Species difference of astatine-211 uptakes in the whole body distribution: preclinical study using treated At-solution.

Objectives: Astatine-211 (²¹¹At) is halogen element which can be used for alpha-particle therapy. However, chemical form and dynamics in the body are not sufficiently elucidated because there is no stable isotope of astatine. We have recently shown the enhancement of ²¹¹At uptake in the thyroid by using the ²¹¹At solution treated with reducing agent possibly due to the fact that the chemical forms were unified. The purpose of this study was to evaluate the species difference of ²¹¹At uptakes in the whole body distribution using the treated ²¹¹At solution in which chemical form was unified. [Methods] Three male Wistar rats (n=3, body weight=285.9 ± 19.7g) and three nude mice (n=3, body weight=25.2 ± 1.7g) were investigated in this study. ²¹¹At solutions treated with ascorbic acid were injected through the tail vein under isoflurane anesthesia (2.72 ± 0.12 MBq in the rats and 0.90 ± 0.08 MBq in the mice). Planar images were acquired at 30 min, 3, 6, and 24 hrs after injection of ²¹¹At using E-Cam scanner (Siemens) targeting the X-rays emitted from the daughter nuclide of ²¹¹Po. Regions of interest were placed on the neck area, the stomach area and the bladder area using AMIDE software (Ver. 1.0.4). Radioactivity of the major organs were measured by gamma counter after euthanasia and dissection at 24 hrs. Uptakes were normalized by the injected dose (MBq) and body weight (g), and compared between the rats and the mice by Mann-Whitney U test. [Results] Planar images revealed that uptakes were peaked at 3-6 hrs post injection (%ID/g at 3hrs in the rats and the mice: 4.6 ± 2.6 vs 12.6 ± 8.3 in the neck area, 24.3 ± 0.2 vs 19.4 ± 3.4 in the stomach area, and 2.9 ± 2.5 vs 8.9 ± 6.7 in the bladder area, respectively). At 24 hrs after injection, the rats showed significantly higher uptakes in the thyroid gland (23,916 ± 12,110 vs 1,451 ± 232 CPM/Bq), the lung (47.5 ± 7.3 vs 14.4 ± 5.5), the liver (6.4 ± 0.2 vs 2.9 ± 0.6), the stomach (200.9 ± 28.0 vs 77.2 ± 13.0) and the spleen (77.7 ± 32.3 vs 2.4 ± 2.0), and significantly lower uptakes in the submandibular gland (9.6 ± 1.4 vs 167.0 ± 26.8) compared to the mice. No significant difference was observed in the kidney between the rats and the mice (16.3 ± 1.3 vs 19.3 ± 18.3). [Conclusion] There was still a large species difference of ²¹¹At uptakes between the rats and the mice using At solution treated with ascorbic acid. It was suggested that attention must be paid about the physiological accumulation of unlabeled ²¹¹At in non-target organs, such as the salivary gland, when we start the clinical trials of the targeted radionuclide therapy.

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