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01-02-2016 | Brief Article

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

Authors: 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

Published in: Molecular Imaging and Biology | Issue 1/2016

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.

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Edwards BK, Noone AM, Mariotto AB et al (2014) Annual Report to the Nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer 120:1290–1314PubMedCentralCrossRefPubMed

Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108CrossRefPubMed

Deppen S, Putnam JB Jr, Andrade G et al (2011) Accuracy of FDG-PET to diagnose lung cancer in a region of endemic granulomatous disease. Ann Thorac Surg 92:428–432, discussion 433 PubMedCentralCrossRefPubMed

Burger IA, Zitzmann-Kolbe S, Pruim J et al (2014) First clinical results of (D)-18F-Fluoromethyltyrosine (BAY 86-9596) PET/CT in patients with non-small cell lung cancer and head and neck squamous cell carcinoma. J Nucl Med 55:1778–1785CrossRefPubMed

Liu W, Le A, Hancock C et al (2012) Reprogramming of proline and glutamine metabolism contributes to the proliferative and metabolic responses regulated by oncogenic transcription factor c-MYC. Proc Natl Acad Sci U S A 109:8983–8988PubMedCentralCrossRefPubMed

Gaglio D, Metallo CM, Gameiro PA et al (2011) Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth. Mol Syst Biol 7:523PubMedCentralCrossRefPubMed

Wang JB, Erickson JW, Fuji R et al (2010) Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell 18:207–219PubMedCentralCrossRefPubMed

Brower M, Carney DN, Oie HK, Gazdar AF, Minna JD (1986) Growth of cell lines and clinical specimens of human non-small cell lung cancer in a serum-free defined medium. Cancer Res 46:798–806PubMed

Drogat B, Bouchecareilh M, North S et al (2007) Acute L-glutamine deprivation compromises VEGF-a upregulation in A549/8 human carcinoma cells. J Cell Physiol 212:463–472CrossRefPubMed

10.

Shelton LM, Huysentruyt LC, Seyfried TN (2010) Glutamine targeting inhibits systemic metastasis in the VM-M3 murine tumor model. Int J Cancer 127:2478–2485PubMedCentralCrossRefPubMed

11.

Hassanein M, Hoeksema MD, Shiota M et al (2013) SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival. Clin Cancer Res 19:560–570PubMedCentralCrossRefPubMed

12.

Hassanein M, Qian J, Hoeksema MD, et al (2015) Targeting SLC1A5-mediated glutamine dependence in non-small cell lung cancer. Int J Cancer. doi:10.1002/ijc.29535

13.

Qu W, Zha Z, Ploessl K et al (2011) Synthesis of optically pure 4-fluoro-glutamines as potential metabolic imaging agents for tumors. J Am Chem Soc 133:1122–1133CrossRefPubMed

14.

Regales L, Balak MN, Gong Y et al (2007) Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitors. PLoS One 2, e810PubMedCentralCrossRefPubMed

15.

Qu W, Oya S, Lieberman BP et al (2012) Preparation and characterization of L-[5-11C]-glutamine for metabolic imaging of tumors. J Nucl Med 53:98–105CrossRefPubMed

16.

Hight MR, Cheung YY, Nickels ML et al (2014) A peptide-based positron emission tomography probe for in vivo detection of caspase activity in apoptotic cells. Clin Cancer Res 20:2126–2135PubMedCentralCrossRefPubMed

17.

Chmielecki J, Foo J, Oxnard GR et al (2011) Optimization of dosing for EGFR-mutant non-small cell lung cancer with evolutionary cancer modeling. Sci Transl Med 3:90ra59PubMedCentralCrossRefPubMed

18.

Ohashi K, Maruvka YE, Michor F, Pao W (2013) Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease. J Clin Oncol 31:1070–1080PubMedCentralCrossRefPubMed

19.

Deppen SA, Blume JD, Kensinger CD et al (2014) Accuracy of FDG-PET to diagnose lung cancer in areas with infectious lung disease: a meta-analysis. JAMA 312:1227–1236PubMedCentralCrossRefPubMed

20.

Venneti S, Dunphy MP, Zhang H et al (2015) Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo. Sci Transl Med 7:274ra217CrossRef

21.

Schulte ML, Dawson ES, Saleh SA, Cuthbertson ML, Manning HC (2015) 2-Substituted Nγ-glutamylanilides as novel probes of ASCT2 with improved potency. Bioorg Med Chem Lett 25:113–116PubMedCentralCrossRefPubMed

22.

Wu Z, Zha Z, Li G, et al (2014) [(18)F](2S,4S)-4-(3-Fluoropropyl)glutamine as a tumor imaging agent. Mol Pharm 11(11):3852–3866

Title: Preclinical Evaluation of 4-[18F]Fluoroglutamine PET to Assess ASCT2 Expression in Lung Cancer
Authors: 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
Publication date: 01-02-2016
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 1/2016
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-015-0862-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Procedures

Result

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Result

Conclusions

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