Cationization of immunoglobulin G results in enhanced organ uptake of the protein after intravenous administration in rats and primate

Journal Article · Mon Jul 01 04:00:00 EDT 1991 · Journal of Pharmacology and Experimental Therapeutics; (United States)

OSTI ID:5451762

Triguero, D; Buciak, J L; Pardridge, W M ^[1]

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1. Department of Medicine, University of California, Los Angeles School of Medicine (USA)

Cationization of proteins in general enhances the cellular uptake of these macromolecules, and cationized antibodies are known to retain antigen binding properties. Therefore, cationized antibodies may be therapeutic and allow for intracellular immunization. The present studies test the hypothesis that the tissue uptake of cationized immunoglobulin G (IgG) after intravenous administration may be greatly increased relative to the uptake of native proteins. The pharmacokinetics of cationized immunoglobulin G clearance from blood, and the volume of distribution of the cationized or native protein (albumin, IgG) for 10 organs was measured both in anesthetized rats and in an anesthetized adult Macaca irus cynomologous monkey. Initial studies on brain showed that serum factors inhibited uptake of 125I-cationized IgG, but not 3H-cationized IgG. The blood-brain barrier permeability surface area product for 3H-cationized IgG was 0.57 {plus minus} 0.04 microliters min-1 g-1. The ratio of the volume of distribution of the 3-H-cationized IgG compared to 3H-labeled native albumin ranged from 0.9 (testis) to 15.7 (spleen) in the rat at 3 hr after injection, and a similarly enhanced organ uptake was observed in the primate. In conclusion, these studies demonstrate that cationization of immunoglobulin greatly increases organ uptake of the plasma protein compared to native immunoglobulins, and suggest that cationization of monoclonal antibodies may represent a potential new strategy for enhancing the intracellular delivery of these proteins.

• OSTI ID: 5451762
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (United States), Journal Name: Journal of Pharmacology and Experimental Therapeutics; (United States) Vol. 258:1; ISSN JPETA; ISSN 0022-3565
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALBUMINS
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BLOOD-PLASMA CLEARANCE
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CLEARANCE
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
GLOBULINS
HYDROGEN COMPOUNDS
IMMUNOGLOBULINS
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
INTRAVENOUS INJECTION
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MACACUS
MAMMALS
MONKEYS
MONOCLONAL ANTIBODIES
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PRIMATES
PROTEINS
RADIOISOTOPES
RATS
RODENTS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES