IN-VITRO AND IN-VIVO STUDIES WITH PENTAVALENT TC-99M DIMERCAPTOSUCCINIC ACID

The purpose of this investigation was to characterise the in vivo chem istry and binding mechanisms of technetium-99m dimercaptosuccinic acid [Tc-99m(V)DMSA]. Biodistribution was studied in mice by frozen sectio n whole-body autoradiography and microautoradiography in selected tiss ues. Binding to bone mineral analogues was studied in vitro using vari ous forms of calcium phosphate and hydroxyapatite under varied conditi ons, Similar studies with Tc-99m-hydroxymethylene diphosphonate (HDP) were also carried out for comparison. The in vivo stability of Tc-99m( V)DMSA was monitored by high-performance liquid chromate graphic analy sis of blood and urine samples taken over 24 h from patients injected with the tracer, Whole-body autoradiography shows that Tc-99m(V)DMSA h as highest affinity for bone (cortical rather than medullary) in mice. Substantial uptake of the tracer was also observed in the kidney (cyt oplasm of cortical renal tubular cells). No specific localisation was observed in the liver at either the microscopic or the macroscopic lev el. While Tc-99m-HDP bound strongly to calcium phosphates under all co nditions, Tc-99m(V)DMSA binding was inhibited in the presence of phosp hate and was stronger at pH 6.0 than at pH 7.4. In non-phosphate buffe rs, however, the binding of Tc-99m(V)DMSA remained high across the pH range 4-7.4. Tc-99m(V)DMSA binds to calcium phosphates chemically unal tered, and no radioactive species other than the three isomers of Tc-9 9m(V)DMSA were detected in blood or urine samples taken from patients up to 24 h after injection. Tc-99m(V)DMSA is stable in vivo, and no co nversion of the complex to other chemical species needs to be invoked to explain its uptake in bone metastases or soft tissue tumour. Bone a ffinity may be due to reversible binding of the unaltered complex to t he mineral phase of bone.