SYNTHESIS AND CHARACTERIZATION OF NOVEL N3O3-SCHIFF BASE COMPLEXES OFTC-99G, AND IN-VIVO IMAGING STUDIES WITH ANALOGOUS TC-99M COMPLEXES

Sixteen novel derivatives of 1,1,1-tris (salicylaldiminomethyl)ethane have been synthesized for the purpose of encapsulating Tc-99m(IV) ions and generating new Tc-99m radiopharmaceuticals. Two methods for the p reparation of the Tc-99g(IV) analog complexes are presented; one utili zes SnCl2 reduction on (TcO4-)-Tc-99g and the other a direct substitut ion route starting with [(TcCl6)-Tc-99g](2-). Free ligands (H(3)L) are characterized by melting points, H-1 NMR, C-13 NMR, mass spectroscopy , TLC, and/or elemental analyses. [(99g)TcL](+) complexes are characte rized by FAB-ms, UV-VIS, IR and/or CV. An X-ray structural analysis wa s performed on a crystal of iyl]bis(nitrilomethylidyne)]-bis-3-methoxy phenol)] tetraphenylborate, where M represents a 1/3 isomorphous mixtu re of Tc-99g/Sn as determined by SEM. The metal coordination site is 6 -coordinate, composed of N3O3 donor atoms, and intermediate between oc tahedral and trigonal prismatic geometry. The [(99m)TcL](+) complexes were prepared in a stannous environment; equivalence of the Tc-99m and Tc-99g complexes is demonstrated by HPLC techniques. The [SnL](+) com plex was prepared for comparison purposes. An unusual ligand oxidation occurs for one series of ligands in which in situ amine --> imine con version is observed during the complexation reaction in reducing media . Guinea pig, rat, dog, and human metabolism studies are reported for selected [(99m)TcL](+) complexes, the myocardial uptake of which appro aches 2% of the injected dose.