Correlation between positron emission tomography findings and glucose transporter 1, 3 and L‑type amino acid transporter 1 mRNA expression in primary central nervous system lymphomas

Takahashi,Yoshinobu; Akahane,Toshiaki; Yamamoto,Daisuke; Nakamura,Hideo; Sawa,Hiroki; Nitta,Kazumi; Ide,Wataru; Hashimoto,Ikuo; Kamada,Hajime

doi:10.3892/mco.2014.287

Correlation between positron emission tomography findings and glucose transporter 1, 3 and L‑type amino acid transporter 1 mRNA expression in primary central nervous system lymphomas

Authors:
- Yoshinobu Takahashi
- Toshiaki Akahane
- Daisuke Yamamoto
- Hideo Nakamura
- Hiroki Sawa
- Kazumi Nitta
- Wataru Ide
- Ikuo Hashimoto
- Hajime Kamada
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Affiliations: Department of Neurosurgery, Hokuto Hospital, Obihiro, Hokkaido 080‑0039, Japan, Oncology Research Center, Hokuto Hospital, Obihiro, Hokkaido 080‑0039, Japan, Department of Radiology, Hokuto Hospital, Obihiro, Hokkaido 080‑0039, Japan, Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860‑8556, Japan
Published online on: May 5, 2014 https://doi.org/10.3892/mco.2014.287
Pages: 525-529

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Abstract

Primary central nervous system lymphoma (PCNSL) is an aggressive form of non‑Hodgkin lymphoma with a poor prognosis. [18F] 2‑fluoro‑2‑deoxy‑d‑glucose (FDG) and l‑(methyl‑11C)‑methionine (MET) are the most widely used tracers in oncological positron emission tomography studies for PCNSL and commonly identify hypermetabolic lesions through increased uptake of FDG and MET. However, the mechanisms underlying the uptake of FDG and MET in PCNSL have not been clearly determined. The present study aimed to investigate the mRNA expression levels of glucose transporter (GLUT)1, GLUT3 and L‑type amino acid transporter 1 (LAT1) in resected PCNSL specimens, in order to identify whether these transporters are associated with the increased uptake of FDG and MET. A total of 7 patients diagnosed with PCNSL were investigated. The uptake of FDG and MET by the tumors was evaluated based on the maximum standardized uptake value (SUVmax). The quantity of GLUT1, GLUT3 and LAT1 mRNA in the PCNSL specimens was measured to determine whether GLUT1, GLUT3 and̸or LAT1 are involved in the increased uptake of FDG and MET in PCNSL. Furthermore, microvessel density (MVD) and cell density (CD) were measured in all the cases. Our results indicated that the expression of GLUT3, but not GLUT1, was significantly correlated with FDG SUVmax and the expression of LAT1 was significantly correlated with MET SUVmax. However, neither MVD nor CD were found to be significantly associated with the uptake of FDG and MET. GLUT3 was identified as a key determinant of FDG accumulation, whereas LAT1 was a key determinant of MET accumulation in PCNSL. Therefore, GLUT3 and LAT1 may represent potential targets for the future development of novel therapeutic agents for PCNSL.

