Skip to main content

Advertisement

Log in

[18F]FLT-PET in oncology: current status and opportunities

  • Review Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

In recent years, [18F]-fluoro-3′-deoxy-3′-L-fluorothymidine ([18F]FLT) has been developed as a proliferation tracer. Imaging and measurement of proliferation with PET could provide us with a non-invasive staging tool and a tool to monitor the response to anticancer treatment. In this review, the basis of [18F]FLT as a proliferation tracer is discussed. Furthermore, an overview of the current status of [18F]FLT-PET research is given. The results of this research show that although [18F]FLT is a tracer that visualises cellular proliferation, it also has certain limitations. In comparison with the most widely used PET tracer, [18F]FDG, [18F]FLT uptake is lower in most cases. Furthermore, [18F]FLT uptake does not always reflect the tumour cell proliferation rate, for example during or shortly after certain chemotherapy regimens. The opportunities provided by, and the limitations of, [18F]FLT as a proliferation tracer are addressed in this review, and directions are given for further research, taking into account the strong and weak points of the new tracer.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Munch-Petersen B, Cloos L, Jensen HK, Tyrsted G. Human thymidine kinase 1. Regulation in normal and malignant cells. Adv Enzyme Regul 1995;35:69–89.

    Article  CAS  PubMed  Google Scholar 

  2. Boothman DA, Davis TW, Sahijdak WM. Enhanced expression of thymidine kinase in human cells following ionizing radiation. Int J Radiat Oncol Biol Phys 1994;30:391–8.

    CAS  PubMed  Google Scholar 

  3. Kauffman MG, Kelly TJ. Cell cycle regulation of thymidine kinase: residues near the carboxyl terminus are essential for the specific degradation of the enzyme at mitosis. Mol Cell Biol 1991;11:2538–46.

    Google Scholar 

  4. Rasey JS, Grierson JR, Wiens LW, Kolb PD, Schwartz JL. Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells. J Nucl Med 2002;43:1210–7.

    CAS  PubMed  Google Scholar 

  5. Bardot V, Dutrillaux AM, Delattre JY, Vega F, Poisson M, Dutrillaux B, et al. Purine and pyrimidine metabolism in human gliomas: relation to chromosomal aberrations. Br J Cancer 1994;70:212–8.

    CAS  PubMed  Google Scholar 

  6. Cole PD, Smith AK, Kamen BA. Osteosarcoma cells, resistant to methotrexate due to nucleoside and nucleobase salvage, are sensitive to nucleoside analogs. Cancer Chemother Pharmacol 2002;50:111–6.

    Article  CAS  PubMed  Google Scholar 

  7. Schwartz JL, Tamura Y, Jordan R, Grierson JR, Krohn KA. Monitoring tumor cell proliferation by targeting DNA synthetic processes with thymidine and thymidine analogs. J Nucl Med 2003;44:2027–32.

    PubMed  Google Scholar 

  8. 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  Google Scholar 

  9. Mirjolet JF, Barberi-Heyob M, Merlin JL, Marchal S, Etienne MC, Milano G, et al. Thymidylate synthase expression and activity: relation to S-phase parameters and 5-fluorouracil sensitivity. Br J Cancer 1998;78:62–8.

    CAS  PubMed  Google Scholar 

  10. Tsurusawa M, Niwa M, Katano N, Fujimoto T. Flow cytometric analysis by bromodeoxyuridine/DNA assay of cell cycle perturbation of methotrexate-treated mouse L1210 leukemia cells. Cancer Res 1988;48:4288–93.

    CAS  PubMed  Google Scholar 

  11. Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol 2000;182:311–22.

    Article  CAS  PubMed  Google Scholar 

  12. Spyratos F, Ferrero-Pous M, Trassard M, Hacene K, Phillips E, Tubiana-Hulin M, et al. Correlation between MIB-1 and other proliferation markers: clinical implications of the MIB-1 cutoff value. Cancer 2002;94:2151–9.

