89Zr-bevacizumab PET shows heterogeneous tracer accumulation in tumor lesions of Renal Cell Carcinoma and varying effects of anti-angiogenic treatment

Currently, no validated predictive biomarkers exist for anti-angiogenic treatment of metastatic renal cell carcinoma (mRCC). Yet, it is believed that tumor vascular endothelial growth factor A (VEGF-A) level may be useful. This way, in a pilot study [1] researchers have determined the tumor uptake of 89Zr-bevacizumab, a VEGF-A-binding PET tracer, in mRCC patients before and during anti-angiogenic treatment.

Patients were subjected to 89Zr-bevacizumab PET scans at baseline and 2 and 6 weeks after initiating treatment with either bevacizumab plus interferon-α, or sunitinib. Standardized uptake values (SUV) were compared to plasma VEGF-A and time to disease progression.
89Zr-bevacizumab PET scans enabled the visualization of 125 evaluable tumor lesions in 22 patients (median SUVmax: 6.9). Bevacizumab/interferon-α induced a mean change in tumor SUVmax of -47.0% at 2 weeks, and an additional -9.7% at 6 weeks. The sunitinib group presented a mean change in tumor SUVmax of -14.3% at 2 weeks, but at 6 weeks this mean change was of +72.6% above baseline. However, SUVmax was not related to plasma VEGF-A at all scan moments. Still, a baseline mean tumor SUVmax > 10.0 in the three most intense lesions corresponded with longer time to disease progression (89.7 versus 23.0 weeks).
These results show that tumor uptake of 89Zr-bevacizumab is high in mRCC, with great inter- and intra-patient heterogeneity. Bevacizumab/interferon-α strongly decreases tumor uptake, whereas sunitinib results in a modest reduction with an overshoot after two drug-free weeks. In addition, high baseline tumor SUVmax was associated with longer time to progression.
In conclusion, 89Zr-bevacizumab PET showed to be a reliable tool for assessing tumor uptake rate in mRCC, and therefore predicting the treatment success in this disease.

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 [1] Oosting SF, Brouwers, AH, van Es SC, Nagengast WB, Oude Munnink TH, Lub-de Hooge MN, Hollema H, de Jong JR, de Jong IJ, de Haas S, Scherer SJ, Sluiter WJ, Dierckx RA, Bongaerts AH, Gietema JA, de Vries EG. 89Zr-bevacizumab PET Visualizes Heterogeneous Tracer Accumulation in Tumor Lesions of Renal Cell Carcinoma Patients and Differential Effects of Anti-angiogenic Treatment. J Nucl Med. 2014 Dec 4 [Epub ahead of print]. PMID: 25476536.