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1	Corn BW, Marcus SM, Topham A, Hauck W and Curran WJ Jr: Will primary central nervous system lymphoma be the most frequent brain tumor diagnosed in the year 2000? Cancer. 79:2409–2413. 1997.
2	Kawai N, Nishiyama Y, Miyake K, Tamiya T and Nagao S: Evaluation of tumor FDG transport and metabolism in primary central nervous system lymphoma using [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) kinetic analysis. Ann Nucl Med. 19:685–690. 2005.PubMed/NCBI
3	Nishiyama Y, Yamamoto Y, Monden T, Sasakawa Y, Kawai N, Satoh K and Ohkawa M: Diagnostic value of kinetic analysis using dynamic FDG PET in immunocompetent patients with primary CNS lymphoma. Eur J Nucl Med Mol Imaging. 34:78–86. 2007. View Article : Google Scholar : PubMed/NCBI
4	Ogawa T, Kanno I, Hatazawa J, et al: Methionine PET for follow-up of radiation therapy of primary lymphoma of the brain. Radiographics. 14:101–110. 1994. View Article : Google Scholar : PubMed/NCBI
5	Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956. View Article : Google Scholar : PubMed/NCBI
6	Reske SN, Grillenberger KG, Glatting G, Port M, Hildebrandt M, Gansauge F and Beger HG: Overexpression of glucose transporter 1 and increased FDG uptake in pancreatic carcinoma. J Nucl Med. 38:1344–1348. 1997.PubMed/NCBI
7	Brown RS and Wahl RL: Overexpression of Glut-1 glucose transporter in human breast cancer. An immunohistochemical study. Cancer. 72:2979–2985. 1993. View Article : Google Scholar : PubMed/NCBI
8	Younes M, Brown RW, Stephenson M, Gondo M and Cagle PT: Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival. Cancer. 80:1046–1051. 1997. View Article : Google Scholar : PubMed/NCBI
9	Suzuki T, Iwazaki A, Katagiri H, Oka Y, Redpath JL, Stanbridge EJ and Kitagawa T: Enhanced expression of glucose transporter GLUT3 in tumorigenic HeLa cell hybrids associated with tumor suppressor dysfunction. Eur J Biochem. 262:534–540. 1999. View Article : Google Scholar : PubMed/NCBI
10	Kaira K, Oriuchi N, Shimizu K, Imai H, Tominaga H, Yanagitani N, Sunaga N, Hisada T, Ishizuka T, Kanai Y, et al: Comparison of L-type amino acid transporter 1 expression and L-[3–¹⁸F]-α-methyl tyrosine uptake in outcome of non-small cell lung cancer. Nucl Med Biol. 37:911–916. 2010.
11	Sakata T, Ferdous G, Tsuruta T, Satoh T, Baba S, Muto T, Ueno A, Kanai Y, Endou H and Okayasu I: L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer. Pathol Int. 59:7–18. 2009. View Article : Google Scholar : PubMed/NCBI
12	Zhen HN, Zhang X, Hu PZ, Yang TT, Fei Z, Zhang JN, Fu LA, He XS, Ma FC and Wang XL: Surviving expression and its relation with proliferation, apoptosis, and angiogenesis in brain gliomas. Cancer. 104:2775–2783. 2005. View Article : Google Scholar : PubMed/NCBI
13	Ganapathy V, Thangaraju M and Prasad PD: Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Ther. 121:29–40. 2009. View Article : Google Scholar : PubMed/NCBI
14	Uldry M and Thorens B: The SLC2 family of facilitated hexose and polyol transporters. Pflugers Arch. 447:480–489. 2004. View Article : Google Scholar : PubMed/NCBI
15	Watanabe Y, Suefuji H, Hirose Y, et al: ¹⁸F-FDG uptake in primary gastric malignant lymphoma correlates with glucose transporter 1 expression and histologic malignant potential. Int J Hematol. 97:43–49. 2013. View Article : Google Scholar
16	Khandani AH, Dunphy CH, Meteesatien P, Dufault DL, Ivanovic M and Shea TC: Glut1 and Glut3 expression in lymphoma and their association with tumor intensity on ¹⁸F-fluorodeoxyglucose positron emission tomography. Nucl Med Commun. 30:594–601. 2009. View Article : Google Scholar : PubMed/NCBI
17	Palmedo H, Urbach H, Bender H, Schlegel U, Schmidt-Wolf IG, Matthies A, Linnebank M, Joe A, Bucerius J, Biersack HJ and Pels H: FDG-PET in immunocompetent patients with primary central nervous system lymphoma: correlation with MRI and clinical follow-up. Eur J Nucl Med Mol Imaging. 33:164–168. 2006. View Article : Google Scholar : PubMed/NCBI
18	Glass J, Gluber ML, Cher L and Hochberg FH: Preirradiation methotrexate chemotherapy of primary central nervous system lymphoma: long-term outcome. J Neurosurg. 81:188–195. 1994. View Article : Google Scholar : PubMed/NCBI
19	Abrey LE, DeAngelis LM and Yahalom J: Long-term survival in primary CNS lymphoma. J Clin Oncol. 16:859–863. 1998.PubMed/NCBI
20	Kawai N, Zhen HN, Miyake K, Yamamaoto Y, Nishiyama Y and Tamiya T: Prognostic value of pretreatment 18F-FDG PET in patients with primary central nervous system lymphoma: SUV-based assessment. J Neurooncol. 100:225–232. 2010. View Article : Google Scholar : PubMed/NCBI
21	Kanai Y, Segawa H, Miyamoto Ki, Uchino H, Takeda E and Endou H: Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J Biol Chem. 273:23629–23632. 1998. View Article : Google Scholar : PubMed/NCBI
22	Okubo S, Zhen HN, Kawai N, Nishiyama Y, Haba R and Tamiya T: Correlation of L-methyl-¹¹C-methionine (MET) uptake with L-type amino acid transporter 1 in human gliomas. J Neurooncol. 99:217–225. 2010.
23	Nojiri T, Nariai T, Aoyagi M, Senda M, Ishii K, Ishiwata K and Ohno K: Contributions of biological tumor parameters to the incorporation rate of L-[methyl-¹¹C] methionine into astrocytomas and oligodendrogliomas. J Neurooncol. 93:233–241. 2009.
24	Kracht LW, Friese M, Herholz K, Schroeder R, Bauer B, Jacobs A and Heiss WD: Methyl-[¹¹C]-l-methionine uptake as measured by positron emission tomography correlates to microvessel density in patients with glioma. Eur J Nucl Med Mol Imaging. 30:868–873. 2003.
25	Okita Y, Kinoshita M, Goto T, Kagawa N, Kishima H, Shimosegawa E, Hatazawa J, Hashimoto N and Yoshimine T: ¹¹C-methionine uptake correlates with tumor cell density rather than with microvessel density in glioma: A stereotactic image-histology comparison. Neuroimage. 49:2977–2982. 2010. View Article : Google Scholar