    Article  CAS  PubMed  Google Scholar 

  13. Hartmann H, Vogt MW, Durno AG, Hirsch MS, Hunsmann G, Eckstein F. Enhanced in vitro inhibition of HIV-1 replication by 3′-fluoro-3′-deoxythymidine compared to several other nucleoside analogs. AIDS Res Hum Retroviruses 1988;4:457–66.

    CAS  PubMed  Google Scholar 

  14. Flexner C, van der HC, Jacobson MA, Powderly W, Duncanson F, Ganes D, et al. Relationship between plasma concentrations of 3′-deoxy-3′-fluorothymidine (alovudine) and antiretroviral activity in two concentration-controlled trials. J Infect Dis 1994;170:1394–403.

    CAS  PubMed  Google Scholar 

  15. 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  Google Scholar 

  16. Martin SJ, Eisenbarth JA, Wagner-Utermann U, Mier W, Haberkorn U, Eisenhut M. [18F]FLT: 18F labeling of 3-BOC-1-(2-deoxy-3-O-nosyl-5-O-trityl-beta-D-lyxofuranosyl) thymine and other thymine derivates. J Nucl Med 2000;41:255.

    Google Scholar 

  17. Mosdzianowski C, Nader M, Korenjak C, Martin SJ, Eisenbarth JA. Automated FLT syntheses using 3-N-Boc-1-(5-O-(4,4′-dimethoxytrityl)-3-O-nosyl-2-deoxy-beta-D- lyxofuranosyl)thymidine as precursor. Eur J Nucl Med Mol Imaging 2001;28:1228.

    Google Scholar 

  18. Yun M, Oh SJ, Ha HJ, Ryu JS, Moon DH. High radiochemical yield synthesis of 3′-deoxy-3′-[18F]fluorothymidine using (5′-O-dimethoxytrityl-2′-deoxy-3′-O-nosyl-beta-D- threo pentofuranosyl)thymine and its 3-N-BOC-protected analogue as a labeling precursor. Nucl Med Biol 2003;30:151–7.

    Article  Google Scholar 

  19. Moon BS, Shim AY, Kim DW, Kim SE, Yand SD, Chi DY. New synthetic method for [18F]-3′-deoxy-3′-fluorothymidine using a nosylate precursor in ionic liquid ([bmim][OTf]). J Labelled Cpd Radiopharm 2003;46:S122.

    Google Scholar 

  20. Machulla HJ, Blochter A, Kuntzsch M, Piert M, Wei R, Grierson JR. Simplified labeling approach for synthesizing 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT). J Radioanal Nucl Chem 2000;243:843–6.

    Article  CAS  Google Scholar 

  21. Cleij MC, Steel CJ, Brady F, Ell PJ. An improved synthesis of 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) and the fate of the precursor, 2,3′-anhydro-5′-O-(4,4′-dimethoxytrityl)-thymidine. J Labelled Cpd Radiopharm 2001;44:S871–3.

    Article  Google Scholar 

  22. 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 

  23. Carter EA, McKuster K, Syed SZ, Thompkins RG. Comparison of 18FLT with 18FDG for differentiation between tumor and focal sites of infection in rats. J Nucl Med 2002;43:266.

    Google Scholar 

  24. Lee TS, Shim AY, Hwang WT, Ahn SH, Sung HD, Chung HK, et al. Comparison of FDG, FET and FLT for differentiation between tumor and abscess in rats. In: SNM 50th Annual Meeting 2003.

  25. Van Waarde A, Cobben DCP, Suurmeijer AJH, Maas B, Vaalburg W, De Vries EFJ, et al. Selectivity of 3′-deoxy-3′-[18F]fluorothymidine (FLT) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) for tumor versus inflammation in a rodent model. J Nucl Med 2004;45:695–700.

    CAS  PubMed  Google Scholar 

  26. Francis DL, Loizidou M, Visvikis D, DeVos S, Luthra SK, Taylor I. Monitoring 5-fluorouracil chemotherapy response in colorectal cancer using positron emission tomography. Eur J Surg Oncol 2003;29:789.

    Google Scholar 

  27. Yeo JS, Lim SJ, Oh SJ, Ryu JS, Yun MK, Moon DH. Comparison of F-18 FLT uptake with F-18 FDG for early evaluation of chemotherapy response in human cancer cell lines. J Nucl Med 2003;44:81.

