Testicular toxicity of the transferrin binding radionuclide super(114m)In in adult and neonatal rats

Adult (70 d) and neonatal (7 d) male rats were dosed (i.p.) with 37 MBq/kg (1 mCi/kg; approximately 1 mu g elemental indium/kg) super(114m)In, a transferrin-binding radionuclide. In adults, approximately 0.25% of the injected activity localised within the testis by 48 h postinjection and remained constant for up to 63 d. In neonates, 0.06% of the activity was in the testis by 48 h, and this declined such that by 63 d only 0.03% remained. At 63 d, treated rats had reduced sperm head counts and abnormal testicular histology that was more marked in animals dosed as adults than as neonates. In vitro, uptake of super(114m)In into seminiferous tubules isolated from 7-, 20-, or 70-d-old rats was compared with that of super(125)I. Both radionuclides were readily accumulated by the tubules. Whilst super(114m)In uptake into 20- and 70-d tubules was inhibited by excess transferrin, uptake into 7-d tubules was unchanged. super(125)I uptake was not affected by excess transferrin. These data support the contention that some radionuclides may cross the blood-testis barrier by utilisation of the physiologic iron-transferrin pathway, which may lead to greater testicular damage in adult compared to neonatal animals.