title: Transferrin-dependent uptake and dosimetry of Auger-emitting diagnostic radionuclides in human spermatozoa.
abstract: Localization of Auger-emitting radionuclides within spermatozoa could lead to the induction of transmissible genetic damage. We have quantified in vitro uptake of the widely used diagnostic Auger-emitters, (111)In and 99mTc, by ejaculated human spermatozoa and investigated the role of transferrin in their cellular localization. The resultant dose to sperm heads, including cellular dosimetry for Auger emissions, has been calculated for each radionuclide and compared with that achieved using conventional macrodosimetry.
  
  
  METHODS
  Freshly isolated human spermatozoa were incubated in a physiological salt solution containing (111)In-chloride, 99mTc-pertechnetate or the transferrin-binding isotope 59Fe-citrate as a positive control. Cellular uptake mechanisms were investigated with transferrin competition and temperature dependence studies. The percentage uptake of each radionuclide was determined, and the dose to individual sperm heads was calculated using both conventional macrodosimetric methods and by consideration of radionuclide localization and energy deposition at the cellular level, including Auger electron emissions from (111)In and 99mTc.
  
  
  RESULTS
  On in vitro incubation, human spermatozoa were found to accumulate (111)In and 59Fe but not 99mTc. Cell uptake of (111)In and 59Fe was transferrin-mediated; however, an alternative transferrin-independent uptake pathway was also present for (111)In. The dose to sperm heads from (111)In, calculated using measured uptake and cellular dosimetry, was found to be larger than that calculated using conventional dosimetry by a factor of more than 100. In contrast, conventional dosimetry was adequate for 99mTc and 59Fe.
  
  
  CONCLUSIONS
  Isolated human spermatozoa appear to accumulate transferrin-binding isotopes, such as the Auger-emitter (111)In. If this uptake mechanism operates in the male reproductive tract, the resultant high dose to the sperm head could indicate that contraception may be advisable after large diagnostic doses of (111)In and, possibly, other transferrin-binding radionuclides. Such precautions could prevent transmission of any genetic damage from irradiated spermatozoa.
authors.affiliation: School of Biological Sciences, University of Manchester, and Manchester Royal Infirmary, United Kingdom.
authors.forename: K P
authors.initials: KP
authors.lastname: Hoyes
authors.forename: J S
authors.initials: JS
authors.lastname: Nettleton
authors.forename: R S
authors.initials: RS
authors.lastname: Lawson
authors.forename: I D
authors.initials: ID
authors.lastname: Morris
mesh_terms: D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D007504:Iron Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D011829:Radiation Dosage; D011835:Radiation Protection; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013670:Sodium Pertechnetate Tc 99m / Q000493:pharmacokinetics*; D013077:Sperm Head / Q000528:radiation effects; D013094:Spermatozoa / Q000378:metabolism* / Q000528:radiation effects; D014168:Transferrin / Q000378:metabolism*
chemical_list: D007205:Indium Radioisotopes; D007504:Iron Radioisotopes; D019275:Radiopharmaceuticals; D014168:Transferrin; D013670:Sodium Pertechnetate Tc 99m