Structure-distribution relationship studies of 99mTc-2,3-dioxime complexes.
The structure-distribution relationship studies of a homologous series of anionic 99mTc-2,3-dioximinoalkanes in mice, showed very low specific organ uptakes due to a combination of rapid clearance and excessive blood binding factors as found for the cationic 99mTc-diamine analogues (Salako and Theobald, Nucl. Med. Biol. 17, 437-441; 1990. The dioxime complexes showed a preference for hepatobiliary clearance unlike the diamine complexes which were cleared through the renal tract. The relationship between the amount cleared through the biliary tract and molecular weight of the dioxime complexes is binomial, with the optimum about the C-8 chain homologue. The hepatobiliary clearance model which was discovered for these complexes follows a multiple correlation equation which has a combination of four physico-chemical properties in the order: log P, charge, protein binding and molecular weight. It was observed particularly that the log P and charge have broadly similar magnitudes (to those in the urinary model of the diamine complexes) but reversed signs. The sign on the charge coefficient is negative, indicating that an overall negative charge is required for efficient hepatobiliary extraction and excretion of these Tc-complexes.
Salako
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Q
Department of Pharmaceutical Chemistry, College of Medicine, University of Lagos, Nigeria.
Theobald
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AE
D000818:Animals; D001659:Biliary Tract / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D010091:Oximes / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D015609:Organotechnetium Compounds; D010091:Oximes