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

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

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Published in:European journal of nuclear medicine and molecular imaging 2007-11, Vol.34 (11), p.1775-1782
Main Authors: Buck, Andreas K, Kratochwil, Clemens, Glatting, Gerhard, Juweid, Malik, Bommer, Martin, Tepsic, Djurdja, Vogg, Andreas T J, Mattfeldt, Torsten, Neumaier, Bernd, Möller, Peter, Reske, Sven N
Format: Article
Language:English
Subjects:
Animals
Chemotherapy
Dideoxynucleosides - pharmacokinetics
Humans
Lymphoma
Lymphoma - diagnostic imaging
Lymphoma - metabolism
Lymphoma - therapy
Medical imaging
Medical tests
Mice
Nuclear medicine
Radionuclide Imaging
Radiopharmaceuticals - pharmacokinetics
Rodents
Treatment Outcome
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Summary:The aim of this study was to determine whether the thymidine analogue 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) is adequate for early evaluation of the response of malignant lymphoma to antiproliferative treatment in a mouse xenotransplant model. 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 ([(90)Y]CD20 mAb, Zevalin, n = 10). Forty-eight hours after treatment, antiproliferative effects were assessed with [(18)F]FLT. Ninety minutes after i.v. injection of 5-10 MBq [(18)F]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. 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 [(18)F]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). In a lymphoma xenotransplant model, [(18)F]FLT detects early antiproliferative drug activity before changes in tumour size are visible. These findings further support the use of [(18)F]FLT-PET for imaging early response to treatment in malignant lymphoma.
ISSN:1619-7070
1619-7089
DOI:10.1007/s00259-007-0452-z