H. Manning
Faculty Member
Last active: 3/22/2018

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

Hassanein M, Hight MR, Buck JR, Tantawy MN, Nickels ML, Hoeksema MD, Harris BK, Boyd K, Massion PP, Manning HC
Mol Imaging Biol. 2016 18 (1): 18-23

PMID: 25971659 · PMCID: PMC4644503 · DOI:10.1007/s11307-015-0862-4

PURPOSE - Alanine-serine-cysteine transporter 2 (ASCT2) expression has been demonstrated as a promising lung cancer biomarker. (2S,4R)-4-[(18)F]Fluoroglutamine (4-[(18)F]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-[(18)F]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-[(18)F]Fluoro-Gln uptake, but not 2-deoxy-2-[(18)F]fluoro-D-glucose, correlated with relative ASCT2 levels in xenograft tumors. In genetically engineered mice, 4-[(18)F]fluoro-Gln accumulation was significantly elevated in lung tumors, relative to normal lung and cardiac tissues.

CONCLUSIONS - 4-[(18)F]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.

MeSH Terms (16)

Amino Acid Transport System ASC Animals Carcinoma, Non-Small-Cell Lung Cell Line, Tumor Colonic Neoplasms ErbB Receptors Female Glutamine Humans Lung Neoplasms Male Mice, Nude Minor Histocompatibility Antigens Mutation Positron-Emission Tomography Xenograft Model Antitumor Assays

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