Project Identifier: LLNL-95-109
Project Title:
An Investigation of Human Calcium Kinetics Using 41Ca and Stable Isotope Labeled Calcium
Principle Investigator:
Dr. Stewart P. Freeman
Project started in: 1995
Project Funding Information:
Project did not receive funding in Fiscal Year 1995.
Project did not use human subjects in Fiscal Year 1995.
Explanation:
Human use to begin in FY 1996. Experiment to begin in FY 1996 and to be funded by Laboratory Directed Research Development.
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: March 22, 1995
IRB Approval Number: 95-109
Number of Human Subjects in the Last Reporting Period for this Project: 0
(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 canon 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, having previously demonstrated the feasibility of the continuous feeding approach, we attempt to do so again with a second subject in order to obtain further data.
Methodology
The concentration of 41Ca in feces and urine obtained before, during and up to 6 months after 15 days of consumption of 41Ca-labeled orange juice with each meal will be measured to permit the calculation of various parameters of calcium metabolism. In addition, supporting data and data for comparison will be obtained by performing a conventional stable isotope test beginning on the 10th day of 41Ca consumption. That day the test will involve the administration of stable calcium isotopes IV and PO and blood draws. Excreta samples obtained that day and subsequently will also be measured for the stable isotopic tracers. After appropriate preparation, the blood and excreta tracer isotope concentrations will be determined by mass spectrometry.
Radioactive and Chemical Substances
The single subject will ingest a total of 40 nCi 41Ca @ 10-6 of total calcium in the form of the carbonate dissolved in orange juice. 2 µg/kg 46Ca and 0.5 mg/kg 44Ca will be administered IV and PO, respectively, having first been tested for sterility and pyrogenicity.
Human Subject Involvement
The subject will provide urine, fecal and nine 3-mL blood samples. Excreta collections will be spot collections except for a 3-day complete urine collection and week-long complete fecal collection 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. 40 nCi 41Ca will be ingested of which roughly 10 nCi will be taken up. About 40% of this will be incorporated into the stable bone. The remainder of the radiocalcium will be quickly excreted from the body and is assumed not to contribute to the dose. The radiations as a consequence of decaying 41Ca have such short ranges that essentially only the 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 survival post administration is 30 years, the cumulated radioactivity will be 633 (mCi) (hr) and the total average dose to the standard man 4 kg cortical bone mass will be 1 mrad or 0.03 mrem/year. 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.)