    Google Scholar 

  28. Barthel H, Cleij MC, Collingridge DR, Hutchinson OC, Osman S, He Q, et al. 3′-deoxy-3′-[18F]fluorothymidine as a new marker for monitoring tumor response to antiproliferative therapy in vivo with positron emission tomography. Cancer Res 2003;63:3791–8.

    CAS  PubMed  Google Scholar 

  29. Huang SC, McBride W, Stout D, Sitko J, Liao YP, Daigle J, et al. Post-irradiation temporal changes in glucose metabolism and cell proliferation in implanted murine tumors as measured by FDG and FLT PET. J Nucl Med 2002;43:25.

    Google Scholar 

  30. Oyama N, Ponde DE, Dence C, Kim J, Tai YC, Welch MJ. Monitoring of therapy in androgen-dependent prostate tumor model by measuring tumor proliferation. J Nucl Med 2004;45:519–25.

    PubMed  Google Scholar 

  31. Bonab AA, Weise SW, Syed SZ, Martyn FS, Carter EA, Fischman AJ. Monitoring treatment with a CDK2 inhibitor by microPET with 18F-FLT in a nude mouse tumor model. In: SNM 50th Annual Meeting 2003.

  32. Waldherr C, Safaei A, Mellinghoff I, Tran C, Stout D, Vranjesevic D, et al. MicroPET with 18F-FLT and 18F-FDG for monitoring targeted tumor therapy in SCID mice. J Nucl Med 2003;44:80–1.

    Google Scholar 

  33. Nottebrock H, Then R. Thymidine concentrations in serum and urine in different animal species and man. Biochem Pharmacol 1977;26:2175–9.

    Article  CAS  PubMed  Google Scholar 

  34. Kong XB, Zhu QY, Vidal PM, Watanabe KA, Polsky B, Armstrong D, et al. Comparisons of anti-human immunodeficiency virus activities, cellular transport, and plasma and intracellular pharmacokinetics of 3′-fluoro-3′-deoxythymidine and 3′-azido-3′-deoxythymidine. Antimicrob Agents Chemother 1992;36:808–18.

    CAS  PubMed  Google Scholar 

  35. Munch-Petersen B, Cloos L, Tyrsted G, Eriksson S. Diverging substrate specificity of pure human thymidine kinases 1 and 2 against antiviral dideoxynucleosides. J Biol Chem 1991;266:9032–8.

    CAS  PubMed  Google Scholar 

  36. Jerusalem G, Hustinx R, Beguin Y, Fillet G. PET scan imaging in oncology. Eur J Cancer 2003;39:1525–34.

    Article  CAS  PubMed  Google Scholar 

  37. Minn H, Clavo AC, Grenman R, Wahl RL. In vitro comparison of cell proliferation kinetics and uptake of tritiated fluorodeoxyglucose and L-methionine in squamous-cell carcinoma of the head and neck. J Nucl Med 1995;36:252–8.

    CAS  PubMed  Google Scholar 

  38. Higashi K, Clavo AC, Wahl RL. In vitro assessment of 2-fluoro-2-deoxy-D-glucose, L-methionine and thymidine as agents to monitor the early response of a human adenocarcinoma cell line to radiotherapy. J Nucl Med 1993;34:773–9.

    CAS  PubMed  Google Scholar 

  39. Haberkorn U, Ziegler SI, Oberdorfer F, Trojan H, Haag D, Peschke P, et al. FDG uptake, tumor proliferation and expression of glycolysis associated genes in animal tumor models. Nucl Med Biol 1994;21:827–34.

    Article  CAS  PubMed  Google Scholar 

  40. 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;4:1334–6.

    Article  CAS  PubMed  Google Scholar 

  41. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001;285:914–24.

    Article  CAS  PubMed  Google Scholar 

  42. Croft DR, Trapp J, Kernstine K, Kirchner P, Mullan B, Galvin J, et al. FDG-PET imaging and the diagnosis of non-small cell lung cancer in a region of high histoplasmosis prevalence. Lung Cancer 2002;36:297–301.

