Comparative Analysis between [18F]Fludarabine-PET and [18F]FDG-PET in a Murine Model of Inflammation

Lymphoma research has advanced thanks to introduction of [18F]­fludarabine, a positron-emitting tool. This novel radiotracer has been shown to display a great specificity for lymphoid tissues. However, in a benign process such as inflammation, the uptake of this tracer has not been questioned. Indeed, in inflammatory zones, elevated glucose metabolism rate may result in false-positives with [18F]­FDG-PET Imaging. In the present investigation, it has been argued that cells, involved in inflammation, might be less avid of [18F]­fludarabine. To generate inflammation, Swiss mice were intramuscularly injected with 0.1 mL of turpentine oil into the right front paw. Imaging sessions with 18F-labeled tracers named above were conducted on days 5 and 25 after inoculation. For each animal, volumes of interest (VOI), delineating the muscle of the inflamed (IP) and normal paws (NP), were determined on PET scans. For characterization of inflammation, muscle samples from IP and NP were stained with hematoxylin and eosin (H&E). In early (day 5) inflammation, [18F]­FDG accumulation was 4.00 ± 1.65 times greater in the IP than in the contralateral NP; for [18F]­fludarabine, this IP/NP ratio was 1.31 ± 0.28, resulting in a significant difference between radiotracer groups (p < 0.01). In late (day 25) inflammation, the IP/NP ratios were 2.07 ± 0.49 and 1.03 ± 0.07, for [18F]­FDG and [18F]­fludarabine, respectively (p < 0.001). [18F]­Fludarabine showed significantly weaker uptake in inflammation when compared with [18F]­FDG. This encouraging finding suggests that [18F]­fludarabine-PET might well be a robust approach for distinguishing tumor from inflammatory tissue, avoiding false-positive PET results and thus enabling an accurate imaging of lymphoma.