Structure-distribution relationship studies of 99mTc-2,3-diamine complexes.
In order to develop an organ specific radiopharmaceutical a structure-distribution relationship study was carried out in mice using a homologous series of cationic 99mTc-2,3-diaminoalkanes. The results showed that specific organ uptakes were uniformly low, generally less than 5% of the injected dose. Rapid removal of the lower homologues from the circulation through the excretory organs and an excessive blood retention of the higher homologue complexes were observed. Evidence of preferential renal clearance (over the hepatobiliary clearance) by the complexes was obtained from both linear and multiple regression analyses. Using the combined biodistribution data for the cationic diamino complexes and the equivalent anionic 99mTc-2,3-dioximinoalkane complexes, the multiple correlation was evaluated between the % urinary tract uptake data at 4 h post injection and a combination of log P, molecular diameter and charge (+1 or -1) of the complexes. From the magnitude and sign of the coefficients in the equation for the regression line, it was found that the dependence of the amount of complex cleared renally on the physico-chemical parameters tested is in the order; log P, cationic charge and molecular diameter.
Salako
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Department of Pharmaceutical Chemistry, College of Medicine, University of Lagos, Nigeria.
Theobald
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D000818:Animals; D003514:Cyclohexylamines / Q000493:pharmacokinetics*; D003959:Diamines / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D014018:Tissue Distribution
D003514:Cyclohexylamines; D003959:Diamines; C030435:1,2-cyclohexanediamine