    Article  PubMed  Google Scholar 

  43. Cerfolio RJ, Ojha B, Bryant AS, Bass CS, Bartalucci AA, Mountz JM. The role of FDG-PET scan in staging patients with nonsmall cell carcinoma. Ann Thorac Surg 2003;76:861–6.

    Article  PubMed  Google Scholar 

  44. Buck AK, Schirrmeister H, Hetzel M, Von Der HM, 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.

    Google Scholar 

  45. 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.

    Google Scholar 

  46. Dittmann H, Dohmen BM, Paulsen F, Wehrmann M, Bares R. [18F]FLT PET for diagnosis and staging of thoracic tumors. J Nucl Med 2003;44:134.

    PubMed  Google Scholar 

  47. Yap CS, Schiepers C, Quon A, Silverman DH, Satyamurthy N, Phelps ME, et al. A comparison between [F-18]fluorodeoxyglucose (FDG) and [F-18]3′-deoxy-3′-fluorothymidine (FLT) uptake in solitary pulmonary nodules and lung cancer. J Nucl Med 2003;44:123.

    Google Scholar 

  48. Dittmann H, Dohmen BM, Paulsen F, Eichhorn K, Eschmann SM, Horger M, et al. [18F]FLT PET for diagnosis and staging of thoracic tumours. Eur J Nucl Med Mol Imaging 2003;30:1407–12.

    Article  Google Scholar 

  49. Buck AK, Halter G, Schirrmeister H, Kotzerke J, Wurziger I, Glatting G, et al. Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG. J Nucl Med 2003;44:1426–31.

    CAS  PubMed  Google Scholar 

  50. Cobben DC, Elsinga PH, Hoekstra HJ, Suurmeijer AJ, Vaalburg W, Maas B, et al. Is 18F-3′-fluoro-3′-deoxy-L-thymidine useful for the staging and restaging of non-small cell lung cancer? J Nucl Med 2004;45:1677–82.

    PubMed  Google Scholar 

  51. Shields AF, Dohmen BM, Mangner TJ, Lawhorn-Crews JM, Machulla HJ, Muzik O, et al. Imaging of thoracic tumors with 18F-FLT. J Nucl Med 2000;41:74.

    Google Scholar 

  52. Silverman DH, Pio BS, Satyamurthy N, Park CK, Chap L, Pegram M, et al. Monitoring effects of breast cancer chemotherapy with fluorodeoxyglucose and fluoro-L-thymidine. J Nucl Med 2002;43:311.

    Google Scholar 

  53. Smyczek-Gargya B, Fersis N, Dittmann H, Vogel U, Reischl G, Machulla HJ, et al. PET with [18F]fluorothymidine for imaging of primary breast cancer: a pilot study. Eur J Nucl Med Mol Imaging 2004;31:720–4.

    Article  PubMed  Google Scholar 

  54. Pio BS, Park CK, Satyamurthy N, Chap L, Pegram M, Czernin J et al. Monitoring early and long-term effects of breast cancer chemotherapy with fluorodeoxyglucose and fluoro-L-thymidine. In: ASCO Conference 2003.

  55. Hou MF, Chen YL, Tseng TF, Lin CM, Chen MS, Huang CJ, et al. Evaluation of serum CA27.29, CA15–3 and CEA in patients with breast cancer. Kaohsiung J Med Sci 1999;15:520–8.

    CAS  PubMed  Google Scholar 

  56. Giuliano AE, Jones RC, Brennan M, Statman R. Sentinel lymphadenectomy in breast cancer. J Clin Oncol 1997;15:2345–50.

    CAS  PubMed  Google Scholar 

  57. Veronesi U, Galimberti V, Zurrida S, Pigatto F, Veronesi P, Robertson C, et al. Sentinel lymph node biopsy as an indicator for axillary dissection in early breast cancer. Eur J Cancer 2001;37:454–8.

    Article  CAS  PubMed  Google Scholar 

  58. Vander BT, Pauwels S, Lambotte L, Labar D, De Maeght S, Stroobandt G, et al. Brain tumor imaging with PET and 2-[carbon-11]thymidine. J Nucl Med 1994;35:974–82.

