Correlation between lipophilicity of the ligands and the hepatobiliary properties of the radiopharmaceuticals: Approach to the development of new IDA derivatives

The partition coefficient (log P) for n-octanol/water system was calculated applying PACO program for various theoretically possible mono and dihalogenated IDA derivatives. Some of the synthesized ligands (SOLCOIODIDA, IODIDA and DIIODIDA) were labeled with the technetium-99m. The biodistribution and influence of bilirubin on their biokinetics were investigated in rats. The correlation between partition coefficients of ligands increase (log P) and better hepatobiliary properties of Tc-99m-IDA derivatives was determined. The values of log P increase from 1.16 for SOLCOIODIDA, 3.11 for IODIDA to 3.47 for DIIODIDA. In correlation with these results, biliary excretion decreased for 59% for Tc-99m-SOLCOIODIDA and 11% for Tc-99m-IODIDA and Tc-99m-DIIODIDA under hyperbilirubinemia (3.5 min after injection) and 45%, 11% and 0.38% respectively (15 min after injection). The highest biliary excretion had Tc-99m-DIIODIDA (55.4% for 3.5 min). Considering the correlation between hepatobiliary properties and log P, the evaluation of biological properties for various trifluoromethyl mono and dihalogenated IDA derivatives was performed on the basis of the calculated log P in order to synthetize a new radiopharmaceutical for hepatobiliary scintigraphy

New Tc-99m-diiodine substituted IDA derivative (DIIODIDA) for hepatobiliary imaging

A new diiodine substituted LDA derivative, 2,4-diiodine-6-methyl IDA (DIIODIDA) was synthesized and labeled with Tc-99m. It was established that Tc-99m-DIIODIDA had high radiochemical purity. Biodistribution and influence of bilirubin on Tc-99m-DIIODIDA biokinetics has been studied in rats and compared to the corresponding results for Tc-99m-SOLCOIODIDA. Related to Tc-99m-SOLCOIODIDA, Tc-99m-DIIODIDA has much better biliary exretion (55.18 versus 43.63%). No change of Tc-99m-DIIODIDA biokinetics, under influence of bilirubin was noticed. Biliary excretion of Tc-99m-SOLCOIODIDA has been reduced for about 60%. The protein binding of Tc-99m-DIIODIDA and Tc-99m-SOLCOIODIDA were also determined, using in vitro method of precipitation. These results showed that Tc-99m-DIIODIDA hepatobiliary imaging agent is superior to the presently used Tc-99m-monoiodine IDA derivatives