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

Purpose The aim of this study was to determine whether the thymidine analogue 3'-deoxy-3'-[F-18] 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 ([Y-90] CD20 mAb, Zevalin, n=10). Forty-eight hours after treatment, antiproliferative effects were assessed with [F-18] FLT. Ninety minutes after i.v. injection of 5-10 MBq [F-18] 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 radio-immunotherapy to 78.8% (p=0.014). In none of the animals was a significant change in tumour size observed. In untreated lymphoma, tumoural [F-18] 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 [F-18]FLT-PET for imaging early response to treatment in malignant lymphoma.