Evaluation of the specificity of [18F]fludarabine PET/CT in a xenograft model of follicular lymphoma: comparison with [18F]FDG and impact of rituximab therapy

Background: [F-18] Fludarabine is a novel positron emission tomography (PET) radiotracer for imaging lymphoma. The purpose of this preclinical study was to evaluate the robustness of [F-18] fludarabine during rituximab therapy. In addition, a comparison was made between [F-18] fludarabine and [F-18] fluorodeoxyglucose ([F-18] FDG) with regard to their concordance with histologically derived data. Methods: CB17-SCID mice bearing human follicular DOHH-2 lymphoma were treated once weekly with rituximab (10 mg/kg) or physiological saline over 3 weeks. To obtain the tracer uptake in the metabolically active volume of the tumour (MAVT), a background-level threshold was applied to the volume of interest (VOI) defined on computed tomography (CT) image. The tumour uptake analysis was performed with MAVT-based segmentation for data analysis of sequential [F-18] fludarabine PET/CT studies and with total tumour-based segmentation for comparison with histologically derived data. Results: The correlation between the MAVT and [F-18] fludarabine accumulation (% ID) in those viable tissues was equally significant for both vehicle-or rituximab-treated mice; for these latter, the presence of lymphoid tissues at the end of imaging sessions was confirmed histologically. A stronger correlation was demonstrated between quantitative values extracted from [F-18] fludarabine-PET and histology (r(2) = 0.91, p < 0.001) when compared to [F-18] FDG-PET (r(2) = 0.55, p = 0.03). Conclusions: [F-18] Fludarabine uptake in the follicular lymphoma model compared favourably with [F-18] FDG in terms of specificity for PET imaging and also remained robust for persistent viable tissues following rituximab therapy. [F-18] Fludarabine PET/CT may be a promising approach to evaluate lymphoma, including their surveillance during therapy.