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[18F]3′-deoxy-3′-fluorothymidine PET for the diagnosis and grading of brain tumors

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Abstract

Abstract

The aim of this study was to evaluate the feasibility of using [18F] 3′-deoxy-3′-fluorothymidine (FLT) positron emission tomography (PET) for the diagnosis and grading of brain tumors.

Methods

The patient population comprised 26 patients (15 males, 11 females) with brain tumors (n=18) or nontumorous lesions (n=8). 2-[18F]fluoro-2-deoxy-d-glucose (FDG) and FLT PET images were obtained using a dedicated PET scanner 1 h after the injection of 370 MBq of FDG or FLT. Uptake of FDG and FLT by the lesions was visually and semiquantitatively assessed in comparison with normal brain tissue.

Results

Of 26 brain lesions, four showed increased FDG uptake compared with normal gray matter (grade 5). These four lesions showed intensely increased FLT uptake and were all high-grade tumors. Twenty-two lesions with similar (grade 4) or decreased (grades 1–3) FDG uptake compared with normal gray matter showed variable pathology. Among the 18 brain tumors, FLT PET showed increased uptake in all 12 high-grade tumors but FDG uptake was variable. In 22 brain lesions with similar or decreased uptake compared with normal gray matter on FDG PET, the sensitivity and specificity of FLT PET for the diagnosis of brain tumor were 79% (11/14) and 63% (5/8), respectively. The uptake ratios of 14 brain tumors on FLT PET were significantly higher than the lesion to gray matter ratios (p=0.012) and lesion to white matter ratios (p=0.036) of FDG uptake and differed significantly between high (5.1±2.6) and low (2.1±1.1) grade tumors (p=0.029). In nine gliomas, FLT uptake was significantly correlated with the Ki-67 proliferation index (rho=0.817, p=0.007).

Conclusion

These findings indicate that FLT PET is useful for evaluating tumor grade and cellular proliferation in brain tumors. It displayed high sensitivity and good contrast in evaluating brain lesions that showed similar or decreased uptake compared with normal gray matter on FDG PET. FLT PET, however, did not appear to be sufficiently useful for differentiating tumors from nontumorous lesions.

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References

  1. Shields AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-Crews JM, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med 1998;4(11):1334–6.

    Article  CAS  PubMed  Google Scholar 

  2. Wagner M, Seitz U, Buck A, Neumaier B, Schultheiss S, Bangerter M, et al. 3′-[18F]fluoro-3′-deoxythymidine([18F]-FLT) as positron emission tomography tracer for imaging proliferation in a murine B-cell lymphoma model and in the human disease. Cancer Res 2003;63:2681–7.

    CAS  PubMed  Google Scholar 

  3. Eary JF, Mankoff DA, Spence AM, Berger MS, Olshen A, Link JM, et al. 2-[C-11]thymidine imaging of malignant brain tumors. Cancer Res 1999;59:615–21.

    CAS  PubMed  Google Scholar 

  4. Schifter T, Hoffman JM, Hanson MW, Boyko OB, Beam C, Paine S, et al. Serial FDG-PET studies in the prediction of survival in patients with primary tumors. J Comput Assist Tomogr 1993;17(4):509–16.

    Google Scholar 

  5. Kim CK, Gupta NC, Chandramouli B, Alavi A. Standardized uptake values of FDG: body surface area correction is preferable to body weight correction. J Nucl Med 1994;35:164–7.

    CAS  PubMed  Google Scholar 

  6. Herholz K, Pietrzyk U, Voges J, Schroder R, Halber M, Treuer H, et al. Correlation of glucose consumption and tumor cell density in astrocytomas. A stereotactic PET study. J Neurosurg 1993;79:853–8.

    Google Scholar 

  7. Zasadny KR, Wahl RL. Standardized uptake values of normal fissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose: variations with body weight and a method for correction. Radiology 1993;189:847–50.

    CAS  PubMed  Google Scholar 

  8. Delbeke D, Meyerowitz C, Lapidus RL, Maciunas RJ, Jennings MT, Moots PL, et al. Optimal cutoff levels of F-18 fluorodeoxyglucose uptake in the differentiation of low-grade from high-grade brain tumors with PET. Radiology 1995;195:47–52.

