Pharmacokinetic models to evaluate radiolabeling reagents for protein radiopharmaceuticals

Nucl Med Biol. 1998 Jan;25(1):31-6. doi: 10.1016/s0969-8051(97)00152-2.

Abstract

Pharmacokinetic models were constructed to further estimate the hepatic radioactivity levels derived from bifunctional chelating agents used for radiolabeling of proteins. Both galactosyl-neoglycoalbumin (NGA) and mannosyl-neoglycoalbumin (NMA) were labeled with (111)In using two benzyl-EDTA derivatives. Time-activity profiles for the liver with gallbladder, intestine, and blood after administration of (111)In-labeled NGAs in mice were simultaneously fitted to a multi-compartment model, and the first-order rate constants representing the disappearance from parenchymal cells were obtained. Similarly, a model composed of the blood and liver compartment was constructed, and the disappearance rate constants from nonparenchymal cells were calculated from the biodistribution studies following administrations of (111)In-labeled NMAs. Fitting curves showed good agreements with the experimental data. Each rate constant clearly distinguished the elimination rate of the respective radiometabolite from the liver cells. Thus, quantitative estimations of radiolabeling reagents were performed only by animal biodistribution studies, and the present pharmacokinetic analyses would be useful for screening of newly designed reagents for protein radiopharmaceuticals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / chemistry
  • Albumins / pharmacokinetics
  • Animals
  • Chelating Agents / chemistry*
  • Chelating Agents / pharmacokinetics*
  • Edetic Acid / analogs & derivatives
  • Edetic Acid / chemistry
  • Edetic Acid / pharmacokinetics
  • Indium Radioisotopes
  • Isotope Labeling / methods*
  • Liver / metabolism
  • Male
  • Maleimides / chemistry
  • Maleimides / pharmacokinetics
  • Mathematical Computing
  • Mice
  • Mice, Inbred Strains
  • Models, Biological*
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacokinetics
  • Proteins / chemical synthesis*
  • Proteins / pharmacokinetics*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics*

Substances

  • Albumins
  • Chelating Agents
  • Indium Radioisotopes
  • Maleimides
  • Organometallic Compounds
  • Proteins
  • Radiopharmaceuticals
  • galactosyl-neoglycoalbumin
  • indium 1-(4-isothiocyanatobenzyl)ethylenediaminetetraacetic acid
  • 1-(4-(5-maleimidopentyl)aminobenzyl)ethylenediaminetetraacetic acid
  • Edetic Acid