Enhanced therapeutic effect with repeated administration of [211At]NaAt for differentiated thyroid cancer in mice

1256 Purpose: An alpha-emitter, astatine(211At), can be used for the targeted alpha therapy of differentiated thyroid cancer. We have shown the dose-dependent treatment effect of 211At-NaAt solution using K1-NIS xenograft mice by single intravenous administration. In this study, we evaluated the therapeutic effect of repeated administration of 211At-NaAt solution to achieve the better tumor growth control against the radiation-induced toxicity of for the clinical application. Methods: Total of 0.4MBq (n=9), 0.8MBq (twice administration of 0.4MBq, n=9) and 1.2MBq (triple administration of 0.4MBq, n=4) of 211At-NaAt solutions were injected into each group of K1-NIS (NIS-expressing human papillary thyroid cancer) xenograft mice. The interval between the administrations was 15 ± 2 days. Tumor size were followed by caliper measurement and compared. Tumor xenograft in mice were removed for frozen blocks nine days after the second administration of 211At-NaAt solution and immunohistochemical staining for NIS expression were performed and compared to control group (n=2). Results: Tumor growth was suppressed after single administration of 211At-NaAt, and extended the tumor regrowth with repeated dosing. NIS expression in tumor xenograft showed no significant change after the second administration of 211At-NaAt solution by immunohistochemistry, suggesting preserved NIS expression without the predominance of low-NIS expressing cells after administration of 211At-NaAt. Conclusions: This study showed effectiveness of multiple injection of 211At-NaAt in mice xenograft model, suggesting the feasibility of repeated administration in 211At-NaAt therapy for the differentiated thyroid cancer.Figure 1. Change in the tumor size after multiple-administration of 211At-NaAt solution.