    CAS  PubMed  Google Scholar 

  9. Kaschten B, Stevenaert A, Sadzot B, Deprez M, Degueldre C, Del Fiore G, et al. Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine. J Nucl Med 1998;39:778–85.

    CAS  PubMed  Google Scholar 

  10. Weber W, Bartenstein P, Gross MW, Kinzel D, Daschner H, Feldmann HJ, et al. Fluorine-18-FDG PET and iodine-123-IMT SPECT in the evaluation of brain tumors. J Nucl Med 1997;38:802–8.

    CAS  PubMed  Google Scholar 

  11. Oriuchi N, Tomiyoshi K, Inoue T, Ahmad K, Sarwar M, Tokunaga M, et al. Independent thallium-201 accumulation and fluorine-18-fluorodeoxyglucose metabolism in glioma. J Nucl Med 1996;37:457–62.

    Google Scholar 

  12. Chung JK, Kim YK, Kim SK, Lee YJ, Paek S, Yeo JS, et al. Usefulness of 11C-methionine PET in the evaluation of brain lesions that are hypo- or isometabolic on 18F-FDG PET. Eur J Nucl Med Mol Imaging 2002;29:176–82.

    Article  CAS  PubMed  Google Scholar 

  13. Alavi JB, Alavi A, Chawluk J, Kushner M, Powe J, Hickey W, et al. Positron emission tomography in patients with glioma. A predictor of prognosis. Cancer 1988;62:1074–78.

    CAS  PubMed  Google Scholar 

  14. Inoue T, Shibasaki T, Oriuchi N, Aoyagi K, Tomiyoshi K, Amano S, et al. 18Fα-methyl tyrosine PET studies in patients with brain tumors. J Nucl Med 1999;40:399–405.

    CAS  PubMed  Google Scholar 

  15. Tomiyoshi K, Amed K, Muhammad S, Higuchi T, Inoue T, Endo K, et al. Synthesis of isomers of 18F labelled amino acid radiopharmaceutical: 2- and 3-L−18F-alpha-methyltyrosine using a separation and purification system. Nucl Med Commun 1997;18:169–75.

    CAS  PubMed  Google Scholar 

  16. Ogawa T, Kanno I, Shishido F, Inugami A, Higano S, Fujita H, et al. Clinical value of PET with 18F-fluorodeoxyglucose and L-methyl-11C-methionine for diagnosis of recurrent brain tumor and radiation injury. Acta Radiol 1991;32:197–202.

    CAS  PubMed  Google Scholar 

  17. Shields AF, Grierson JR, Kozawa SM, Zheng M. Development of labeled thymidine analogs for imaging tumor proliferation. Nucl Med Biol 1996;23:17–22.

    Article  CAS  PubMed  Google Scholar 

  18. Grierson JR, Shields AF. Radiosynthesis of 3′-deoxy-3′-[18F]fluorothymidine: [18F]FLT for imaging of cellular proliferation in vivo. Nucl Med Biol 2000;27:143–56.

    Article  CAS  PubMed  Google Scholar 

  19. Mier W, Haberkorn U, Eisenhut M. [18F]FLT; portrait of a proliferation marker. Eur J Nucl Med Mol Imaging 2002;29:165–9.

    Article  CAS  PubMed  Google Scholar 

  20. Francis DL, Visvikis D, Costa DC, Arulampalam TH, Townsend C, Luthra SK, et al. Potential impact of [18F]3′-deoxy-3′-fluorothymidine versus [18F]fluoro-2-deoxy-D-glucose in positron emission tomography for colorectal cancer. Eur J Nucl Med Mol Imaging 2003;30:988–94.

    Article  CAS  PubMed  Google Scholar 

  21. Seitz U, Wagner M, Neumaier B, Wawra E, Glatting G, Leder G, et al. Evaluation of pyrimidine metabolising enzymes and in vitro uptake of 3′-[18F]fluoro-3′-deoxythymidine ([18F]FLT) in pancreatic cancer cell lines. Eur J Nucl Med Mol Imaging 2002;29:1174–81.

