89Zr-Bevacizumab PET: Potential Early Indicator of Everolimus Efficacy in Patients with Metastatic Renal Cell Carcinoma

Currently, biomarkers that predict the efficacy of everolimus in metastatic renal cell carcinoma (mRCC) patients are lacking. Everolimus inhibits vascular endothelial growth factor A (VEGF-A) expression. We performed PET scans on mRCC patients with Zr-89-bevacizumab, a VEGF-A-binding antibody tracer. The aims were to determine a change in tumor tracer uptake after the start of everolimus and to explore whether Zr-89-bevacizumab PET can identify patients with early disease progression. Methods: Zr-89-bevacizumab PET was done before and 2 and 6 wk after the start of everolimus, 10 mg/d, in mRCC patients. Routine CT scans were performed at baseline and every 3 mo thereafter. Tumor tracer uptake was quantified using SUVmax. The endpoints were a change in tumor tracer uptake and treatment response on CT after 3 mo. Results: Thirteen patients participated. The median SUVmax of 94 tumor lesions was 7.3(range, 1.6-59.5). Between patients, median tumor SUVmax varied up to 8-fold. After 2 wk, median SUVmax was 6.3 (1.7-62.3), corresponding to a mean decrease of 9.1% (P < 0.0001). Three patients discontinued everolimus early. At 6 wk, a mean decrease in SUVmax of 23.4% compared with baseline was found in 70 evaluable lesions of 10 patients, with a median SUVmax of 5.4 (1.1-49.4, P < 0.0001). All 10 patients who continued treatment had stable disease at 3 mo. Conclusion: Everolimus decreases Zr-89-bevacizumab tumor uptake. Further studies are warranted to evaluate the predictive value of Zr-89-bevacizumab PET for everolimus antitumor efficacy.