Female and Young Rats Absorb Far More Radioactive Iodine in the Thyroid Than Adult Males

More than four decades after the Chernobyl disaster, one of its most haunting legacies remains the sharp rise in thyroid cancer among children who breathed in and ingested radioactive iodine fallout — and the puzzling fact that young girls appeared to be hit hardest. Why the burden fell so unevenly across age groups and sexes has never been fully explained. A new study from the University of Gothenburg, published in the journal Biology of Sex Differences, adds a crucial piece to the puzzle: in rats, both sex and age at exposure dramatically change where radioactive iodine-131 travels in the body and how much radiation dose the thyroid gland ultimately absorbs.

The research team, led by Anja Schroff of the Department of Medical Radiation Sciences, set out to answer a deceptively simple question with major implications for both medicine and emergency preparedness. Iodine-131 is a workhorse of nuclear medicine, used for decades to treat hyperthyroidism and certain thyroid cancers, because the thyroid gland eagerly hoards iodine to build its hormones. But the same isotope is also a signature component of nuclear accident fallout. Understanding exactly how much radiation each organ receives after exposure — and whether that dose differs between males and females, or between the young and the grown — is essential both for optimizing therapy and for refining risk estimates after a nuclear emergency.

To probe the question, the researchers gave male and female Sprague–Dawley rats a controlled internal exposure of 0.36 megabecquerels of iodine-131 at one of two life stages: five weeks of age, representing a young, still-developing animal, and seventeen weeks of age, representing adulthood. Over the following six days, they measured the activity concentration of the isotope in sixteen vital tissues at six time points, ranging from one hour to 144 hours after injection. From these time-activity data, they calculated the mean absorbed dose delivered to each organ, using both analytical methods and Monte Carlo simulations to cross-check their estimates.

The results were striking. As expected, the thyroid gland dominated the picture, showing the highest iodine-131 activity concentration of any tissue in every group — peaking at 18 hours after exposure in males and 24 hours in females, regardless of whether the animals were young or adult. Every other tissue lagged far behind, with the stomach, which also expresses iodine-transporting machinery, coming in a distant second. But the real story lay in the differences between groups, which proved to be anything but subtle.

Female rats consistently accumulated more iodine-131 in their thyroids than males, and — critically — they retained it longer. That combination of higher uptake and slower clearance translated directly into higher radiation dose. The absorbed dose to the thyroid ranged across the study groups from 23 gray per megabecquerel in adult males to a staggering 100 gray per megabecquerel in young females — a more than fourfold difference driven entirely by biological sex and age at exposure. Statistically significant sex differences emerged in all sixteen tissues examined, with the most pronounced effect in the thyroid itself.

Age mattered too, though in a sex-specific way. The most notable age-related differences in thyroid uptake and absorbed dose appeared in males: young males showed markedly higher iodine-131 uptake than adult males, resulting in a substantially greater thyroid dose. In females, whose thyroid uptake was already elevated, the age effect was less prominent. This pattern suggests that the developing thyroid — or the hormonal and metabolic milieu surrounding it — handles iodine differently depending on both its maturity and the animal’s sex, compounding rather than simply adding to the sex effect.

To understand the mechanism behind these differences, the team turned to the sodium-iodide symporter, or NIS, the membrane protein responsible for actively pumping iodide into thyroid cells. Using immunohistochemistry and western blot analysis, they quantified NIS protein expression in thyroid tissue across all groups. The result was a surprise: despite the dramatic differences in uptake and dose, NIS protein levels showed high individual variability but no clear, consistent difference between the groups. Whatever drives females and young animals to accumulate and retain more radioactive iodine, it appears not to be a simple matter of having more of the iodine transporter — hinting at deeper biological factors, perhaps involving hormone regulation, thyroid size, iodine turnover kinetics, or clearance pathways that have yet to be pinned down.

The implications reach well beyond the laboratory. After Chernobyl, epidemiological studies documented a surge in thyroid cancer among people exposed as children to iodine-131 fallout, with the increase particularly pronounced among young girls — a pattern that has long suggested some combination of biological susceptibility and dosimetric difference. This study provides the first rigorous experimental evidence that the dose itself may differ systematically by sex and age, meaning that part of the observed cancer excess could reflect the fact that young females simply received more radiation to their thyroids from the same environmental exposure. The authors are careful to note that dosimetry alone cannot explain everything — biology at the cellular level certainly contributes — but the fourfold dose range they measured is far too large to ignore in risk models.

For nuclear medicine, the findings carry a more immediate practical message. Radioiodine therapy is prescribed to patients of both sexes and all ages, yet dosing protocols have historically been built on assumptions that may not hold uniformly across the population. If sex and age influence thyroid uptake and retention as strongly in humans as they do in rats, personalized dose planning — adjusting administered activity for patient sex and age — could improve therapeutic efficacy while sparing healthy tissue. The study also underscores the value of including both sexes and multiple age groups in preclinical radiopharmaceutical research, a practice that remains inconsistent across the field.

The Gothenburg team, whose work was supported by the Swedish Radiation Safety Authority, the Swedish Research Council, and the Swedish Cancer Society, among others, emphasizes that further research is needed to clarify the underlying biological and mechanistic drivers of the observed differences. Untangling whether hormonal status, thyroid growth dynamics, renal clearance, or other factors govern the sex- and age-dependent handling of iodine will be the next step. But the core conclusion stands on its own: when it comes to radioactive iodine, who you are and how old you are when exposure happens can change the dose your thyroid receives by a factor of four — a biological reality that both radiation oncologists and emergency planners can no longer afford to overlook.

Subject of Research: How sex and age at exposure influence the biodistribution and absorbed dose of radioactive iodine-131 in rats

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

Article References: Schroff, A., Insulander Björk, K., Rassol, N., Johansson, J., Lundberg, T., Bakr, H., Andersson, M., Spetz, J., & Forssell-Aronsson, E. (2026). Sex and age at exposure influence 131I biodistribution and dosimetry in Sprague–Dawley rats. Biology of Sex Differences. https://doi.org/10.1186/s13293-026-00989-4

Image Credits: AI Generated

DOI: 10.1186/s13293-026-00989-4

Keywords: radioiodine, iodine-131, thyroid, dosimetry, biodistribution, sex differences, Chernobyl, thyroid cancer, sodium-iodide symporter, radiation protection, Sprague-Dawley rats, nuclear medicine