Comparison and evaluation of [18F]FDG and [18F]FLT response in B-cell lymphoma mice treated with cytotoxic or antiproliferative agents

Objectives Shortly after treatment the influx of inflammatory cells can interfere with [18F]FDG uptake while [18F]FLT is less affected by this phenomenon. In this study [18F]FDG and [18F]FLT uptake was monitored after cytotoxic or antiproliferative therapy and correlated to the number of viable cells assessed with bioluminescence imaging (BLI).

Methods Daudi cells (Burkitt lymphoma) were transduced with a lentiviral vector (blasticidin selection marker and firefly luciferase reporter gene) and inoculated in SCID-mice (n=57). Mice were treated with Endoxan (125mg/kg, n=25) or Torisel (50mg/kg, n=25). [18F]FDG and [18F]FLT µPET and BLI were performed on days 0, 2, 4, 7, 9, 11 (no [18F]FLT) and 14. Histology was performed using H&E, TUNEL and Ki-67.

Results Endoxan reduced [18F]FDG uptake from d2 without a significant reduction in [18F]FLT (only reduced from d7). BLI showed an increased signal on d2 and d4 while a reduction in the number of viable cells was measured from d7. Torisel treatment reduced [18F]FDG and [18F]FLT uptake from d2 after therapy. Reduction of [18F]FLT uptake was maximal on d4 versus d9 for [18F]FDG. BLI showed the same early signal increase as after Endoxan and a reduced number of viable cells was observed from d7 on. Proliferation (Ki-67) decreased only late after Endoxan treatment (d9-d14) while the decrease was faster (d2, d4) after Torisel treatment in line with the [18F]FLT response. In both treatment groups an increase in apoptotic and necrotic tumor fraction was measured. Further histological evaluation is underway to explore the rise in BLI signal, the role of inflammation and DNA repair early after therapy.

Conclusions In conclusion, [18F]FLT-µPET was able to detect the reduced proliferation following therapy. After cytotoxic treatment [18F]FDG could predict response earlier than [18F]FLT