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Characterization of Vascular and Proliferative Flare in Anti-Angiogenic Therapy Using FLT PET/CT and Circulating VEGF

P Scully

P Scully1*, G Liu1, U Simoncic2, R Jeraj1,2, (1) University of Wisconsin, Madison, WI (2) Institut Jozef Stefan, Ljubljana, Slovenia

TU-A-WAB-1 Tuesday 8:00AM - 9:55AM Room: Wabash Ballroom

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<0.001) occurs during the treatment period, followed by a highly significant drop (p<0.001) during the withdrawal period, to a level indistinguishable from baseline (p=0.9).

Conclusion: Substantial proliferative and vascular flare were observed in many patients during Axitinib withdrawal. These phenomena were correlated, suggesting Axitinib withdrawal may open a window for effective combination therapy. Axitinib treatment strongly impacts VEGF expression levels, suggesting it successfully targets the VEGF receptor.

Funding Support, Disclosures, and Conflict of Interest: Research funded in part by the U.W. Radiological Sciences Training Grant: 5T32CA009206-34 Research funded in part by Pfizer.

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