Synthesis of a novel class of nitrido Tc-99m radiopharmaceuticals with phosphino-thiol ligands showing transient heart uptake

A novel class of technetium-99m radiopharmaceuticals showing high heart uptake is described. These complexes were prepared through a simple and efficient procedure, and their molecular structure fully characterized. They are formed by a terminal Tc=N multiple bond and two bidentate phosphine-thiol ligands [R2P-(CH2)(n)SH, n = 2, 3] coordinated to the metal ion through the neutral phosphorus atom and the deprotonated thiol sulfur atom. The resulting geometry was trigonal bipyramidal. Biodistribution studies were carried out in rats. The complexes exhibited high initial heart uptake and elimination through liver and kidneys. The washout kinetic from heart was dependent on the nature of the lateral R groups on the phosphine-thiol ligands, When R = phenyl, heart activity was rapidly eliminated within 10-20 min. Instead, when R = tolyl, cyclohexyl, persistent heart uptake was observed. Extraction of activity from myocardium tissue showed that no change of the chemical identity of the tracer occurred after heart uptake. On the contrary, metabolization to more hydrophilic species occurred in liver and kidneys. NUCL MED BIOL 27;4: 369-374, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.