Biologic dosimetry of bone marrow: Induction of micronuclei in reticulocytes after exposure to P-32 and Y-90

Bone marrow is the dose-limiting organ in targeted radionuclide therapy. He nce, determination of the absorbed dose to bone marrow from incorporated ra dionuclides is a critical: element in treatment planning. This study invest igated the potential of the micronucleus assay in peripheral blood reticulo cytes (MnRETs) as an in vivo biologic dosimeter for bone marrow. Methods: A fter intravenous administration of P-32-orthophosphate or Y-90-citrate in S wiss Webster mice, DNA damage induced in bone marrow erythroblastoid cells was measured by subsequent scoring of MnRETs in peripheral blood. The respo nse to exponentially decreasing dose rates was calibrated by irradiating an imals with external Cs-137-gamma -rays. The gamma -ray dose rate was decrea sed exponentially, with the dose-rate decrease half-time corresponding to t he effective clearance half-time (T-e) of the radioactivity from the femora l bone (T-e = 64 h for Y-90-citrate and T-e = 255 h for P-32-orthophosphate ). Results: The maximum MnRETs frequency occurred on the second and third d ay after injection of Y-90-citrate and P-32-orthophosphate, respectively. T he same pattern was observed for exponentially decreasing dose rates of Cs- 137-gamma -rays. For each type of exposure, the maximum MnREts frequency in creased in a dose-dependent manner. Using the calibrated dosimeter, the ini tial dose rates to the marrow per unit of injected activity were 0.0020 cGy /h/kBq and 0.0026 cGy/h/kBq for P-32-orthophosphate and Y-90-citrate, respe ctively. Conclusion: Micronuclei in peripheral blood reticulocytes can be u sed as a noninvasive biologic dosimeter for measuring absorbed dose rate an d absorbed dose to bone marrow from incorporated radionuclides.