Disposition of [ 14C]dimercaptosuccinic acid in mice

Abstract

Dimercaptosuccinic acid labeled with 14C ([ 14C]DMSA) was administered to mice iv; the mice were frozen by immersion in dry ice/hexane at 6 and 20 min and 1, 3, 9, and 24 hr after injection. The frozen mice were sectioned and processed for whole-body autoradiography for soluble substances. The radioactivity was highly localized in extracellular fluids such as the subcutaneous, intrapleural, intraperitoneal, and periosteal spaces. There was a pronounced accumulation in the periosteal fluid above that in other fluids during the first hour after injection. Most of the radioactivity was eliminated by the kidney and liver. Pretreatment of a mouse with HgCl 2 subcutaneously 1 hr before [ 14C]DMSA produced an increase in radioactivity in the liver and decrease in lung. A high concentration of radioactivity was seen at the subcutaneous site of injection of the HgCl 2. The results are interpreted to indicate that most of the DMSA is in the extracellular space but that it can cross cellular membranes to some extent. The pronounced accumulation in periosteal fluid may be an interaction of DMSA with Ca 2+ in this space. No tissue had a pronounced retention of the compound, but lung retained more than most other tissues.