Sex and age at exposure influence 131I biodistribution and dosimetry in Sprague–Dawley rats

Abstract Background Assessing the biodistribution and absorbed dose of ¹³¹I is crucial for optimisation of radionuclide therapy, as well as for improving risk assessment following nuclear emergencies. After the Chernobyl accident, an increase in thyroid cancer among children was observed in regions affected by ¹³¹I fallout, particularly among young girls. Reasons for these age- and sex-specific differences in response to low doses of ¹³¹I are not fully understood, but variations in biodistribution and absorbed dose may be contributing factors. The aim of this study was therefore to assess the influence of sex and age at exposure on the biodistribution and dosimetry of 131 I. Methods Male and female Sprague Dawley rats were internally exposed to 0.36 MBq ¹³¹I at 5 or 17 weeks of age, corresponding to young and adult exposure groups. The 131 I activity concentration of 16 vital tissues was measured at six time points (1–144 h post-injection) and used to estimate the mean absorbed dose to each organ. Sodium-iodide symporter (NIS) protein expression was assessed using immunohistochemistry and western blot. Results The thyroid showed the highest ¹³¹I activity concentration at 18 h in males and 24 h in females, regardless of age. All non-thyroid tissues showed substantially lower activity concentrations, with the stomach having the second-highest levels. Statistically significant sex differences were determined in all tissues, with the most pronounced effect in the thyroid, where females consistently had higher activity concentrations compared to males. Age at exposure also impacted the biodistribution in some tissues. These differences led to pronounced variations in the absorbed dose. The absorbed dose to the thyroid ranged from 23 Gy/MBq in adult males to 100 Gy/MBq in young females. Protein quantification of NIS showed high individual variability but no clear difference between the groups. Conclusions The results demonstrate that sex and age at exposure affect ¹³¹I biodistribution and absorbed dose in rats, particularly in the thyroid. The observed differences in absorbed dose may partly explain the variation in susceptibility to thyroid cancer in exposed populations reported after the Chernobyl accident. Further research is needed to clarify the underlying biological and mechanistic drivers of these differences.