Project Identifier: LLNL-94-106
Project Title:
Introduction of a Lifetime Measurable 41CA Dose into the Bone of a Single Subject, and Direct Measurement of Vo+ and Vo-
Principle Investigator:
Dr. Stewart P. Freeman
Project started in: 1994
Project Funding Information:
Project received funding in Fiscal Year 1995.
Project used human subjects in Fiscal Year 1995.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: September 14, 1995
IRB Approval Number: 94-106
Number of Human Subjects in the Last Reporting Period for this Project: 1
(Reporting periods vary.)
Type of Human Subjects Involvement:
Objectives
We seek to develop novel methodologies for measuring human calcium (Ca) kinetics. The development at LLNL of technology capable of measuring the very long lived isotope of calcium, 41Ca (105 year halflife), at environmental levels, enables this isotope to be added to the cannon of calcium isotopic tracers. 41Ca tracer might be employed where others are precluded for radiological, physiological and/or economic reasons, thus permitting unique long-term studies of resorbing labeled bone and so-called continuous feeding studies. Here, for the first time anywhere, we demonstrate the feasibility of the continuous feeding approach with 41Ca.
Methodology
The concentration of 41Ca in feces and urine obtained during and up to 6 months after 15 days of consumption of 41Ca labeled orange juice with each meal was measured to permit the calculation of various parameters of calcium metabolism. In addition, supporting data and data for comparison were obtained by performing a conventional stable isotope test beginning on the 10th day of 41Ca consumption. On that day the test involved the administration of stable calcium isotopes IV and PO and blood draws. Excreta samples obtained that day and subsequently were also measured for the stable isotopic tracers. After appropriate preparation, the blood and excreta tracer isotope concentrations were determined by mass spectrometry. Some feces were also measured for total calcium and PEG marker concentrations.
Radioactive and Chemical Substances
Over the course of 15 days the single subject ingested a total of 34 nCi of 41Ca @ 10-6 of total calcium in the form of the carbonate dissolved in orange juice and 2.5 g/day polyethylene glycol as a fecal marker. 9.7 mg of 42Ca and 8.7 mg of 44Ca was administered IV and PO, respectively, having first been tested for sterility and pyrogenicity.
Human Subject Involvement
The subject provided urine and fecal samples and blood draws totaling 50 mL. Excreta collections were spot collections except for a one day complete urine collection and a 5-day complete fecal collection both beginning on the day of the stable isotope test.
The risks to the subject are those associated with the lifetime radiation dose from the subsequent decay of 41Ca absorbed by bone. The original pre-experiment dosimetry allowed for the ingestion of 40 nCi 41Ca of which roughly 10 nCi were to be taken up. About 40% of this was to be incorporated into the stable bone. It was anticipated that the remainder of the radiocalcium would be quickly excreted from the body and would therefore not contribute to the subsequent dose. The radiations as a consequence of decaying 41Ca have such short ranges that essentially only target organs receive a radiation dose (approx. ÂDf=0.0059 g·rad/mCi·hr). Assuming that the biological halflife of the stable bone component (and therefore the effective radionuclide halflife) is 50 years, and that the subject's survival following administration is 30 years, the anticipated cumulated radioactivity was 633 mCi·hr and the total average dose to the standard man 4 kg cortical bone was calculated to be 1 mrad or 0.03 mrem/yr. For comparison, background radiation is approximately a factor of 7000 greater. The essentially negligible dose can also be expressed in terms of cancer risk: the relative risk of a 1 mrad dose to bone is a 0.001% increase and the equivalent absolute risk is about 3 cancer cases per year per 10 billion subjects. (The subject has previously been made surgically menopausal and therefore there is no risk of a radiation dose to any fetus.) However, in practice only 34 nCi 41Ca were consumed of which an estimated 9% was absorbed into the body. Furthermore, as dietary Ca was about 1000 mg/day and bone calcium absorption was measured to be less than 10 mg/day, compared to resorption of about 100 mg/d, less 41Ca will have been incorporated into long term bone than the original pre-experiment dosimetry had supposed. Consequently, the radiation dose and attendant risks had previously been overestimated.