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Imaging proliferation in vivo with [F-18]FLT and positron emission tomography

Nature Medicine volume 4, pages 1334–1336 (1998)Cite this article

Abstract

Positron emission tomography (PET) is now regularly used in the diagnosis and staging of cancer. These uses and its ability to monitor treatment response would be aided by the development of imaging agents that can be used to measure tissue and tumor proliferation. We have developed and tested [F-18]FLT (3'-deoxy-3'-fluorothymidine); it is resistant to degradation, is retained in proliferating tissues by the action of thymidine kinase 1 (TK), and produces high-contrast images of normal marrow and tumors in canine and human subjects.

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Figure 1: Structure of FLT and its phosphorylation by thymidine kinase 1 (TK1).
Figure 2: a, Whole-body image obtained with 81 MBq [F-18]FLT (after the dynamic imaging was completed).
Figure 3: FLT image of the neck of a dog with non-Hodgkin's lymphoma in two enlarged nodes (open arrows) and marrow activity (filled arrow) as well.
Figure 4: Images of a patient with non-small cell lung cancer obtained after the injection of 50 MBq of [F-18]FLT using a GE Advance tomograph (Milwaukee, Wisconsin).

References

  1. Shields, A.F., Graham, M.M. & Spence, A.M. The role of PET imaging in clinical oncology: A current status report. Nuclear Med. Annual 129–168 (1995).

  2. Herholz, K., Rudolf, J. & Heiss, W.D. FDG transport and phosphorylation in human gliomas measured with dynamic PET. J. Neurooncol. 12, 159–165 (1992).

    Article  CAS  Google Scholar 

  3. Findlay, M. et al. Noninvasive monitoring of tumor metabolism using fluorodeoxyglucose and positron emission tomography in colorectal cancer liver metastases: Correlation with tumor response to fluorouracil. J. Clin. Oncol. 14, 700–708 (1996).

    Article  CAS  Google Scholar 

  4. Shields, A. et al. [11C]Thymidine and FDG to measure therapy response. J. Nucl. Med. (in the press).

  5. Romer, W. et al. Positron emission tomography in non-Hodgkin's lymphoma: Assessment of chemotherapy with fluorodeoxyglucose. Blood 91, 4464–4471 (1998).

    CAS  PubMed  Google Scholar 

  6. Kubota, R. et al. Intratumoral distribution of 18F-fluorodeoxyglucose in vivo: High accumulation in macrophages and granulation tissues studied by microautoradiography. J. Nucl. Med. 33, 1972–1980 (1992).

    CAS  PubMed  Google Scholar 

  7. Yamada, Y. et al. Fluorine-18-fluorodeoxyglucose and carbon-11-methionine evaluation of lymphadenopathy in sarcoidosis. J. Nucl. Med. 39, 1160–1166 (1998).

    CAS  PubMed  Google Scholar 

  8. van Eijkeren, M.E. et al. Kinetics of [methyl-11C]thymidine in patients with squamous cell carcinoma of the head and neck. Acta Oncol. 35, 737–741 (1996).

  9. Vander Borght, T., Labar, D., Pauwels, S. & Lambotte, L. Production of [2-11C]thymidine for quantification of cellular proliferation with PET. Appl. Radiat. Isot. 42, 103–104 (1991).

    Article  CAS  Google Scholar 

  10. Conti, P., Alauddin, M., Fissekis, J., Schmall, B. & Watanabe, K. 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. 22, 783–789 (1995).

    Article  CAS  Google Scholar 

  11. Grierson, J.R., Shields, A.F. & Courter, J.H. Radiosynthesis of 2'-deoxy-1-[C-11]methyl-pseudouridine, an Isostere of labeled thymidine, as an agent for the measurement of DNA synthesis in vivo. J. Labelled Compounds Radiopharm. 35, 290–291 (1994).

    Google Scholar 

  12. Shields, A.F., Grierson, J.R., Kozawa, S.M. & Zheng, M. Development of labeled thymidine analogs for imaging tumor proliferation. Nucl. Med. Biol. 23, 17–22 (1996).

    Article  CAS  Google Scholar 

  13. Flexner, C. et al. Relationship between plasma concentrations of 3'-deoxy-3'- fluorothymidine (alovudine) and antiretroviral activity in two concentration-controlled trials. J. Infect. Dis. 170, 1394–1403 (1994).

    Article  CAS  Google Scholar 

  14. Kong, X.B. 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. 36, 808–818 (1992).

    Article  CAS  Google Scholar 

  15. Sherley, J.L. & Kelly, T.J. Regulation of human thymidine kinase during the cell cycle. J. Biol. Chem. 263, 8350–8358 (1988).

    CAS  PubMed  Google Scholar 

  16. Grierson, J.R., Shields, A.F. & Eary, J.F. Development of a radiosynthesis for 3'-[F-18]fluoro-3'-deoxynucleosides. J. Labelled Compounds Radiopharm. 40, 60–62 (1997).

    Google Scholar 

  17. Sokoloff, L. et al. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: Theory, procedure, and normal values in the conscious and anesthetized albino rat. J. Neurochem. 28, 897–916 (1977).

    Article  CAS  Google Scholar 

  18. Nicolas, F. et al. Comparative metabolism of 3'-azido-3'-deoxythymidine in cultured hepatocytes from rats, dogs, monkeys, and humans. Drug Metab. Disposition 23, 308–313 (1995).

    CAS  Google Scholar 

  19. Tjuvajev, J.G. et al. Imaging of brain tumor proliferative activity with Iodine-131-iododeoxyuridine. J. Nucl. Med. 35, 1407–1417 (1994).

    CAS  PubMed  Google Scholar 

  20. Crawford, E.J. et al. 18F-5-fluorouridine, a new probe for measuring the proliferation of tissue in vivo. Adv. Enzyme Regul. 20, 3–22 (1982).

    Article  Google Scholar 

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Acknowledgements

This work was supported in part by Grant CA 39566 from the National Cancer Institute.

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Authors and Affiliations

  1. Departments of Medicine and Radiology, Karmanos Cancer Institute, Wayne State University, Detroit Medical Center, 5 Hudson, 3990 John R Street, Detroit, 48301, MI, USA

    Anthony F. Shields, Joseph C. Stayanoff, Jawana M. Lawhorn-Crews, Otto Muzik & Thomas J. Mangner

  2. Department of Radiology, Imaging Research Laboratory, University of Washington, Seattle, WA, USA

    John R. Grierson

  3. Department of Nuclear Medicine, Eberhard-Karls-University, Tuebingen, Germany

    Bernhard M. Dohmen & H.-Juergen Machulla

  4. Oakland Veterinary Referral Services, Bloomfield Hills, MI, USA

    Joyce E. Obradovich

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  1. Anthony F. Shields
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Correspondence to Anthony F. Shields.

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Shields, A., Grierson, J., Dohmen, B. et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med 4, 1334–1336 (1998). https://doi.org/10.1038/3337

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