title: Microdistribution and localized dosimetry of the alpha-emitting radionuclides 239Pu, 241Am and 233U in mouse femoral shaft.
abstract: OBJECTIVE
  To analyse the temporal change in microdistribution of 239Pu, 241Am and 233U in mouse femur and to compare the calculated radiation doses with regions of the bone marrow thought to contain target cells for osteosarcoma and leukaemia with relative risk for those diseases.
  
  
  METHODS
  Neutron-induced and alpha-track autoradiographs were prepared from femora of the CBA/H mouse that had been injected with 40 kBq kg(-1) radionuclide between 1 and 448 days previously. Computer-based image analysis of the autoradiographs was performed and dosimetric methods applied to obtain radiation dose-rates to different regions of the marrow cavity.
  
  
  RESULTS
  Initially each radionuclide deposited on endosteal and periosteal bone surfaces; 241Am was additionally deposited on vascular canal surfaces. Redistribution resulted in 233U being incorporated into bone, while 239Pu and 241Am showed transfer into both bone volume and marrow. Accumulation in the central marrow peaked at 112-224 days post-injection, but subsequently was cleared by 448 days. Cumulative doses to both osteosarcomagenic and myeloid leukaemogenic target cell regions showed the trend 239Pu > 241Am > 233U.
  
  
  CONCLUSIONS
  Calculation of cumulative doses to a 10-microm layer of marrow adjacent to bone surfaces appears to be a suitable predictor for risk of osteosarcoma. Risks of myeloid leukaemia in the mouse are better predicted by considering the central marrow as the target region rather than average dose to all marrow.
authors.affiliation: CRC Section of Haemopoietic Cell and Gene Therapeutics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK. acartlidge@picr.man.ac.uk
authors.forename: A L
authors.initials: AL
authors.lastname: Austin
authors.forename: M
authors.initials: M
authors.lastname: Ellender
authors.forename: J W
authors.initials: JW
authors.lastname: Haines
authors.forename: J D
authors.initials: JD
authors.lastname: Harrison
authors.forename: B I
authors.initials: BI
authors.lastname: Lord
mesh_terms: D000512:Alpha Particles; D000576:Americium / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography; D001853:Bone Marrow / Q000378:metabolism; D005260:Female; D005269:Femur / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009502:Neutrons; D011005:Plutonium / Q000493:pharmacokinetics*; D011874:Radiometry; D012307:Risk Factors; D013997:Time Factors; D014501:Uranium / Q000493:pharmacokinetics*
chemical_list: D014501:Uranium; D011005:Plutonium; D000576:Americium