⁸F]Fluoroglutamine PET to Assess ASCT2 Expression in Lung Cancer

Mohamed Hassanein, Matthew R. Hight, Jason R. Buck, Mohammed N. Tantawy, Michael L. Nickels, Megan D. Hoeksema, Bradford K. Harris, Kelli Boyd, Pierre P. Massion, H. Charles Manning

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

41 Scopus citations

Abstract

Purpose: Alanine-serine-cysteine transporter 2 (ASCT2) expression has been demonstrated as a promising lung cancer biomarker. (2S,4R)-4-[¹⁸F]Fluoroglutamine (4-[¹⁸F]fluoro-Gln) positron emission tomography (PET) was evaluated in preclinical models of non-small cell lung cancer as a quantitative, non-invasive measure of ASCT2 expression. Procedures: In vivo microPET studies of 4-[¹⁸F]fluoro-Gln uptake were undertaken in human cell line xenograft tumor-bearing mice of varying ASCT2 levels, followed by a genetically engineered mouse model of epidermal growth factor receptor (EGFR)-mutant lung cancer. The relationship between a tracer accumulation and ASCT2 levels in tumors was evaluated by IHC and immunoblotting. Result: 4-[¹⁸F]Fluoro-Gln uptake, but not 2-deoxy-2-[¹⁸F]fluoro-D-glucose, correlated with relative ASCT2 levels in xenograft tumors. In genetically engineered mice, 4-[¹⁸F]fluoro-Gln accumulation was significantly elevated in lung tumors, relative to normal lung and cardiac tissues. Conclusions: 4-[¹⁸F]Fluoro-Gln PET appears to provide a non-invasive measure of ASCT2 expression. Given the potential of ASCT2 as a lung cancer biomarker, this and other tracers reflecting ASCT2 levels could emerge as precision imaging diagnostics in this setting.

Original language	English (US)
Pages (from-to)	18-23
Number of pages	6
Journal	Molecular Imaging and Biology
Volume	18
Issue number	1
DOIs	https://doi.org/10.1007/s11307-015-0862-4
State	Published - Feb 1 2016
Externally published	Yes

Keywords

ASCT2
Cancer
Glutamine
Lung
NSCLC
PET
SCC
SLC1A5
Transporter

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

Access to Document

10.1007/s11307-015-0862-4

Cite this

@article{7ffea7c25da74cbc81b28cbab4aa0d79,

title = "Preclinical Evaluation of 4-[18F]Fluoroglutamine PET to Assess ASCT2 Expression in Lung Cancer",

abstract = "Purpose: Alanine-serine-cysteine transporter 2 (ASCT2) expression has been demonstrated as a promising lung cancer biomarker. (2S,4R)-4-[18F]Fluoroglutamine (4-[18F]fluoro-Gln) positron emission tomography (PET) was evaluated in preclinical models of non-small cell lung cancer as a quantitative, non-invasive measure of ASCT2 expression. Procedures: In vivo microPET studies of 4-[18F]fluoro-Gln uptake were undertaken in human cell line xenograft tumor-bearing mice of varying ASCT2 levels, followed by a genetically engineered mouse model of epidermal growth factor receptor (EGFR)-mutant lung cancer. The relationship between a tracer accumulation and ASCT2 levels in tumors was evaluated by IHC and immunoblotting. Result: 4-[18F]Fluoro-Gln uptake, but not 2-deoxy-2-[18F]fluoro-D-glucose, correlated with relative ASCT2 levels in xenograft tumors. In genetically engineered mice, 4-[18F]fluoro-Gln accumulation was significantly elevated in lung tumors, relative to normal lung and cardiac tissues. Conclusions: 4-[18F]Fluoro-Gln PET appears to provide a non-invasive measure of ASCT2 expression. Given the potential of ASCT2 as a lung cancer biomarker, this and other tracers reflecting ASCT2 levels could emerge as precision imaging diagnostics in this setting.",

keywords = "ASCT2, Cancer, Glutamine, Lung, NSCLC, PET, SCC, SLC1A5, Transporter",

author = "Mohamed Hassanein and Hight, {Matthew R.} and Buck, {Jason R.} and Tantawy, {Mohammed N.} and Nickels, {Michael L.} and Hoeksema, {Megan D.} and Harris, {Bradford K.} and Kelli Boyd and Massion, {Pierre P.} and Manning, {H. Charles}",

