The effect of lipophilicity on the hepatobiliary properties of iminodiacetic acid derivatives in the conditions of hyperbilirubinemia

• Published in: Applied radiation and isotopes 2013-04, Vol.74, p.31-35
• Main Authors: Brborić, J., Jovanović, M.S., Vranješ-Đurić, S., Čudina, O., Marković, B., Vladimirov, S.
• Format: Article
• Language: English
• Subjects: Animals; Biliary Tract - diagnostic imaging; BROMIDA; DIETHYLIODIDA; DIISOPROPYLIODIDA; Hepatobiliary scintigraphy; Hyperbilirubinemia - diagnostic imaging; Imino Acids - chemistry; Lipophilicity; Liver - diagnostic imaging; Molecular Structure; Organotechnetium Compounds - chemistry; Radionuclide Imaging; Radiopharmaceuticals - chemistry; Rats; Rats, Wistar; Software; Technetium Tc 99m Diethyl-iminodiacetic Acid - chemistry; Technetium Tc 99m Disofenin - chemistry
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/j.apradiso.2012.12.014

The partition coefficients (log P) of theoretically possible alkyliodinated iminodiacetic acid (IDA) derivatives and commercial IDA derivatives were calculated using two computer programs: ChemSketch Log P and ChemOffice Ultra. Newly synthesized ligands (DIETHYLIODIDA and DIISOPROPYLIODIDA) with the highest calculated log P were labeled with technetium-99m. The biodistribution and the influence of bilirubin on their biokinetics were investigated in rats and compared to corresponding results for commercial 99mTc-BROMIDA. Log P of 99mTc-complexes of synthesized ligands were determined experimentally as well as the protein binding. In comparison to 99mTc-BROMIDA, 99mTc-DIETHYLIODIDA has: (a) better biliary excretion (2.76±0.15%ID/g versus 1.83±0.10%ID/g); (b) faster hepatic clearance (2.90±0.21%ID/g versus 7.47±0.70%ID/g) and decreased biliary excretion (for 14% versus 22%) in conditions of hyperbilirubinemia after 15min. It is proved that 99mTc-DIISOPROPYLIODIDA has a prolonged hepatic transit time and decreased biliary excretion. ► In this study we investigated the effect of lipophilicity on the hepatobiliary properties of IDA derivatives. ► Log P of alkyliodinated IDA derivatives and commercial IDA derivatives were calculated. ► Newly synthesized ligands with the highest calculated log P were labeled with 99mTc. ► Log P of those complexes were determined experimentally. ► The biodistribution and the influence of bilirubin on their biokinetics were investigated in rats.