    PubMed  Google Scholar 

  59. 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 

  60. Dohmen BM, Shields AF, Grierson JR, Kuntzsch M, Reimold M, Sloan A, et al. [18F]FLT-PET in brain tumors. J Nucl Med 2000;41Suppl:216P.

    Google Scholar 

  61. Bendaly EA, Sloan AE, Dohmen BM, Mangner TJ, Machulla HJ, Bares R, et al. Use of 18F-FLT-PET to assess the metabolic activity of primary and metastatic brain tumors [abstract]. J Nucl Med 2002;111.

  62. Garlip G, Dittmar C, Kracht L, Thomas AV, Herholz K, Heiss WD, et al. Identification of DNA and amino acid metabolism in human gliomas by PET. J Nucl Med 2003;44:167.

    Google Scholar 

  63. Nitzsche EU, Walter M, Schirp U, Machulla HJ, Mueller J. Combined PET maging of proliferation and glycolysis for follow up of brachytherapy in brain tumors. In: SNM 50th Annual Meeting 2003.

  64. Huebner RH, Park KC, Shepherd JE, Schwimmer J, Czernin J, Phelps ME, et al. A meta-analysis of the literature for whole-body FDG PET detection of recurrent colorectal cancer. J Nucl Med 2000;41:1177–89.

    Google Scholar 

  65. 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 

  66. Francis DL, Freeman A, Visvikis D, Costa DC, Luthra SK, Novelli M, et al. In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography. Gut 2003;52:1602–6.

    Article  CAS  PubMed  Google Scholar 

  67. Jerusalem G, Beguin Y, Fassotte MF, Najjar F, Paulus P, Rigo P, et al. Whole-body positron emission tomography using 18F-fluorodeoxyglucose for posttreatment evaluation in Hodgkin’s disease and non-Hodgkin’s lymphoma has higher diagnostic and prognostic value than classical computed tomography scan imaging. Blood 1999;94:429–33.

    CAS  PubMed  Google Scholar 

  68. 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 

  69. Buck AK, Pitterle K, Schirrmeister H, Bommer M, Glatting G, Neumaier B, et al. [18F]FLT positron emission tomography for imaging non-Hodgkin’s lymphoma and assessment of proliferative activity. J Nucl Med 2003; 44:188–9.

    Google Scholar 

  70. Tominaga K, Yamaguchi Y, Nozawa Y, Abe M, Wakasa H. Proliferation in non-Hodgkin’s lymphomas as determined by immunohistochemical double staining for Ki-67. Hematol Oncol 1992; 10:163–169.

    CAS  PubMed  Google Scholar 

  71. Cobben DC, Elsinga PH, Suurmeijer AJ, Vaalburg W, Maas B, Jager PL, et al. Detection and grading of soft tissue sarcomas of the extremities with (18)F-3′-fluoro-3′-deoxy-L-thymidine. Clin Cancer Res 2004;10:1685–90.

    CAS  PubMed  Google Scholar 

  72. van Ginkel RJ, Hoekstra HJ, Pruim J, Nieweg OE, Molenaar WM, Paans AM, et al. FDG-PET to evaluate response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcoma. J Nucl Med 1996;37:984–90.

    PubMed  Google Scholar 

  73. van Ginkel RJ, Kole AC, Nieweg OE, Molenaar WM, Pruim J, Koops HS, et al. L-[1-11C]-tyrosine PET to evaluate response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcoma and skin cancer. J Nucl Med 1999;40:262–7.

    PubMed  Google Scholar 

  74. Cobben DC, Koopal S, Tiebosch AT, Jager PL, Elsinga PH, Wobbes T, et al. New diagnostic techniques in staging in the surgical treatment of cutaneous malignant melanoma. Eur J Surg Oncol 2002;28:692–700.

    Article  CAS  PubMed  Google Scholar 

  75. Rinne D, Baum RP, Hor G, Kaufmann R. Primary staging and follow-up of high risk melanoma patients with whole-body 18F-fluorodeoxyglucose positron emission tomography: results of a prospective study of 100 patients. Cancer 1998;82:1664–71.

