SYNTHESIS AND CHARACTERIZATION OF NEUTRAL TECHNETIUM(III)-99 AND TECHNETIUM(III)-99M COMPLEXES WITH O,P-BIDENTATE PHOSPHINO-CARBOXYLATE LIGANDS - CRYSTAL-STRUCTURE OF MER-[TC(O2CCH2CH2PPH2)3]CENTER-DOT-2ME2SO

Reduction-substitution reactions of pertechnetate with a class of O,P-bidentate phosphinocarboxylic acid ligands HL(n) [n = 1, 2-(diphenylphosphino)benzoic acid; n = 2, 3-(diphenylphosphino)propionic acid; n = 3, (diphenylphosphino)acetic acid; n = 4, 3-(diethylphosphino)propionic acid] afforded a series of neutral and paramagnetic [TcL3n] complexes. The products have been characterized by means of elemental analysis, IR, H-1 NMR, UV/VIS and FAB mass spectroscopy, and X-ray crystallography for (TcL2(3)]. The latter crystallizes in the monoclinic space group P2(1)/n with Z = 4, a = 21.718(10). b = 12.954(6), c = 18.038(9) angstrom and beta = 106.59(4)-degrees. The final R value was 0.061. Three deprotonated chelates surround the metal in a distorted-octahedral environment adopting a meridional configuration, and consequently there are two pairs of like donor atoms trans to one another with the remaining phosphorus atom trans to an oxygen atom. Similar reduction-substitution reactions have been performed utilizing the short-lived isotope Tc-99m. The physicochemical properties of the resulting Tc-99m-labelled species match very well those exhibited by the analogues prepared with the long-lived isotope Tc-99m. Thus the chemical structures of [Tc(99m)L3n] and [Tc-99L3n] analogues are identical. Female Sprague-Dawley rats were injected with pre-purified [Tc(99m)L3n] (n = 1, 2 or 4) and the resulting biodistributions evaluated at different times post injection. All the complexes undergo very low, but significant, brain uptake which decreases with time.