TRANSFERRIN-DEPENDENT UPTAKE AND DOSIMETRY OF AUGER-EMITTING DIAGNOSTIC RADIONUCLIDES IN HUMAN SPERMATOZOA

Localization of Auger-emitting radionuclides within spermatozoa could lead to the induction of transmissible genetic damage, We have quantif ied in vitro uptake of the widely used diagnostic Auger-emitters, In-1 11 and Tc-99m, by ejaculated human spermatozoa and investigated the ro le of transferrin in their cellular localization. The resultant dose t o sperm heads, including cellular dosimetry for Auger emissions, has b een calculated for each radionuclide and compared with that achieved u sing conventional macrodosimetry. Methods: Freshly isolated human sper matozoa were incubated in a physiological salt solution containing In- 111-chloride, Tc-99m-pertechnetate or the transferrin-binding isotope Fe-59-citrate as a positive control. Cellular uptake mechanisms were i nvestigated with transferrin competition and temperature dependence st udies. The percentage uptake of each radionuclide was determined, and the dose to individual sperm heads was calculated using both conventio nal macrodosimetric methods and by consideration of radionuclide local ization and energy deposition at the cellular level, including Auger e lectron emissions from In-111 and Tc-99m. Results: On in vitro incubat ion, human spermatozoa were found to accumulate In-111 and Fe-59 but n ot Tc-99m. Cell uptake of In-111 and Fe-59 was transferrin-mediated; h owever, an alternative transferrin-independent uptake pathway was also present for In-111. The dose to sperm heads from In-111, calculated u sing measured uptake and cellular dosimetry, was found to be larger th an that calculated using conventional dosimetry by a factor of more th an 100, In contrast, conventional dosimetry was adequate for Tc-99m an d Fe-59. Conclusion: Isolated human spermatozoa appear to accumulate t ransferrin-binding isotopes, such as the Auger-emitter In-111. If this uptake mechanism operates in the male reproductive tract, the resulta nt high dose to the sperm head could indicate that contraception may b e advisable after large diagnostic doses of In-111 and, possibly, othe r transferrin-binding radionuclides, Such precautions could prevent tr ansmission of any genetic damage from irradiated spermatozoa.