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Biologic Dosimetry of Bone Marrow: Induction of Micronuclei in Reticulocytes After Exposure to ³²P and ⁹⁰Y

Department of Radiology, University of Medicine and Dentistry of New Jersey–New Jersey Medical School, Newark, New Jersey

Bone marrow is the dose-limiting organ in targeted radionuclide therapy. Hence, determination of the absorbed dose to bone marrow from incorporated radionuclides is a critical element in treatment planning. This study investigated the potential of the micronucleus assay in peripheral blood reticulocytes (MnRETs) as an in vivo biologic dosimeter for bone marrow. Methods: After intravenous administration of ³²P-orthophosphate or ⁹⁰Y-citrate in Swiss Webster mice, DNA damage induced in bone marrow erythroblastoid cells was measured by subsequent scoring of MnRETs in peripheral blood. The response to exponentially decreasing dose rates was calibrated by irradiating animals with external ¹³⁷Cs–-rays. The -ray dose rate was decreased exponentially, with the dose-rate decrease half-time corresponding to the effective clearance half-time (T_e) of the radioactivity from the femoral bone (T_e = 64 h for ⁹⁰Y-citrate and T_e = 255 h for ³²P-orthophosphate). Results: The maximum MnRETs frequency occurred on the second and third day after injection of ⁹⁰Y-citrate and ³²P-orthophosphate, respectively. The same pattern was observed for exponentially decreasing dose rates of ¹³⁷Cs–-rays. For each type of exposure, the maximum MnRETs frequency increased in a dose-dependent manner. Using the calibrated dosimeter, the initial dose rates to the marrow per unit of injected activity were 0.0020 cGy/h/kBq and 0.0026 cGy/h/kBq for ³²P-orthophosphate and ⁹⁰Y-citrate, respectively. Conclusion: Micronuclei in peripheral blood reticulocytes can be used as a noninvasive biologic dosimeter for measuring absorbed dose rate and absorbed dose to bone marrow from incorporated radionuclides.

Key Words: biologic dosimetry • radionuclides • micronuclei • reticulocytes • mice • ³²P • ⁹⁰Y

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