Background: The long-lived radioisotope, 41Ca, is an ideal candidate for biological tracer studies because the background signal of 41Ca is essentially zero. The advantage of combining a marker such as 41Ca (low noise with a technique such as accelerator mass spectrometry, is that excellent signal/noise can be obtained from ng quantities of isotopes administered. We describe the development of an intravenous 41Ca dose suitable for humans, analytical method validation for measuring 41Ca/Ca isotope ratios in biological samples, and experiments with eight human volunteers dosed with 10 nCi of 41Ca. Methods: Using sterile techniques 41Ca was formulated and aliquotted into individual vials and to the extent possible, the 41Ca doses were tested according to USP guidelines. Measurement of 41Ca/Ca ratios in serum were made by accelerator mass spectrometry after isolating calcium with three precipitation steps and a cation exchange column. Four healthy controls and four end stage renal disease patients on hemodialysis were dosed with 10 nCi of 41Ca and distribution kinetics were determined over 168 days. Results: The dosing solution was chemically and radiologically pure, contained < 0.1 endotoxin unit per mL (Eu/mL) and passed USP sterility tests. The analytical method for quantification of the 41Ca/Ca ratios was linear from 6 x 10-14 to 9.1 x 10-10. The run to run precision of the method was 3 % and 2 % at 9.1 x 10-11 and 9.1 x 10-10 respectively. The area under the curve (AUC), representing the time course of 41Ca in the central compartment, was significantly less for end stage renal disease patients patients as compared with control subjects (p < 0.005). Conclusions: The calculated overall radiation dose commitment of 0.06 µSv for the first year following a 10 nCi dose of 41Ca is a factor 30,000 times smaller than the total dose from natural radiation. The biological risks associated with this low level radiation exposure are to small to quantify. The 41Ca dose was administered to eight volunteers without adverse effects. Accelerator mass spectrometry was used to measure isotope ratios that span 5 orders of magnitude with excellent precision in the range observed after administration of 10 nCi 41Ca. For the first time, we show that 41Ca can be used to monitor differences in bone turnover between normal subjects and ESRD patients.
See more of AMS in Low Dose Bioscience Workshop
See more of The 10th International Conference on Accelerator Mass Spectrometry (September 5-10, 2005)