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

Journal of Nuclear Medicine

Wim J.G. Oyen¹  Egbert Oosterwijk¹  Carla M.L. van Herpen¹  Alexander B. Stillebroer¹  William P.J. Leenders¹  Winette T.A. van der Graaf¹  Peter F.A. Mulders¹  Otto C. Boerman¹  Ingrid M.E. Desar¹ 

关键词: ¹¹¹In-bevacizumab scintigraphy;    renal cell carcinoma;    sorafenib;    angiogenesis inhibitor;    biomarker;   

DOI  :  10.2967/jnumed.110.078030

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 111In-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 111In-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 111In-bevacizumab scans were compared. The intratumoral distribution of 111In-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, α-smooth-muscle actin, and Ki67 was determined by immunohistochemistry and compared with the local concentration of 111In-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 111In-bevacizumab was observed in the tumors. All ccRCC lesions with enhanced 111In-bevacizumab targeting expressed high levels of VEGF-A. Treatment with sorafenib resulted in a significant decrease of 111In-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 111In-bevacizumab scintigraphy. Neoadjuvant treatment with sorafenib resulted in a significant decrease of 111In-bevacizumab uptake in RCC. 111In-bevacizumab scintigraphy can be an attractive biomarker for response and needs further study.

【 授权许可】

Unknown