Pharmacokinetics of /sup 111/In-labeled anti-p97 monoclonal antibody in patients with metastatic malignant melanoma

Journal Article · Wed May 01 04:00:00 EDT 1985 · Cancer Res.; (United States)

OSTI ID:5267276

Rosenblum, M G; Murray, J L; Haynie, T P; Glenn, H J; Jahns, M F; Benjamin, R S; Frincke, J M; Carlo, D J; Hersh, E M

Twenty-eight patients with metastatic malignant melanoma received anti-p97 murine monoclonal antibody (96.5) infused over 2 h at doses between 1 and 20 mg coupled to either 2.5 or 5.0 mCi of /sup 111/In by the bifunctional chelating agent diethyltriaminepentaacetic acid. Clearance of /sup 111/In from plasma closely fit an open, one-compartment mathematical model (r2 greater than 0.90). The overall half-life of /sup 111/In plasma was approximately 31 h and did not appear to be dependent on the total dose of antibody administered. The apparent volume of distribution of the /sup 111/In label approximated the total blood volume (7.8 +/- 0.7 liters) at the 1-mg dose and decreased to 3.0 +/- 0.14 liters at the 20-mg dose, suggesting saturation of antigenic or other extravascular binding sites at higher antibody doses. The clearance of the murine monoclonal antibody itself from plasma was measured by an enzyme-linked immunosorbent assay. The pharmacokinetics for the murine antibody in plasma also fit an open, one-compartment mathematical model. All pharmacokinetic parameters for unlabeled antibody closely paralleled those found for /sup 111/In-labeled antibody pharmacokinetics. This suggests that the /sup 111/In radiolabel remains complexed to the monoclonal antibody after in vivo administration. The cumulative urinary excretion of the /sup 111/In label over 48 h was between 12 and 23% of the total administered dose and is assumed to represent /sup 111/In-labeled chelate complex unattached to antibody. Analysis of the /sup 111/In label in spleen, liver, heart, and kidney showed that the concentration of label in liver tissue was reduced with increasing antibody doses and coincided with changes in the apparent volume of distribution.

• Research Organization: Univ. of Texas System Cancer Center, Houston
• OSTI ID: 5267276
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 5; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETIC ACID
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
BIOLOGICAL MATERIALS
BLOOD
BLOOD-PLASMA CLEARANCE
BODY
BODY FLUIDS
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
CHELATING AGENTS
CHEMICAL BONDS
CLEARANCE
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
DOSES
ELECTRON CAPTURE RADIOISOTOPES
EXCRETION
GLANDS
HEART
INDIUM 111
INDIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
KINETICS
LABELLED COMPOUNDS
LIVER
MAMMALS
MATERIALS
MATHEMATICAL MODELS
MELANOMAS
METASTASES
MICE
MINUTES LIVING RADIOISOTOPES
MONOCARBOXYLIC ACIDS
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATIENTS
RADIATION DOSES
RADIOISOTOPES
REACTION KINETICS
RODENTS
SPLEEN
TRACER TECHNIQUES
VERTEBRATES