111In-Bevacizumab Imaging of Renal Cell Cancer and Evaluation of Neoadjuvant Treatment with the Vascular Endothelial Growth Factor Receptor Inhibitor Sorafenib

Clear cell renal cell cancer (ccRCC) prominently expresses vascular endothelial growth factor-A (VEGF-A), and new treatment strategies for renal cell cancer (RCC) aim at the inhibition of VEGF VEGF receptor signaling. This study explores the ability of In-111-bevacizumab scintigraphy to depict RCC and to evaluate response to neoadjuvant treatment with sorafenib, a VEGF receptor inhibitor. Methods: The ability to depict RCC with In-111-bevacizumab scintigraphy was tested in 14 patients scheduled to undergo a tumor nephrectomy; of these, 9 RCC patients were treated in a neoadjuvant setting with sorafenib (400 mg orally twice a day). In the latter group, baseline and posttreatment In-111-bevacizumab scans were compared. The intratumoral distribution of In-111-bevacizumab was determined scintigraphically ex vivo in a 1-cm lamella of the resected tumorous kidney. Expression of VEGF-A, glucose transporter-1, carbonic anhydrase IX, alpha-smooth-muscle actin, and Ki67 was determined by immunohistochemistry and compared with the local concentration of In-111-bevacizumab. Additionally, the VEGF-A content in tumor samples was determined quantitatively by enzyme-linked immunosorbent assay. Results: In all 5 non-neoadjuvant-treated patients, preferential accumulation of In-111-bevacizumab was observed in the tumors. All ccRCC lesions with enhanced In-111-bevacizumab targeting expressed high levels of VEGF-A. Treatment with sorafenib resulted in a significant decrease of In-111-bevacizumab uptake in the tumor in the patients with ccRCC (mean change, -60.5%; range, +1.5% to -90.1%). The decrease in uptake was due to destruction of the tumor neovasculature, whereas the VEGF-A expression remained intact. In the patient with papillary RCC, limited uptake without change after sorafenib was observed. Conclusion: RCC lesions were clearly delineated with In-111-bevacizumab scintigraphy. Neoadjuvant treatment with sorafenib resulted in a significant decrease of In-111-bevacizumab uptake in RCC. In-111-bevacizumab scintigraphy can be an attractive biomarker for response and needs further study.