PREMORTEM BIODISTRIBUTION OF RADIOACTIVITY IN THE RAT - MEASUREMENT OF BLOOD AND TISSUE ACTIVITY OF TRACERS USED IN CLINICAL IMAGING STUDIES

Radioactive tracers are used in nuclear medicine imaging studies to de tect sites of human disease. Use of animal models helps to establish t racer biodistribution kinetics and, thus, is critical to the early tes ting of radiopharmaceuticals. We developed a method to characterize th e premortem temporal, spatial, and compartmental biodistribution of tr acer molecules in the rat and used this method to study three tracers of potential value in detecting thromboembolic disease. Dynamic gamma scintigraphy was used to determine the spatial and temporal distributi on of Tc-99m-labeled IgG antifibrin antibody, Fab' fragment of antifib rin, and oxidized human serum albumin (OHSA). The blood pool compartme nt within each tissue was determined from the biodistribution of I-131 -labeled bovine serum albumin injected prior to termination. The biodi stribution of the blood compartment was maintained by immediately free zing the rat carcass in isotonic saline. Three-dimensional maps of tra cer distribution in the tissue and blood compartments were then constr ucted from cross sections of the frozen tissue. These maps were used t o relate necropsy tissue counts to premortem scintigraphic images. Ove r a 60-min interval after administration of tracer via a tail vein, si gnificant differences in biodistribution were evident. The IgG remaine d within the blood pool, but there was rapid blood clearance of the OH SA molecules by the kidney and liver. The Fab' molecules were cleared more slowly by the kidney; Fab' molecules were found in the extravascu lar spaces, whereas IgG and OHSA were not found. The kinetics of OHSA and Fab' in organ regions paralleled changes in the blood compartment. The methods described provided information that should help to define the relative value of new tracer molecules.