    Article  CAS  PubMed  Google Scholar 

  76. Macfarlane DJ, Sondak V, Johnson T, Wahl RL. Prospective evaluation of 2-[18F]-2-deoxy-D-glucose positron emission tomography in staging of regional lymph nodes in patients with cutaneous malignant melanoma. J Clin Oncol 1998;16:1770–6.

    CAS  PubMed  Google Scholar 

  77. Holder WD Jr, White RL Jr, Zuger JH, Easton EJ Jr, Greene FL. Effectiveness of positron emission tomography for the detection of melanoma metastases. Ann Surg 1998; 227:764–769.

    Article  PubMed  Google Scholar 

  78. Havenga K, Cobben DC, Oyen WJ, Nienhuijs S, Hoekstra HJ, Ruers TJ, Wobbes T. Fluorodeoxyglucose-positron emission tomography and sentinel lymph node biopsy in staging primary cutaneous melanoma. Eur J Surg Oncol 2003;29:662–4.

    Article  CAS  PubMed  Google Scholar 

  79. Cobben DC, Jager PL, Elsinga PH, Maas B, Suurmeijer AJ, Hoekstra HJ. 3′-18F-fluoro-3′-deoxy-L-thymidine: a new tracer for staging metastatic melanoma? J Nucl Med 2003;44:1927–32.

    CAS  PubMed  Google Scholar 

  80. Cobben DC, van der Laan BF, Maas B, Vaalburg W, Suurmeijer AJ, Hoekstra HJ, et al. 18F-FLT PET for visualization of laryngeal cancer: comparison with 18F-FDG PET. J Nucl Med 2004;45:226–31.

    Google Scholar 

  81. Gati WP, Misra HK, Knaus EE, Wiebe LI. Structural modifications at the 2′- and 3′-positions of some pyrimidine nucleosides as determinants of their interaction with the mouse erythrocyte nucleoside transporter. Biochem Pharmacol 1984;33:3325–31.

    Article  CAS  PubMed  Google Scholar 

  82. Eriksson S, Kierdaszuk B, Munch-Petersen B, Oberg B, Johansson NG. Comparison of the substrate specificities of human thymidine kinase 1 and 2 and deoxycytidine kinase toward antiviral and cytostatic nucleoside analogs. Biochem Biophys Res Commun 1991;176:586–92.

    CAS  PubMed  Google Scholar 

  83. Shields AF. PET imaging with 18F-FLT and thymidine analogs: promise and pitfalls. J Nucl Med 2003;44:1432–4.

    CAS  PubMed  Google Scholar 

  84. Bergstrom M, Lu L, Fasth KJ, Wu F, Bergstrom-Pettermann E, Tolmachev V, et al. In vitro and animal validation of bromine-76-bromodeoxyuridine as a proliferation marker. J Nucl Med 1998;39:1273–9.

    CAS  PubMed  Google Scholar 

  85. Conti PS, Alauddin MM, Fissekis JR, Schmall B, Watanabe KA. Synthesis of 2′-fluoro-5-[11C]-methyl-1-beta-D-arabinofuranosyluracil ([11C]-FMAU): a potential nucleoside analog for in vivo study of cellular proliferation with PET. Nucl Med Biol 1995;22:783–89.

    Article  CAS  PubMed  Google Scholar 

  86. Mangner TJ, Klecker RW, Anderson L, Shields AF. Synthesis of 2′-deoxy-2′-[18F]fluoro-beta-D-arabinofuranosyl nucleosides, [18F]FAU, [18F]FMAU, [18F]FBAU and [18F]FIAU, as potential PET agents for imaging cellular proliferation. Synthesis of [18F]labelled FAU, FMAU, FBAU, FIAU. Nucl Med Biol 2003;30:215–24.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Dutch Cancer Society (grant no. 2000–2299).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lukas B. Been.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Been, L.B., Suurmeijer, A.J.H., Cobben, D.C.P. et al. [18F]FLT-PET in oncology: current status and opportunities. Eur J Nucl Med Mol Imaging 31, 1659–1672 (2004). https://doi.org/10.1007/s00259-004-1687-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-004-1687-6

Keywords

Navigation