technetium-tc-99m-disofenin and iminodiacetic-acid

Tests for liver function have by and large centered around clinical laboratory diagnostic procedures for a number of years. Besides these, radiographic imaging procedures, including oral cholecystography and intravenous cholangiography, serve a very useful purpose, but several of them are invasive and involve a certain degree of risk from the administered contrast media as well as discomfort to the patient. The cholescintigraphic procedures, though noninvasive, have not played a significant role in the evaluation of hepatobiliary disorders prior to the introduction of the currently available. 99mTc-labeled IDAs. These new hepatobiliary agents offer many advantages over the previously utilized radiopharmaceuticals (131I-rose bengal in particular) in terms of the high degree of specificity for localization in the gallbladder with rapid extraction rates by the polygonal cells of the liver and very low excretion via the GU tract. A detailed understanding of the structure distribution relationship of the various groups in the complex enable the design of agents with an improvement in hepatobiliary specificity and other desirable characteristics. In many clinical situations, even in patients with high bilirubin levels, the 99m-Fc-labeled IDAs offer far superior clinical information over the alternative diagnostic imaging modalities. Further, the absorbed radiation dose imparted to the critical organs is far lower than with the older agents. Thus, the introduction of the cholescintigraphic procedures with the 99mTc-labeled IDAs have ushered in a new phase in the diagnostic workup of patients with impaired hepatocellular function and other biliary disorders.

Topics: Biliary Tract; Humans; Imino Acids; Iodine Radioisotopes; Liver; Organotechnetium Compounds; Pyridoxine; Radiation Dosage; Radioisotopes; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium; Technetium Tc 99m Disofenin; Technetium Tc 99m Lidofenin

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 (99m)Tc-BROMIDA. Log P of (99m)Tc-complexes of synthesized ligands were determined experimentally as well as the protein binding. In comparison to (99m)Tc-BROMIDA, (99m)Tc-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 (99m)Tc-DIISOPROPYLIODIDA has a prolonged hepatic transit time and decreased biliary excretion.

Topics: Aniline Compounds; Animals; Biliary Tract; Glycine; Hyperbilirubinemia; Imino Acids; Liver; Molecular Structure; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Wistar; Software; Technetium Tc 99m Diethyl-iminodiacetic Acid; Technetium Tc 99m Disofenin

In an evaluation of various 99mTc-labeled halogenated (F, Cl, Br, I) iminodiacetic acid (IDA) derivatives for hepatobiliary scintigraphy, it was found that, in the baboon model, none of these compounds performed as well as did disida. F-IDA was least effective, with the lowest biliary excretion and highest renal participation, but multihalogen substitution as in penta-F-IDA increased the biliary specificity and reduced urinary excretion to the extent that penta-F-IDA scored second to disida and even above I-IDA, with its high molecular weight. Surprising also was the relatively good performance of Cl-IDA compared to Br-IDA and I-IDA.

Topics: Animals; Biliary Tract; Halogens; Imino Acids; Liver; Organotechnetium Compounds; Papio; Radionuclide Imaging; Technetium; Technetium Tc 99m Disofenin; Tissue Distribution