Monitoring Lutetium-177-anti-CAIX radioimmunotherapy with In-111-anti-CAIX SPECT in an intraperitoneal clear cell renal cell carcinoma xenograft model

Objectives Radioimmunotherapy (RIT) with radiolabeled anti-carbonic anhydrase IX (CAIX) antibody G250 is a new approach in the treatment of clear cell renal cell carcinoma (ccRCC). Potentially the efficacy of Lu-177-anti CAIX RIT can be monitored with In-111-anti-CAIX SPECT. Here the potential of this theranostics approach was studied in mice with intraperitoneal ccRCC.

Methods Mice with intraperitoneally growing SK-RC-52 tumor lesions (3 weeks after tumor cell inoculation) were treated with 13 MBq Lu-177-G250 (n=10), a control group received 13 MBq Lu-177-labeled irrelevant antibody MOPC21 (n=10) and the second control group was not treated. Tumor growth in the three groups was monitored with SPECT/CT with In-111-G250 at 3 week intervals. Primary endpoints were overall survival and toxicity.

Results The optimal G250 protein dose to target ccRCC in this model was 10 μg G250. Tumor uptake 48 h p.i. was 54.9±3.5 % ID/g, with a tumor-to-blood ratio of 5.3:1. The median survival of the mice in the control groups was 53 days after inoculation, whereas treatment with Lu-177-G250 resulted median survival of >100 days. Survival was significantly longer in the group treated with Lu-177-G250 (log-rank test, p=0.002). Tumor progression over time could be monitored noninvasively with SPECT.

Conclusions This is the first RIT study with radiolabeled G250 in mice with i.p. growing ccRCC. The optimal dose for in vivo targeting and monitoring of ccRCC in this model was 10 μg/mouse. RIT with Lu-177-G250 significantly improved median survival. This model is suitable to further investigate the potential of RIT of ccRCC.