Skip to main content
Log in

3′-Deoxy-3′-[F-18]Fluorothymidine Positron Emission Tomography in Patients with Recurrent Glioblastoma Multiforme: Comparison with Gd-DTPA Enhanced Magnetic Resonance Imaging

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Introduction

The accumulation of 3′-deoxy-3′-[F-18]fluorothymidine (FLT) on positron emission tomography (PET) images in patients with glioblastoma multiforme was evaluated and correlated with gadopentetate dimeglumine (Gd-DTPA) enhancement in magnetic resonance images (MRIs).

Methods

FLT studies in 10 patients with recurrent glioblastoma multiforme were retrospectively investigated. Dynamic emission data were acquired for 60 minutes immediately after injection of FLT. The standardized uptake value (SUV) for tumor and reference tissue (contralateral hemisphere and ipsilateral cerebellum) was calculated. The volumes of the metabolically active part of the tumor (V PET) and that of the Gd-DTPA enhancing part of the tumor (V MR) were calculated.

Results

FLT uptake in tumors peaked before 5 minutes and sometimes as early as 0.5 minutes, and reached a constant level at approximately 10 minutes after injection. The reference tissue time–activity curves had an early peak and reached a constant low background level. All tumors had increased FLT uptake and showed Gd-DTPA enhancement. The SUV in tumor was significantly higher than that in the reference tissue (P<0.0001). A significant correlation between V PET and V MR was found (P<0.0001) although there was a difference in the areas of Gd-DTPA enhancement and FLT uptake.

Conclusion

These preliminary results indicate that FLT-PET may be useful for the detection of recurrent glioblastoma multiforme. Our data in a relatively small patient population do not support a clear-cut relationship between FLT accumulation and Gd-DTPA enhancement. Further pathologic correlation will determine if it can be used for detecting recurrent tumoral disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Rohren EM, Turkington TG, Coleman RE (2004) Clinical applications of PET in oncology. Radiology 231:305–332

    PubMed  Google Scholar 

  2. Delbeke D, Meyerowitz C, Lapidus RL, et al. (1995) Optimal cutoff levels of F-18 fluorodeoxyglucose uptake in the differentiation of low-grade from high-grade brain tumors with PET. Radiology 195:47–52

    CAS  PubMed  Google Scholar 

  3. Kaschten B, Stevenaert A, Sadzot B, et al. (1998) Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine. J Nucl Med 39:778–785

    CAS  PubMed  Google Scholar 

  4. Wong TZ, van der Westhuizen GJ, Coleman RE (2002) Positron emission tomography imaging of brain tumors. Neuroimaging Clin N Am 12:615–626

    Article  PubMed  Google Scholar 

  5. Weber W, Bartenstein P, Gross MW, et al. (1997) Fluorine-18-FDG-PET and iodine-123-IMT SPECT in the evaluation of brain tumors. J Nucl Med 38:802–808

    CAS  PubMed  Google Scholar 

  6. Oriuchi N, Tomiyoshi K, Inoue T, et al. (1996) Independent thallium-201 accumulation and fluorine-18-fluorodeoxyglucose metabolism in glioma. J Nucl Med 37:457–462

    CAS  PubMed  Google Scholar 

  7. Ricci PE, Karis JP, Heiserman JE, et al. (1998) Differentiating recurrent tumor from radiation necrosis: time for re-evaluation of positron emission tomography? AJNR 19:407–413

    CAS  PubMed  Google Scholar 

  8. Chung JK, Kim YK, Kim SK, et al. (2002) 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 29:176–182

    Article  CAS  PubMed  Google Scholar 

  9. Shields AF, Grierson JR, Dohmen BM, et al. (1998) Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med 4:1334–1336

    Article  CAS  PubMed  Google Scholar 

  10. Eary JF, Mankoff DA, Spence AM, et al. (1999) 2-[C-11]thymidine imaging of malignant brain tumors. Cancer Res 59:615–621

    CAS  PubMed  Google Scholar 

  11. Inoue T, Shibasaki T, Oriuchi N, et al. (1999) 18F α-methyl tyrosine PET studies in patients with brain tumors. J Nucl Med 40:399–405

    CAS  PubMed  Google Scholar 

  12. Ogawa T, Kanno I, Shishido F, et al. (1991) Clinical value of PET with 18F-fluorodeoxyglucose and l-methyl-11C-methionine for diagnosis of recurrent brain tumor and radiation injury. Acta Radiol 32:197–202

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. Grierson JR, Shields AF (2000) Radiosynthesis of 3′-deoxy-3′-[18F]fluorothymidine: [18F]FLT for imaging of cellular proliferation in vivo. Nucl Med Biol 27:143–156

    Article  CAS  PubMed  Google Scholar 

  15. Mier W, Haberkorn U, Eisenhut M (2002) [18F]FLT: portrait of a proliferation marker. Eur J Nucl Med Mol Imaging 29:165–169

    Article  CAS  PubMed  Google Scholar 

  16. Rasey JS, Grierson JR, Wiens LW, et al. (2002) Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells. J Nucl Med 43:1210–1217

    CAS  PubMed  Google Scholar 

  17. Buck AK, Halter G, Schirrmeister H, et al. (2003) Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG. J Nucl Med 44:1426–1431

