Abstract 4049: Early prediction of response to targeted drugs treatment in malignant lymphoma and sarcoma using in vivo proliferation marker 18F-FLT

Abstract

Purpose: Last year we have shown that 18F-FLT is superior surrogate marker than 18F-FDG for very early response assessment to therapy in malignant Lymphoma. In this study, we use FLT-PET to predict the response of ewing sarcoma to different cancer therapy and investigate its relation to cancer cell death, especially apoptosis. Methods: FLT and/ or FDG PET were performed prior and early in each therapeutic course on SCID mice bearing with various tumor cells. Ewing sarcoma A673 was applied for investigation of the response to sorafenib treatment or Radiotherapy. GFP labelled Lymphoma cells (Myc449, Myc665) with or without transportation of Bcl2 gene was employed for the observation of cell death especially apoptosis after the treatment with aura kinase inhibitor or chemotherapy. Tumor-to-background ratios (TBR) of FLT-PET were compared to that of FDG-PET. PET findings were correlated with optical Imaging, histopathology and in vitro data comprising cellular tracer uptake, cell cycle related protein expression, cell cycle distribution and viability assessment. Results: In vitro study shows that sarcoma A673 cells were sensitive to all therapy. For in vivo studies, tumor volume of sorafenib treated animals showed modest increase of 0.1cm3 (range 0.02cm3 to 0.2cm3, SD=0.09) within the first week as opposed to a 15-fold increase in control mice. Median TBR of FLT-PET decreased significantly to 30.1% compared to baseline as early as 5d after therapy (range 11.3-53.5%, n=12, p=0.0004). On the other side, TBR in FDG-PET also showed the similar tendency (median TBR 74.6%, range 28.1%-131.8%, n=12, p=0.02). But the reduction of TBR in FLT was significantly stronger than that in FDG (p<0.001). In vitro study of lymphoma cells with Bcl2 transduction showed a strong anti- cell death ability, which will be served for the link between FLT PET and cell death. Conclusion: Compared with FDG-PET, FLT-PET is able to predict the response in the early therapeutic course and has a high specificity for the detection of ewing sarcoma. Continuing studies are intensively carried out to investigate FLT and FDG PET in relation to therapy-induced cell death. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4049. doi:1538-7445.AM2012-4049