Nuclear Medicine and Biology
Volume 36, Issue 2 , Pages 163-169 , February 2009

3′-Deoxy-3′-[18F]fluorothymidine (FLT) uptake in breast cancer cells as a measure of proliferation after doxorubicin and docetaxel treatment

  • Helmut Dittmann

      Affiliations

    • Department of Nuclear Medicine, Eberhard-Karls-University, Tuebingen D-72076, Germany
    • Corresponding Author InformationCorresponding author. Department of Nuclear Medicine, University of Tuebingen, Otfried-Mueller-Str. 14, D-72076 Tuebingen, Germany. Tel.: +49 7071 29 82179; fax: +49 7071 29 5869.
  • ,
  • Ajnur Jusufoska

      Affiliations

    • Department of Gynecology, Eberhard-Karls-University, Tuebingen D-72076, Germany
  • ,
  • Bernhard Matthias Dohmen

      Affiliations

    • Department of Nuclear Medicine, Eberhard-Karls-University, Tuebingen D-72076, Germany
  • ,
  • Brigitte Smyczek-Gargya

      Affiliations

    • Department of Gynecology, Eberhard-Karls-University, Tuebingen D-72076, Germany
  • ,
  • Nikos Fersis

      Affiliations

    • Department of Gynecology, Eberhard-Karls-University, Tuebingen D-72076, Germany
  • ,
  • Maren Pritzkow

      Affiliations

    • Department of Nuclear Medicine, Eberhard-Karls-University, Tuebingen D-72076, Germany
  • ,
  • Rainer Kehlbach

      Affiliations

    • Department of Diagnostic Radiology, Eberhard-Karls-University, Tuebingen D-72076, Germany
  • ,
  • Reinhard Vonthein

      Affiliations

    • Department of Medical Biometry, Eberhard-Karls-University, Tuebingen D-72076, Germany
  • ,
  • Hans Juergen Machulla

      Affiliations

    • Department of Nuclear Medicine, Eberhard-Karls-University, Tuebingen D-72076, Germany
  • ,
  • Roland Bares

      Affiliations

    • Department of Nuclear Medicine, Eberhard-Karls-University, Tuebingen D-72076, Germany

Received 10 October 2008 ,Accepted 25 October 2008.

