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Early assessment of therapy response in malignant lymphoma with the thymidine analogue [18F]FLT

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to determine whether the thymidine analogue 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) is adequate for early evaluation of the response of malignant lymphoma to antiproliferative treatment in a mouse xenotransplant model.

Methods

Immunodeficient mice bearing a follicular lymphoma xenotransplant were treated with high-dose chemotherapy (cyclophosphamide, n = 10), immunotherapy (CD20 mAb, ibritumomab-tiuxetan, n = 10) or radioimmunotherapy ([90Y]CD20 mAb, Zevalin, n = 10). Forty-eight hours after treatment, antiproliferative effects were assessed with [18F]FLT. Ninety minutes after i.v. injection of 5–10 MBq [18F]FLT, mice were sacrificed and radioactivity within the tumour and normal organs was measured using a gamma counter and calculated as % ID/g. The proliferation fraction in tissue samples derived from treated and untreated tumours was evaluated by Ki-67 immunohistochemistry, which served as the reference for proliferative activity.

Results

In untreated lymphoma, the mean proliferation fraction was 83.6%. After chemotherapy, the mean proliferation fraction decreased to 39.3% (p = 0.0001), after immunotherapy to 77.6% (p = 0.0078) and after radioimmunotherapy to 78.8% (p = 0.014). In none of the animals was a significant change in tumour size observed. In untreated lymphoma, tumoural [18F]FLT uptake was 5.4% ID/g, after chemotherapy it was 1.5% (p = 0.0005), after immunotherapy, 3.9% (non-significant), and after radioimmunotherapy, 5.8% (non-significant).

Conclusion

In a lymphoma xenotransplant model, [18F]FLT detects early antiproliferative drug activity before changes in tumour size are visible. These findings further support the use of [18F]FLT-PET for imaging early response to treatment in malignant lymphoma.

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Acknowledgements

This work was in part supported by grant Bu 1424/1 from Deutsche Forschungsgemeinschaft (DFG, KFO 120) and grant P.777 (Medical Faculty, University of Ulm). We thank Rolf Kunft for his assistance in digital microscopy. We also thank Gabi Ehmke for performing immunohistochemistry and Robert Stadler for his helpful comments on the manuscript.

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Authors and Affiliations

  1. Department of Nuclear Medicine, University Hospital Ulm, Ulm, Germany

    Andreas K. Buck, Clemens Kratochwil, Gerhard Glatting, Djurdja Tepsic, Andreas T. J. Vogg, Bernd Neumaier & Sven N. Reske

  2. Department of Haematology, University Hospital Ulm, Ulm, Germany

    Martin Bommer

  3. Institute of Pathology, University Hospital Ulm, Ulm, Germany

    Torsten Mattfeldt & Peter Möller

  4. Department of Nuclear Medicine, Technical University Munich, Ismaninger Strasse 22, 81675, Munich, Germany

    Andreas K. Buck

  5. Department of Radiology and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA

    Malik Juweid

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  1. Andreas K. Buck
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Correspondence to Andreas K. Buck.

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Buck, A.K., Kratochwil, C., Glatting, G. et al. Early assessment of therapy response in malignant lymphoma with the thymidine analogue [18F]FLT. Eur J Nucl Med Mol Imaging 34, 1775–1782 (2007). https://doi.org/10.1007/s00259-007-0452-z

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