Chronic cognitive deficits and amyloid precursor protein elevation after selective immunotoxin lesions of the basal forebrain cholinergic system

The biological response of bone marrow to incorporated radionuclides depends on several factors such as absorbed dose, dose rate, proliferation and marrow reserve. The determination of the dose rate and absorbed dose to bone marrow from incorporated radionuclides is complex. This research used survival of granulocyte-macrophage colony-forming cells (GM-CFCs) as a biological dosimeter to determine experimentally the dose rate and dose to bone marrow after administration of 90Y-citrate. METHODS: The radiochemical 90Y-citrate was administered intravenously to Swiss Webster mice. Biokinetics studies indicated that the injected 90Y quickly localized in the femurs (0.8% ID/femur) and cleared with an effective half-time of 62 hr. Subsequently, GM-CFC survival was determined as a function of femur uptake and injected activity. Finally, to calibrate GM-CFC survival as a biological dosimeter, mice were irradiated with external 137Cs gamma rays at dose rates that decreased exponentially with a half-time of 62 hr. RESULTS: Femur uptake was linearly proportional to injected activity. The survival of GM-CFCs was exponentially dependent on both the initial 90Y femur activity and the initial dose rate from external 137Cs gamma rays with 5.1 kBq/femur and 1.9 cGy/hr, respectively, required to achieve 37% survival. Thus, 90Y-citrate delivers a dose rate of 0.37 cGy/hr to the femoral marrow per kBq of femur activity and the dose rate decreased with an effective half-time of 62 hr. CONCLUSION: Survival of GM-CFCs can serve as a biological dosimeter to experimentally determine the dose rate kinetics in bone marrow.