note = "Funding Information: This work was supported by the Lung Cancer Research Foundation (LCRF), Vanderbilt Center for Molecular Probes (VCMP), NIH (ICMIC P50-CA128323, 2RO1CA102353, U01CA152662, P50-CA090949, P50-CA128323, P30-DK058404), and Kleberg Foundation. Publisher Copyright: {\textcopyright} 2015, World Molecular Imaging Society.",

year = "2016",

month = feb,

day = "1",

doi = "10.1007/s11307-015-0862-4",

language = "English (US)",

volume = "18",

pages = "18--23",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer New York",

number = "1",

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TY - JOUR

T1 - Preclinical Evaluation of 4-[18F]Fluoroglutamine PET to Assess ASCT2 Expression in Lung Cancer

AU - Hassanein, Mohamed

AU - Hight, Matthew R.

AU - Buck, Jason R.

AU - Tantawy, Mohammed N.

AU - Nickels, Michael L.

AU - Hoeksema, Megan D.

AU - Harris, Bradford K.

AU - Boyd, Kelli

AU - Massion, Pierre P.

AU - Manning, H. Charles

N1 - Funding Information: This work was supported by the Lung Cancer Research Foundation (LCRF), Vanderbilt Center for Molecular Probes (VCMP), NIH (ICMIC P50-CA128323, 2RO1CA102353, U01CA152662, P50-CA090949, P50-CA128323, P30-DK058404), and Kleberg Foundation. Publisher Copyright: © 2015, World Molecular Imaging Society.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Purpose: Alanine-serine-cysteine transporter 2 (ASCT2) expression has been demonstrated as a promising lung cancer biomarker. (2S,4R)-4-[18F]Fluoroglutamine (4-[18F]fluoro-Gln) positron emission tomography (PET) was evaluated in preclinical models of non-small cell lung cancer as a quantitative, non-invasive measure of ASCT2 expression. Procedures: In vivo microPET studies of 4-[18F]fluoro-Gln uptake were undertaken in human cell line xenograft tumor-bearing mice of varying ASCT2 levels, followed by a genetically engineered mouse model of epidermal growth factor receptor (EGFR)-mutant lung cancer. The relationship between a tracer accumulation and ASCT2 levels in tumors was evaluated by IHC and immunoblotting. Result: 4-[18F]Fluoro-Gln uptake, but not 2-deoxy-2-[18F]fluoro-D-glucose, correlated with relative ASCT2 levels in xenograft tumors. In genetically engineered mice, 4-[18F]fluoro-Gln accumulation was significantly elevated in lung tumors, relative to normal lung and cardiac tissues. Conclusions: 4-[18F]Fluoro-Gln PET appears to provide a non-invasive measure of ASCT2 expression. Given the potential of ASCT2 as a lung cancer biomarker, this and other tracers reflecting ASCT2 levels could emerge as precision imaging diagnostics in this setting.

AB - Purpose: Alanine-serine-cysteine transporter 2 (ASCT2) expression has been demonstrated as a promising lung cancer biomarker. (2S,4R)-4-[18F]Fluoroglutamine (4-[18F]fluoro-Gln) positron emission tomography (PET) was evaluated in preclinical models of non-small cell lung cancer as a quantitative, non-invasive measure of ASCT2 expression. Procedures: In vivo microPET studies of 4-[18F]fluoro-Gln uptake were undertaken in human cell line xenograft tumor-bearing mice of varying ASCT2 levels, followed by a genetically engineered mouse model of epidermal growth factor receptor (EGFR)-mutant lung cancer. The relationship between a tracer accumulation and ASCT2 levels in tumors was evaluated by IHC and immunoblotting. Result: 4-[18F]Fluoro-Gln uptake, but not 2-deoxy-2-[18F]fluoro-D-glucose, correlated with relative ASCT2 levels in xenograft tumors. In genetically engineered mice, 4-[18F]fluoro-Gln accumulation was significantly elevated in lung tumors, relative to normal lung and cardiac tissues. Conclusions: 4-[18F]Fluoro-Gln PET appears to provide a non-invasive measure of ASCT2 expression. Given the potential of ASCT2 as a lung cancer biomarker, this and other tracers reflecting ASCT2 levels could emerge as precision imaging diagnostics in this setting.

KW - ASCT2

KW - Cancer

KW - Glutamine

KW - Lung

KW - NSCLC

KW - PET

KW - SCC

KW - SLC1A5

KW - Transporter

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U2 - 10.1007/s11307-015-0862-4

DO - 10.1007/s11307-015-0862-4

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