Evaluation of six new 99mTc-IDA agents for hepatobiliary imaging

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Abstract
IDA derivatives of three substituted benzothiazol, and two substituted chlorophenyl and one substituted pyrazoline compounds have been labeled with 99mTc and screened with four rat models with hepatocellular dysfunction manifesting varying degrees of change of liver architecture and hepatocellular damage associated with an active parenchymal destruction, fatty metamorphosis and cirrhosis. Organ distribution studies at 1 h postinjection have been compared in normal and diseased animal models for each agent labeled with 99mTc and with 99mTc-Disofenin (Disida) and Lidofenin (Hida) and 131I-Rose Bengal. From the data obtained with the six new IDA derivatives, the distribution kinetics of 99mTc-Arclophenin, (N-N′-2-benzoyl-4-chlorophenyl)carbamoylmethyl) imino diacetic acid (Phenida), are closely comparable to 99mTc-Disofenin in all animal models. Crossover patient studies (n=14) for clinical evaluation of 99mTc-Arclophenin vs 99mTc-Disofenin indicate the close similarity of the 2 agents with regard to blood pool retention, gross liver/heart ratios and liver washout, suggesting Arclofenin as a suitable agent for hepatobiliary function studies. The impaired hepatocellular animal models presented should serve for fast screening of hepatobiliary agents and enable comparison of a series of closely related compounds.

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