89Zr-Bevacizumab PET Visualizes Heterogeneous Tracer Accumulation in Tumor Lesions of Renal Cell Carcinoma Patients and Differential Effects of Antiangiogenic Treatment

S. F. Oosting, A. H. Brouwers, S. C. van Es, W. B. Nagengast, T. H. Oude Munnink, M. N. Lub-de Hooge, H. Hollema, J. R. de Jong, I. J. de Jong, S. de Haas, S. J. Scherer, W. J. Sluiter (+4 others)
2014 Journal of Nuclear Medicine  
No validated predictive biomarkers for antiangiogenic treatment of metastatic renal cell carcinoma (mRCC) exist. Tumor vascular endothelial growth factor A (VEGF-A) level may be useful. We determined tumor uptake of 89 Zr-bevacizumab, a VEGF-A-binding PET tracer, in mRCC patients before and during antiangiogenic treatment in a pilot study. Methods: Patients underwent 89 Zrbevacizumab PET scans at baseline and 2 and 6 wk after initiating either bevacizumab (10 mg/kg every 2 wk) with interferon-α
more » ... (3-9 million IU 3 times/wk) (n 5 11) or sunitinib (50 mg daily, 4 of every 6 wk) (n 5 11). Standardized uptake values were compared with plasma VEGF-A and time to disease progression. Results: 89 Zrbevacizumab PET scans visualized 125 evaluable tumor lesions in 22 patients, with a median SUV max (maximum standardized uptake value) of 6.9 (range, 2.3-46.9). Bevacizumab/interferon-α induced a mean change in tumor SUV max of −47.0% (range, −84.7 to 120.0%; P , 0.0001) at 2 wk and an additional −9.7% (range, −44.8 to 138.9%; P 5 0.015) at 6 wk. In the sunitinib group, the mean change in tumor SUV max was −14.3% at 2 wk (range, −80.4 to 1269.9; P 5 0.006), but at 6 wk the mean change in tumor SUV max was 172.6% (range, −46.4 to 1236%; P , 0.0001) above baseline. SUV max was not related to plasma VEGF-A at all scan moments. A baseline mean tumor SUV max greater than 10.0 in the 3 most intense lesions corresponded with longer time to disease progression (89.7 vs. 23.0 wk; hazard ratio, 0.22; 95% confidence interval, 0.05-1.00). Conclusion: Tumor uptake of 89 Zr-bevacizumab is high in mRCC, with remarkable interpatient and intrapatient heterogeneity. Bevacizumab/interferon-α strongly decreases tumor uptake whereas sunitinib results in a modest reduction with an overshoot after 2 drugfree weeks. High baseline tumor SUV max was associated with longer time to progression.
doi:10.2967/jnumed.114.144840 pmid:25476536 fatcat:f57ajwj6pzgmblls2nt2fmqexy