Premortem biodistribution of radioactivity in the rat: measurement of blood and tissue activity of tracers used in clinical imaging studies
Line, B.R.; Herrmannsdoerfer, A.J.; Battles, A.H.; Weber, P.B.; Dansereau, R.N.; Blumenstock, F.A.
Laboratory Animal Science 44(5): 495-502
1994
ISSN/ISBN: 0023-6764 PMID: 7844960 Document Number: 435671
Radioactive tracers are used in nuclear medicine imaging studies to detect sites of human disease. Use of animal models helps to establish tracer biodistribution kinetics and, thus, is critical to the early testing of radiopharmaceuticals. We developed a method to characterize the premortem temporal, spatial, and compartmental biodistribution of tracer 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 distribution of 99mTc-labeled IgG antifibrin antibody, Fab' fragment of antifibrin, and oxidized human serum albumin (OHSA). The blood pool compartment within each tissue was determined from the biodistribution of 131I-labeled bovine serum albumin injected prior to termination. The biodistribution of the blood compartment was maintained by immediately freezing the rat carcass in isotonic saline. Three-dimensional maps of tracer distribution in the tissue and blood compartments were then constructed from cross sections of the frozen tissue. These maps were used to relate necropsy tissue counts to premortem scintigraphic images. Over a 60-min interval after administration of tracer via a tail vein, significant differences in biodistribution were evident. The IgG remained within the blood pool, but there was rapid blood clearance of the OHSA molecules by the kidney and liver. The Fab' molecules were cleared more slowly by the kidney; Fab' molecules were found in the extravascular 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.