References 

  1. Kim R, Osaki A, Toge T. Current and future roles of neoadjuvant chemotherapy in operable breast cancer. Clin Breast Cancer. 2005;6:223–232
  2. Bear HD, Anderson S, Smith RE, Robidoux A, Kahlenberg MS, Margolese RG, et al. A randomized trial comparing preoperative (preop) doxorubicin/cyclophosphamide (AC) to preop AC followed by preop docetaxel (T) and to preop AC followed by postoperative (postop) T in patients (pts) with operable carcinoma of the breast: results of NSABP B-27. Breast Cancer Res Treat. 2004;88(Suppl 1):26A
  3. Thomas E, Holmes FA, Smith TL, Buzdar AU, Frye DK, Fraschini G, et al. The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol. 2004;22:2294–2302
  4. 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;4:1334–1336
  5. 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;36:808–818
  6. Sherley JL, Kelly TJ. Regulation of human thymidine kinase during the cell cycle. J Biol Chem. 1988;263:8350–8358
  7. Parker WB, Cheng YC. Metabolism and mechanism of action of 5-fluorouracil. Pharmacol Ther. 1990;48:381–395
  8. Yang XL, Wang AH. Structural studies of atom-specific anticancer drugs acting on DNA. Pharmacol Ther. 1999;83:181–215
  9. Abal M, Andreu JM, Barasoain I. Taxanes: microtubule and centrosome targets, and cell cycle dependent mechanisms of action. Curr Cancer Drug Targets. 2003;3:193–203
  10. Romain S, Spyratos F, Descotes F, Daver A, Rostaing-Puissant B, Bougnoux P, et al. Prognostic of DNA-synthesizing enzyme activities (thymidine kinase and thymidylate synthase) in 908 T1-T2, N0-N1, M0 breast cancers: a retrospective multicenter study. Int J Cancer. 2000;87:860–868
  11. 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;31:720–724
  12. Kenny LM, Vigushin DM, Al-Nahhas A, Osman S, Luthra SK, Shousha S, et al. Quantification of cellular proliferation in tumor and normal tissues of patients with breast cancer by [18F]fluorothymidine-positron emission tomography imaging: evaluation of analytical methods. Cancer Res. 2005;65:10104–10112
  13. Pio BS, Park CK, Pietras R, Hsueh WA, Satyamurthy N, Pegram MD, et al. Usefulness of 3′-[F-18]fluoro-3′-deoxythymidine with positron emission tomography in predicting breast cancer response to therapy. Mol Imaging Biol. 2006;8:36–42
  14. Kenny L, Coombes RC, Vigushin DM, Al-Nahhas A, Shousha S, Aboagye EO. Imaging early changes in proliferation at 1 week post chemotherapy: a pilot study in breast cancer patients with 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography. Eur J Nucl Med Mol Imaging. 2007;34:1339–1347
  15. 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;70:212–218
  16. 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;50:111–116
  17. 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;44:2027–2032
  18. 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;29:1462–1469
  19. Nabholtz JM. Docetaxel–anthracycline combinations in metastatic breast cancer. Breast Cancer Res Treat. 2003;79(Suppl 1):3–9
  20. Yung WK. In vitro chemosensitivity testing and its clinical application in human gliomas. Neurosurg Rev. 1989;12:197–203
  21. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;8476:307–310
  22. Grierson JR, Schwartz JL, Muzi M, Jordan R, Krohn KA. Metabolism of 3′-deoxy-3′-[F-18]fluorothymidine in proliferating A549 cells: validations for positron emission tomography. Nucl Med Biol. 2004;31:829–837
  23. Barthel H, Perumal M, Latigo J, He Q, Brady F, Luthra SK, et al. The uptake of 3′-deoxy-3′-[18F]fluorothymidine into L5178Y tumors in vivo is dependent on thymidine kinase 1 protein levels. Eur J Nucl Med Mol Imaging. 2005;32:257–263
  24. 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;43:1210–1217
  25. 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;63:3791–3798
  26. Munch-Petersen B, Tyrsted G, Cloos L. Reversible ATP-dependent transition between two forms of human cytosolic thymidine kinase with different enzymatic properties. J Biol Chem. 1993;268:15621–15625
  27. van Waarde A, Been LB, Ishiwata K, Dierckx RA, Elsinga PH. Early response of sigma-receptor ligands and metabolic PET tracers to 3 forms of chemotherapy: an in vitro study in glioma cells. J Nucl Med. 2006;47:1538–1545
  28. Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol. 1999;57:727–741
  29. Demidenko ZN, Halicka D, Kunicki J, McCubrey JA, Darzynkiewicz Z, Blagosklonny M. Selective killing of adriamycin-resistant (G2 checkpoint-deficient and MRP1-expressing) cancer cells by docetaxel. Cancer Res. 2005;65:4401–4407
  30. Direcks WGE, Berndsen SC, Proost N, Peters GJ, Balzarini J, Spreeuwenberg MD, et al. Molthoff CFM [(18)F]FDG and [(18)F]FLT uptake in human breast cancer cells in relation to the effects of chemotherapy: an in vitro study. Br J Cancer. 2008;99:481–487
  31. Rasey JS, Grierson JR, Wiens LW, Kolb PE. Uptake of labeled FLT correlates with thymidine kinase (TK1) activity in human tumor cells. J Nucl Med. 2000;41(Suppl 1):36P
  32. Demarcq C, Bastian G, Remvikos Y. BrdUrd/DNA flow cytometry analysis demonstrates cis-diamminedichloroplatinum (II)-induced multiple cell-cycle modifications on human lung carcinoma cells. Cytometry. 1992;13:416–422
  33. Kinsella AR, Smith D, Pickard M. Resistance to chemotherapeutic antimetabolites: a function of salvage pathway involvement and cellular response to DNA damage. Br J Cancer. 1997;75:935–945

PII: S0969-8051(08)00236-9

doi: 10.1016/j.nucmedbio.2008.10.012

Nuclear Medicine and Biology
Volume 36, Issue 2 , Pages 163-169 , February 2009