¹³¹ I is widely used for therapy in the clinic and ¹²⁵ I and ¹³¹ I, and increasingly ²¹¹ At, are often used in experimental studies. It is important to know the biodistribution and dosimetry for these radionuclides to determine potential risk organs when using radiopharmaceuticals containing these radionuclides. The purpose of this study was to investigate the biodistribution of ¹²⁵ I ⁻ , ¹³¹ I ⁻ , and free ²¹¹ At in rats and to determine absorbed doses to various organs and tissues. Male Sprague Dawley rats were injected simultaneously with 0.1–0.3 MBq ¹²⁵ I ⁻ and 0.1–0.3 MBq ¹³¹ I ⁻ , or 0.05–0.2 MBq ²¹¹ At and sacrificed 1 hour to 7 days after injection. The activities and activity concentrations in organs and tissues were determined and mean absorbed doses were calculated. The biodistribution of ¹²⁵ I ⁻ was similar to that of ¹³¹ I ⁻ but the biodistribution of free ²¹¹ At was different compared to ¹²⁵ I ⁻ and ¹³¹ I ⁻ . The activity concentration of radioiodine was higher compared with ²¹¹ At in the thyroid and lower in all extrathyroidal tissues. The mean absorbed dose per unit injected activity was highest to the thyroid. ¹³¹ I gave the highest absorbed dose to the thyroid, and ²¹¹ At gave the highest absorbed dose to all other tissues studied.

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In cancer radiotherapy, knowledge of normal tissue responses and toxicity risks is essential in order to deliver the highest possible absorbed dose to the tumor while maintaining normal tissue exposure at non-critical levels. However, few studies have investigated normal tissue responses in vivo after ²¹¹At administration. In order to identify molecular biomarkers of ionizing radiation exposure, we investigated genome-wide transcriptional responses to (very) low mean absorbed doses from ²¹¹At in normal mouse tissues. Female BALB/c nude mice were intravenously injected with 1.7 kBq ²¹¹At and killed after 1 h, 6 h, or 7 days or injected with 105 or 7.5 kBq and killed after 1 and 6 h, respectively. Controls were mock-treated. Total RNA was extracted from tissue samples of kidney cortex and medulla, liver, lungs, and spleen and subjected to microarray analysis. Enriched biological processes were categorized after cellular function based on Gene Ontology terms. Responses were tissue-specific with regard to the number of significantly regulated transcripts and associated cellular function. Dose rate effects on transcript regulation were observed with both direct and inverse trends. In several tissues, Angptl4, Per1 and Per2, and Tsc22d3 showed consistent transcript regulation at all exposure conditions. This study demonstrated tissue-specific transcriptional responses and distinct dose rate effects after ²¹¹At administration. Transcript regulation of individual genes, as well as cellular responses inferred from enriched transcript data, may serve as biomarkers in vivo. These findings expand the knowledge base on normal tissue responses and may help to evaluate and limit side effects of radionuclide therapy.