Synthesis and characterization of novel N 3O 3-Schiff base complexes of 99gTc, and in vivo imaging studies with analogous 99mTc complexes

Abstract

Sixteen novel derivatives of 1,1,1-tris (salicylaldiminomethyl)ethane have been synthesized for the purpose of encapsulating 99mTc(IV) ions and generating new 99mTc radiopharmaceuticals. Two methods for the preparation of the 99gTc(IV) analog complexes are presented; one utilizes SnCl 2 reduction on 99gTcO 4 − and the other a direct substitution route starting with [ 99gTcCl 6] 2−. Free ligands (H 3L) are characterized by melting points, 1H NMR, 13C NMR, mass spectroscopy, TLC, and/or elemental analyses. [ 99gTcL] + complexes are characterized by FAB-ms, UV-VIS, IR and/or CV. An X-ray structural analysis was performed on a crystal of [M(6,6′-[[2-[[((4-Methoxy-2-hydroxyphenyl)methylene)-amino]methyl]-2-methyl-1,3-propanediyl]bis(nitrilomethylidyne)]-bis-3-methoxyphenol)] tetraphenylborate, where M represents a 1 3 isomorphous mixture of 99gTc/Sn as determined by SEM. The metal coordination site is 6-coordinate, composed of N 3O 3 donor atoms, and intermediate between octahedral and trigonal prismatic geometry. The [ 99mTcL] + complexes were prepared in a stannous environment; equivalence of the 99mTc and 99gTc complexes is demonstrated by HPLC techniques. The [SnL] + complex was prepared for comparison purposes. An unusual ligand oxidation occurs for one series of ligands in which in situ amine → imine conversion is observed during the complexation reaction in reducing media. Guinea pig, rat, dog, and human metabolism studies are reported for selected [ 99mTcL] + complexes, the myocardial uptake of which approaches 2% of the injected dose.