TU‐A‐WAB‐01: Characterization of Vascular and Proliferative Flare in Anti‐Angiogenic Therapy Using FLT PET/CT and Circulating VEGF

Purpose: Previous studies observed significant rebound of tumor proliferation and vascularization following cessation of anti‐angiogenic therapy. In this study we characterize this phenomenon in a novel anti‐angiogenic agent, using both [18‐F]FLT PET/CT and circulating VEGF. Methods: Seventeen patients with solid tumors of various histologies were treated for two weeks with Axitinib, a molecularly targeted anti‐proliferative and anti‐angiogenic agent, 5mg twice daily, followed by a one‐week treatment break. Dynamic FLT PET scans were acquired at peak drug concentration (day 12–14), and washout (day 20–21). Vasculature status was quantified using a two‐compartment kinetic model (blood volume, Vb; blood‐to‐tissue transfer constant, K1). Proliferation was quantified using both kinetic analysis (net uptake rate, Ki) and SUV‐based metrics (SUVmean, SUVmax, SUVpeak, SUVtotal). Relative change in each of these metrics during washout was assessed. Blood samples obtained pre‐treatment and at each imaging time point were analyzed for the pro‐angiogenic factor VEGF (vascular endothelial growth factor). The change in VEGF during therapy was also assessed. Results: Seven of seventeen patients showed unambiguous proliferative flare, with all four SUV metrics increasing >20% during washout. Median increases of 30% SUVmean, 50% SUVmax, 60% SUVpeak, 70% SUVtotal, and 75% Ki were observed in these patients. Increase in vascular parameters were also observed in these patients (medians 30% Vb, 80% K1). Vascular and proliferative flare were correlated across all seventeen patients (ΔSUVpeak vs. ΔK1, R = 0.59). A highly significant increase in circulating VEGF (p