    Article  CAS  PubMed  Google Scholar 

  22. Vesselle H, Grierson J, Muzi M, Pugsley JM, Schmidt RA, Rabinowitz P, et al. In vivo validation of 3′deoxy-3′-[18F]fluorothymidine ([18F]FLT) as a proliferation imaging tracer in humans: correlation of [18F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors. Clin Cancer Res 2002;8:3315–23.

    CAS  PubMed  Google Scholar 

  23. Buck AK, Schirrmeister H, Hetzel M, Von Der Heide M, Halter G, Glatting G, et al. 3-deoxy-3-[18F]fluorothymidine-positron emission tomography for noninvasive assessment of proliferation in pulmonary nodules. Cancer Res 2002;62:3331–4.

    CAS  PubMed  Google Scholar 

  24. Dittmann H, Dohmen BM, Kehlbach R, Bartusek G, Pritzkow M, Sarbia M, et al. Early changes in [18F]FLT uptake after chemotherapy: an experimental study. Eur J Nucl Med Mol Imaging 2002;29:1462–9.

    Article  CAS  PubMed  Google Scholar 

  25. Vijayalakshmi D, Belt JA. Sodium-dependent nucleoside transport in mouse intestinal epithelial cells. Two transport systems with differing substrate specificities. J Biol Chem 1988;263:19419–23.

    Google Scholar 

  26. Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 2002;61(3):215–25.

    Google Scholar 

  27. Oh SJ, Mosdzianowski C, Chi DY, Kim JY, Kang SH, Ryu JS. Fully automated synthesis system of 3′-deoxy-3′-[18F]fluorothymidine. Nucl Med Biol 2004;31:803–9.

    Google Scholar 

  28. Di Chiro G. Positron emission tomography using [18F]fluorodeoxyglucose in brain tumors. A powerful diagnostic and prognostic tool. Invest Radiol 1987;22:360–71.

    PubMed  Google Scholar 

  29. Di Chiro G, DeLaPaz RL, Brooks RA, Sokoloff L, Kornblith PL, Smith BH, et al. Glucose utilization of cerebral gliomas measured by [18F]fluorodeoxyglucose and positron emission tomography. Neurology 1982;32:1323–9.

    Google Scholar 

  30. Tyler JL, Diksic M, Villemure JG, Evans AC, Meyer E, Yamamoto YL, et al. Metabolic and hemodynamic evaluation of gliomas using positron emission tomography. J Nucl Med 1987;28:1123–33.

    Google Scholar 

  31. Sasaki M, Kuwabara Y, Yoshida T, Nakagawa M, Fukumura T, Mihara F, et al. A comparative study of thallium-201 SPET, carbon-11 methionine PET and fluorine-18 fluorodeoxyglucose PET for the differentiation of astrocytic tumours. Eur J Nucl Med 1998;25:1261–9.

    Google Scholar 

  32. Patronas P, Brooks RA, DeLaPaz RL, Smith BH, Kornblith PL, Di Chiro G. Glycolytic rate (PET) and contrast enhancement (CT) in human cerebral gliomas. Am J Neuroradiol 1983;4:533–5.

    Google Scholar 

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Authors and Affiliations

  1. Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap-dong, Songpa-gu, Seoul, 138-736, Korea

    Seung Jin Choi, Jae Seung Kim, Seung Jun Oh, Jeong Seok Yeo, Jin Sook Ryu & Dae Hyuk Moon

  2. Department of Neurosurgery, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Korea

    Jeong Hoon Kim, Jeong Gyo Lee, Chang Jin Kim & Young Shin Ra

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  1. Seung Jin Choi
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Choi, S.J., Kim, J.S., Kim, J.H. et al. [18F]3′-deoxy-3′-fluorothymidine PET for the diagnosis and grading of brain tumors. Eur J Nucl Med Mol Imaging 32, 653–659 (2005). https://doi.org/10.1007/s00259-004-1742-3

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