Synthesis and characterization of novel N3O3-Schiff base complexes of 99gTc, and in vivo imaging studies with analogous 99mTc complexes.
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 SnCl2 reduction on 99gTcO4- and the other a direct substitution route starting with [99gTcCl6]2-. Free ligands (H3L) 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 N3O3 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.
Mallinckrodt Medical, Inc., St. Louis, MO 63134, USA.
M E
ME
Marmion
S R
SR
Woulfe
W L
WL
Newmann
G
G
Pilcher
D L
DL
Nosco
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006168:Guinea Pigs; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D007202:Indicators and Reagents; D008024:Ligands; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011877:Radionuclide Imaging; D051381:Rats; D012545:Schiff Bases; D013667:Technetium; D017556:Technetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D007202:Indicators and Reagents; D008024:Ligands; D012545:Schiff Bases; D017556:Technetium Compounds; D013667:Technetium