Extrapolation from animals to the human for the retention of radiothallium in the blood

The extrapolation of tissue distribution data from animal to human has implications in the clinical application of new radiopharmaceuticals, in studies of biodistribution and biokinetics, and in estimation of radiation absorbed dose. The extrapolative method described in this study is based on the assumption that the mechanism of tissue distribution of a radionuclide in different mammalian species is similar. This assumption implies that the fractional distribution function, α/sub h/(t), of a radionuclide in a specific tissue of one species is related to the corresponding fractional distribution function in any other species by linear transformations in the activity and time variables. Hence, the successful application of the extrapolative technique requires determining a reference α/sub h/(t) based on a conveniently studied species and finding the relationships between the factors of the transformations and one or more measurable species-dependent parameters. To test this approach, data for retention of T1-201 in the blood of several species were used. Detailed biokinetic data in mice, collected in our laboratory, were used to determine the reference α/sub h/(t) mouse. Data for other species were extracted from the literature and compared with α/sub h/(t) mouse to determine the transformation factors, using the least squares fitting technique. These factors appear, on the basis of the data available, to be power functions of body weight. Retention of activity in blood was chosen as a test of the theory because data have been published for several nonhuman species as well as verifying values for the human