Technetium-99m chelates of lipo-soluble EDTA analogues for biliary scintigraphy

A new class of technetium-99sup(m) chelates for biliary scintigraphy is presented. These compounds consist of technetium-99sup(m) chelated with lipo-soluble EDTA analogues. The chelating agent, ethylenediamine di(o-hydroxyphenyl acetic acid), (EDDHA), is a phenolic analogue of EDTA, its lipo-solubility and hence biliary excretion may be increased by varying the nature and degree of substitution of the phenolic ring. Technetium-99sup(m) binding to these agents by the stannous chloride reduction method is rapid and quantitative. Biliary excretion studies of one such chelates, 99sup(m)Tc-Cl-EDDHA, were performed using mice, rats and dogs. In all species the biliary excretion route predominates, in mice it accounts for 70% of the injected activity at one hour. In dogs studied with the gamma camera, activity appeared in the liver immediately after injection, and in the gall bladder 10-15 minutes later. Maximum gall bladder uptake occurred at 90 minutes post injection. In a dog with the common bile duct obstructed by ligation, the gall bladder was not visualised; instead a pattern of urinary excretion was observed with increased kidney uptake. Technetium-99sup(m)-EDDHA chelates now join 99sup(m)Tc-mercaptides and 99sup(m)Tc-pyridoxylideneglutamate as contenders for the replacement of 131I-Rose Bengal, Technetium-99sup(m)-EDDHA analogues have an advantage in that they are formulated as sterile lyophilised reagents which may be reconstituted with pertechnetate when required to give a ready-to-inject preparation. (author)