The validity of using stable isotopes of the low-toxicity elements Eu, Gd and Hf as surrogates for the highly radiotoxic actinides Am, Cm and Pu, respectively, for studies of their biokinetics in human subjects of all ages was established. The technique of computer simulation of chemical speciation was used to investigate the chemical interactions of Hf, Eu and Gd with the biologically important ligands acetate, lactate, tartrate, citrate and oxalate, and to compare them with those of Pu, Am and Cm. The speciation data, together with published information on the biochemical and physiological behaviour of these elements in animals were compared in order to assess the validity of using Hf, Eu, and Gd as surrogates for Pu, Am and Cm, respectively.
The speciation studies suggest that Eu can be used as an analogue for Am, although Gd could be a better choice. However, the differences between Gd(3+) and Cm(3+) indicate that the former is not a very suitable analogue for Cm.
The original assumption that Hf could act as a surrogate for Pu was based on the similarity of their ionic charge and radius. Consideration of all the information now available indicates that Hf could, with caution, be used as a surrogate for Pu for studies of the absorption from the gastrointestinal tract. However, the observed differences in the tissue distributions of the two elements in animals, and in their in vitro speciation profiles, show that Hf does not mimic the behaviour of Pu in vivo sufficiently accurately for it to be regarded as a reliable general surrogate for Pu in human studies.
The hypothesis that certain lanthanide elements could be used as surrogates for corresponding members of the actinide series is based on the well-known general chemical similarities between the two families of elements. The results obtained show that while there are some, relatively small differences in the magnitude of the uptake of the two actinides and the two lanthanides in liver and skeleton, the retention pattern is generally similar. This reinforces the conclusions drawn from the speciation studies that Eu and Gd could be used as reasonable surrogates for Am and Cm for biokinetic studies in humans. However, the speciation studies do indicate that there are some variations between Gd and Cm which, although these do not appear to influence their general pattern of biological distribution and clearance in vivo, might possibly be reflected in non-trivial differences in the detailed molecular interactions of Gd and Am with the components of cells and tissues. It appears most likely that the four elements do exhibit essentially similar behaviour in the gastrointestinal tract and in their transfer from there to blood. Thus Eu and Gd can be considered, to a first approximation, to mimic the behaviour of Am and Cm sufficiently well for stable isotopes of these elements to be used as surrogates in human studies.
The global objective of this project is to evaluate the use of stable isotopes as tracers in metabolic investigations in humans to meet the accepted and continuing need for more realistic biokinetic data of toxic radioelements of relevance in radiation protection. The transfer of radionuclides into the human body via the food chain will be investigated by experimental studies in man, with particular attention to the reliability and variability of transfer parameters under realistic conditions. Additional investigations on the internal distribution and excretion patterns will improve the metabolic and dosimetric models and consequently the dose assessments of internal exposure.
The metabolic behaviour of some radionuclides will be studied by sustituting the radioactive isotopes by stable isotopes of the same element as tracers. Uptake of molybdenum, zirconium and cerium into the human body via the food chain will be studied using stable isotopes of the respective elements. The possibility of developing counter measures designed to reduce the intestinal absorption of molybdenum in emergency situations will be evaluated.For plutonium and other actinides, where no stable isotopes exist, stable analogues will be used in metabolic studies. The use of selected elements of the lanthanide series as surrogates for actinides in stable element tracer studies in human volunteers could provide valuable information which is not otherwise obtainable by planned systematic investigations. The metabolic behaviour of plutonium in the human body will be investigated using stable hafnium as surrogate. The use of europium and gadolinium as analogues for americium and curium for studies in humans will be validated. The metabolism of barium and neodymium in man will be investigated by ingestion and intravenous injection of stable isotopes, as surrogates for radium and the actinides as well as to provide additional information on the behaviour of barium in humans. The data obtained will be used to prove and modify the metabolic and dosimetric models for these elements and to revise the dose calculations for the incorporation of the respective radionuclides.
The goals of this project require the close collaboration of several laboratories to contribute with their special expertise and experience in the different aspects involved in this tasks.
Funding SchemeCSC - Cost-sharing contracts
OX11 0RA Didcot
CF1 3TB Cardiff