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• W3156004908 abstract "1224 Purpose: We have recently reported the dose-dependent therapeutic effect of 211At-NaAt in differentiated thyroid cancer xenograft models. In this study, we evaluated the radiation-induced toxicity of 211At-NaAt using detailed hematological, biochemical, and histological analyses. Methods: Biodistribution of 211At-NaAt was measured in the normal ICR mice (n = 9, 38.2 ± 1.1 g), and the absorbed doses in the major organs were calculated. ICR mice groups (n = 60, 38.3 ± 1.9 g) were injected with 0.1MBq (0.10 ± 0.02 MBq, n=30) or 1 MBq (1.00 ± 0.11 MBq, n = 30) of 211At-NaAt, using saline as the control group (n = 30). Bodyweight and food intake were followed up for 60 days. The blood cell counts, serum level of total cholesterol (TC), albumin (ALB), total protein (TP), total bilirubin (T-BIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LD), blood urea nitrogen (BUN), creatine (Cr), creatine kinase (CK), amylase (AMY), and blood glucose (GLU) were measured 3, 7, 15, 29, 60 days after injection. Histological analyses of the major organs stained with hematoxylin and eosin were performed at each time point in three mice of each group. Results: The biodistribution study showed a long residence time and high absorbed dose in the thyroid gland, bladder wall, stomach wall, lungs, spleen, kidneys, and testis. The 0.1 MBq group showed no hematological, biochemical, or histological abnormalities. The 1 MBq group showed decreased body weight and weighed food intake. Hematological toxicity was mild and transient; the mean count of white blood cells, lymphocytes, and platelets enhanced on day 7 but returned to normal after day 15. The TC, ALB, and TP increased after day 3, 15, and 29, respectively, with no signs of returning to normal. Histological analysis of the 1 MBq group showed atrophy and fibrosis in the thyroid gland, a transient hypospermatogenesis in the testis on day 29 was found in one mouse, and no significant differences in the stomach or salivary gland. No hepatic or renal toxicity was observed either. Compared with previous studies that injected with 28kBq/g 211At-NaAt in mice or 44kBq/g 211At-NaAt in rats, the side effects in the present study were milder. Conclusions: High dose administration of 211At-NaAt showed transient toxicity in the white blood cells and testis without severe hematological or renal toxicity, suggesting its tolerable safety as targeted alpha-therapy for differentiated thyroid cancer.FIGURE 1. The %ID (A), %ID/g (B) and residence time (C) of the main organs in normal ICR mice administered with the 211At-NaAt solution.FIGURE 2. Change in the body weight (A) and weighed food intake (B) after administration of 211At-NaAt solution shown as mean ± SD.FIGURE 3. Evaluation of hematological toxicity in control, 0.1MBq and 1MBq group. The mean counts of WBC, lymphocytes, PLT, and RBC, are expressed as mean ± SD (*: p" @default.
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• W3156004908 date "2020-05-01" @default.
• W3156004908 modified "2023-09-23" @default.
• W3156004908 title "Preclinical evaluation of radiation-induced toxicity in targeted alpha therapy using [211At] NaAt in mice: a revisit" @default.
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