336 Sorafenib Decreases Indium-111-girentuximab Tumor Uptake in Clear Cell Renal Cell Carcinoma Patients

No. 27 Objectives A new approach in the treatment of clear cell renal cell carcinoma (ccRCC) is radioimmunotherapy (RIT) using chimeric anti-carbonic anhydrase IX (CAIX) antibody girentuximab (cG250). Now results of phase I RIT trials become available, the question arises which sequence is optimal when combining RIT with tyrosine kinase inhibitors (TKI). In this study, we assessed the effect of the widely used TKI sorafenib on the tumor uptake of In-111-cG250. Methods In-111-cG250 scanning was performed in 14 patients with primary renal tumors planned for surgery. Four patients were treated with sorafenib in a neoadjuvant setting for 1 week, and five patients for 4 weeks. In the sorafenib-treated groups, baseline and posttreatment scans were compared. The remaining five patients had one scan without any pre-operative treatment. A 1-cm slice of the surgical specimen was scanned to assess the intratumoral distribution of In-111-cG250. Expression of CAIX and of vascular marker CD31 was determined by immunohistochemistry. Results 12 of 14 patients had ccRCC. In all of these 12, the lesions were clearly identified with In-111-cG250 scintigraphy. Treatment with sorafenib resulted in a significant decrease of In-111-cG250 uptake in ccRCC lesions (1 week: mean change -30.6%; range +3.1% to -60.6%, 4 weeks: mean change -56.5%; range -32.6% to -79.7%). CAIX expression was similar in all three groups and was not affected by sorafenib treatment. A major reduction of tumor vessels was observed in the specimens obtained after sorafenib treatment. Conclusions In-111-cG250 accumulates efficiently in ccRCC lesions. Treatment with sorafenib resulted in a significantly decreased targeting of In-111-cG250 to ccRCC lesions. These results indicate that RIT should not be applied during TKI treatment