Increased Uptake of At-211 in Thyroid Gland by the Preparation with Ascorbic Acid for Targeted Alpha Therapy of Thyroid Cancer

Abstract

Astatine-211 (211At) is an alpha-emitting radionuclide suitable for targeted alpha therapy. Because At is a heavier homolog of iodine, astatide ion (At-) is expected to be applied to the treatment of thyroid cancer. In this study, 211At was treated by ascorbic acid (AA) as reducing agent to prepare At-. We aimed to evaluate the uptake change in the thyroid after the preparation of 211At solutions with AA and demonstrate the treatment effect in the differentiated thyroid cancer xenograft mice. Astatine-211 was produced in the 209Bi(α, 2n) reaction and supplied through Shortlived RI Supply Platform. Produced 211At was then separated from the target materials by a dry distillation method and dissolved in pure water. The aliquot of 211At solution was mixed with 1% AA solution to prepare At-. The radiochemical yield was checked by radio-TLC. The crude 211At solution or 211At with AA solution was administered to normal rats (n=3 for both solution) through tail vein under isoflurane anesthesia. In vivo imaging of 211At in the normal rats was then carried out using a gamma camera at 0.5, 3, 6 and 24 hrs after administration. The 211At solution with AA was also administered to mice with implanted K1 cells (human papillary thyroid carcinoma) expressing sodium iodide symporter (NIS). Mice were divided into 4 groups according to the injected dose [1 MBq (n=6), 0.4 MBq (n=6), 0.1 MBq (n=6), control (n=6)]. Distribution of 211At administered in the mice was investigated at 3 and 24 hrs after administration by the gamma camera. The radiochemical yield of At- checked by radio-TLC increased from approximately 20% to 90% after treatment of the crude 211At solution with AA. In vivo imaging of 211At in the normal rats showed high uptakes in the thyroid, the stomach, and the bladder. Uptake of At with AA in thyroid gland was 2–3 times higher compared to crude 211At solution. In the xenograft mice, there was a stable accumulation in the thyroid tumor at 3 and 24 hrs post administration (23 ± 11 %ID and 13 ± 7 %ID, respectively). Tumor growth was immediately inhibited after administration of 211At in a dose-dependent manner. Suppression of tumor growth was maintained until 17, 31, and 41 days after administration of 211At in 0.1, 0.4, and 1 MBq groups, respectively. Uptake of 211At can be enhanced in the normal thyroid by increasing the radiochemical purity of At-. The administered 211At showed good treatment effect in thyroid cancer xenograft, suggesting that 211At solution with AA is promising for the targeted alpha therapy for the thyroid cancer.