SYNTHESIS AND BIODISTRIBUTION OF NITRIDO TC-99M RADIOPHARMACEUTICALS WITH DITHIOPHOSPHINATE LIGANDS - A CLASS OF BRAIN IMAGING AGENTS

The symmetrical complexes [Tc-99m][TcN(R(2)PS(2))(2)] [R = CH3, CH2CH3 , CH2CH2CH3, CH2(CH3)(2)], and the unsymmetrical complex [Tc-99m][TcN( Me(2)PS(2))(Et(2)PS(2))] have been prepared, at tracer level, through a two-step procedure involving the preliminary formation of a prereduc ed technetium nitrido intermediate followed by substitution reaction o nto this species by the appropriate dithiophosphinate ligand [R(2)PS(2 )]Na. The chemical identity of the resulting complexes have been estab lished by comparison with the corresponding Tc-99-analogs prepared, at macroscopic level, by reacting the complex [(TcNCl4)-Tc-99] [n-Bu(4)N ] (n-Bu = n-butyl) with an excess of ligand in methanol, and character ized by elemental analyses and spectroscopic techniques. The complexes are neutral and lipophilic, and possess a square pyramidal geometry, with an apical Tc = N group and two dithiophosphinate ligands spanning the four positions on the basal plane through the four sulfur atoms o f the > PS2 group. In vitro studies showed that these radiopharmaceuti cals are stable in solution and that their chemical identity was not a ltered after incubation with rat blood. Biodistribution studies have b een carried out in rats and primates. The results demonstrate that the se compounds are significantly retained into the brain of these animal s for a prolonged time. Planar gamma camera images have been obtained in monkeys showing a good visualization of the cerebral region. Howeve r, the existence of persistent blood activity yields a brain/blood rat io lower than that observed with other Tc-99m-based brain perfusion im aging agents.