    CAS  PubMed  Google Scholar 

  18. Vesselle H, Grierson J, Muzi M, et al. (2002) 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 8:3315–3332

    CAS  PubMed  Google Scholar 

  19. Francis DL, Visvikis D, Costa DC, et al. (2003) Potential impact of [18F]3′-deoxy-3′-flurorothymidine versus [18F]fluoro-2-deoxy-d-glucose in positron emission tomography for colorectal cancer. Eur J Nucl Med Mol Imaging 30:988–994

    Article  CAS  PubMed  Google Scholar 

  20. Francis DL, Freeman A, Visvikis D, et al. (2003) In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography. Gut 52:1602–1606

    Article  CAS  PubMed  Google Scholar 

  21. Cobben DC, Jager PL, Elsinga PH, et al. (2003) 3′-18F-Fluoro-3′-deoxy-l-thymidine: a new tracer for staging metastatic melanoma? J Nucl Med 44:1927–1932

    CAS  PubMed  Google Scholar 

  22. Cobben DC, Van der Laan BF, Maas B, et al. (2004) 18F-FLT-PET for visualization of laryngeal cancer: comparison with 18F-FDG-PET. J Nucl Med 45:226–231

    PubMed  Google Scholar 

  23. Cobben DC, Elsinga PH, Suurmeijer AJ, et al. (2004) Detection and grading of soft tissue sarcomas of the extremities with 18F-3′-fluoro-3′-deoxy-l-thymidine. Clin Cancer Res 10:1685–1690

    Article  CAS  PubMed  Google Scholar 

  24. Visvikis D, Francis D, Mulligan R, et al. (2004) Comparison of methodologies for the in vivo assessment of 18FLT utilisation in colorectal cancer. Eur J Nucl Med Mol Imaging 31:169–178

    Article  CAS  PubMed  Google Scholar 

  25. Smyczek-Gargya B, Fersis N, Dittmann H, et al. (2004) PET with [18F]fluorothymidine for imaging of primary breast cancer: a pilot study. Eur J Nucl Med Mol Imaging 31:720–724

    Article  PubMed  Google Scholar 

  26. van Westreenen H, Cobben DCP, Jager PL, et al. (2005) Comparison of 18F-FLT-PET and 18F-FDG-PET in esophageal cancer. J Nucl Med 46:400–404

    PubMed  Google Scholar 

  27. Chen W, Cloughesy T, Kamdar N, et al. (2005) Imaging proliferation in brain tumors with 18F-FLT-PET: comparison with 18F-FDG. J Nucl Med 46:945–952

    CAS  PubMed  Google Scholar 

  28. Choi SJ, Kim JS, Kim JH, et al. (2005) [18F]3′-Deoxy-3′-fluorothymidine PET for the diagnosis and grading of brain tumors. Eur J Nucl Med Mol Imaging 32:653–659

    Article  PubMed  Google Scholar 

  29. Kleihues P, Louis DN, Scheithauer BW, et al. (2002) The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61:215–225

    PubMed  Google Scholar 

  30. DeGrado TR, Turkington TG, Williams JJ, Stearns CW, Hoffman JM, Coleman RE (1994) Performance characteristics of a whole-body PET scanner. J Nucl Med 35:1398–1406

    CAS  PubMed  Google Scholar 

  31. Yun M, Oh AJ, Ha HJ, Ryu JS, Moon DH (2003) High radiochemical yield synthesis of 3′-deoxy-3′-[18F]fluorothymidine using (5′-O-dimethoxytrityl-2′-deoxy-3′-O-nosyl-β-d-threo pentofuranosyl)thymine and its 3-N-BOC-protected analogue as a labeling precursor. Nucl Med Biol 30:151–157

    Article  CAS  PubMed  Google Scholar 

  32. Martin SJ, Eisenbarth JA, Wagner-Utermann U, et al. (2002) A new precursor for the radiosynthesis of [18F]FLT. Nucl Med Biol 29:263–273

    Article  CAS  PubMed  Google Scholar 

  33. Pelizzari CA, Chen GTY, Spelbring DR, Weichselbaum RR, Chen CT (1989) Accurate three-dimensional registration of CT, PET and/or MR images of the brain. J Comput Assist Tomogr 13:20–26

    CAS  PubMed  Google Scholar 

  34. Turkington TG, Hoffman JM, Jaszczak RJ, et al. (1995) Accuracy of surface fit registration for PET and MR brain images using full and incomplete brain surfaces. J Comput Assist Tomogr 19:117–124

    Article  CAS  PubMed  Google Scholar 

  35. Earnest F, Kelly PJ, Scheithauer BW, et al. (1988) Cerebral astrocytomas: histopathologic correlation of MR and CT contrast enhancement with stereotactic biopsy. Radiology 166:823–827

    PubMed  Google Scholar 

  36. Sherley JL, Kelly TJ (1988) Regulation of human thymidine kinase during the cell cycle. J Biol Chem 263:8350–8358

    CAS  PubMed  Google Scholar 

  37. Jacobs AH, Thomas A, Kracht LW, et al. (2005) 18F-fluoro-l-thymidine and 11C methylmethionine as markers of increased transport and proliferation in brain tumors. J Nucl Med 46:1948–1958

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yuka Yamamoto MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamamoto, Y., Wong, T.Z., Turkington, T.G. et al. 3′-Deoxy-3′-[F-18]Fluorothymidine Positron Emission Tomography in Patients with Recurrent Glioblastoma Multiforme: Comparison with Gd-DTPA Enhanced Magnetic Resonance Imaging. Mol Imaging Biol 8, 340–347 (2006). https://doi.org/10.1007/s11307-006-0063-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-006-0063-2

Key words

Navigation