Evaluation of Tc-99m (V) DMSA binding to human plasma proteins

As a critical step toward elucidating the mechanism of localization of Tc-99m (V) dimercaptosuccinic acid (DMSA), we investigated its binding and transport in blood in comparison with Ga-67 citrate. The studies were performed in vitro by incubating Tc-99m (V) DMSA with blood (one sample at 4°C and another at 37°C) to assess its binding to plasma proteins using ultrafiltration, dialysis, electrophoresis, gel filtration chromatography and affinity chromatography. A parallel experiment for determining the blood binding of Ga-67 citrate was performed using the same procedures. Using ultrafiltration, dialysis, electrophoresis and gel filtration chromatography, labeled plasma samples showed that protein binding for Tc-99m (V) DMSA was 45-54% at 37°C and 73-80% at 4°C. The figures for Ga-67 citrate were 43-53% at 37°C and 75-81% at 4°C. Electrophoresis showed that Tc-99m (V) DMSA was mostly bound to plasma albumin (36.05 ± 2.48% at 37°C and 60.04 ± 1.87% at 4°C), and that the proportion of Ga-67 radioactivity associated with β-globulin was 34.23 ± 1.37% at 37°C and 55.71 ± 3.69% at 4°C. In affinity chromatography experiments, Tc-99m (V) DMSA did not bind to transferrin, unlike Ga-67 citrate. This study demonstrates that, at the radiopharmaceutical tracer level, most Tc-99m (V) DMSA in blood is protein-bound, primarily to albumin, but not to transferrin. In contrast, Ga-67 citrate was bound primarily to transferrin. The knowledge that albumin is the main transport protein of Tc-99m (V) DMSA may contribute to a better understanding of its biodistribution and pharmacokinetics.