Pharmacokinetic evaluation of technetium-99-metallothionein-conjugated mouse monoclonal antibody B72. 3 in rhesus monkeys

Journal Article · Tue Aug 01 04:00:00 EDT 1989 · Journal of Nuclear Medicine; (USA)

OSTI ID:5477275

Burchiel, S W; Hadjian, R A; Hladik, W B; Drozynski, C A; Tolman, G L; Haber, S B; Gallagher, B M ^[1]

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1. Univ. of New Mexico College of Pharmacy, Albuquerque (USA)

These studies were conducted to determine the biodistribution and pharmacokinetics of ({sup 99m}Tc)metallothionein-conjugated B72.3 ((Tc)MT-B72.3) in Rhesus monkeys (Macaca mulatta) that were performed as part of the preclinical evaluation of (Tc)MT-B72.3. The B72.3-MT conjugate was studied at three doses of B72.3 ranging from 0.03 mg/kg to 1 mg/kg to determine whether a relationship existed between the dose of total antibody administered intravenously and the biodistribution and clearance of the radiolabeled protein. Results indicated that (Tc)MT-B72.3 distributes rapidly to central body cavity organs and that there was no difference in the rate of blood elimination for the three doses of B72.3 studied. The terminal phase of blood elimination was found to be 26.2 +/- 6.1 hr for the combined groups of monkeys. Approximately one-half of injected {sup 99m}Tc activity was recovered in the urine within 24 hr. A second purpose of these studies was to evaluate the overall immunogenicity of the mouse monoclonal B72.3 IgG1 antibody in Rhesus monkeys. These results demonstrated that a single i.v. exposure to mouse monoclonal B72.3 at doses of 0.3 mg/kg or greater elicited antibody production to B72.3 in Rhesus monkeys within 3 wk. Analysis of (Tc)MT-B72.3 biodistribution and clearance in monkeys with circulating levels of antibodies to B72.3 (immunized monkeys) revealed that the liver was the primary site of clearance of the presumed immune complex and that blood elimination was greatly accelerated.

• OSTI ID: 5477275
• Journal Information: Journal of Nuclear Medicine; (USA), Journal Name: Journal of Nuclear Medicine; (USA) Vol. 30:8; ISSN 0161-5505; ISSN JNMEA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
ANTIBODIES
ANTIBODY FORMATION
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
DISTRIBUTION
DRUGS
EVALUATION
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
ISOMERIC NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MAMMALS
METALLOPROTEINS
METALLOTHIONEIN
MICE
MONKEYS
MONOCLONAL ANTIBODIES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANOMETALLIC COMPOUNDS
PRIMATES
PROTEINS
RADIOISOTOPES
RADIOPHARMACEUTICALS
REACTION KINETICS
RODENTS
TECHNETIUM 99
TECHNETIUM ISOTOPES
TISSUE DISTRIBUTION
VERTEBRATES
YEARS LIVING RADIOISOTOPES