Microdistribution of specific rat monoclonal antibodies to mouse tissues and human tumor xenografts

Journal Article · Fri Mar 01 04:00:00 EST 1991 · Cancer Research; (USA)

OSTI ID:5960017

Kennel, S J; Falcioni, R; Wesley, J W ^[1]

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1. Oak Ridge National Laboratory, TN (USA)

Detailed evaluations of the microdistribution of 125I-labeled monoclonal antibodies (MoAbs) to normal tissue antigens were conducted in BALB/c mice. MoAb 273-34A, which binds to a target molecule on the lumenal surface of lung endothelial cells, localizes quickly and efficiently throughout the lung vasculature. MoAb 133-13A, which binds to an antigen on macrophage-like cells expressed in nearly equal amounts in lung, liver, and spleen, localizes most efficiently to spleen and less well to liver and lung. The microdistribution of MoAb 133-13A in liver and spleen is consistent with the antigen distribution in these organs, but in the lung a more diffuse microdistribution is observed, indicating poor access of MoAb to the antigen-positive alveolar macrophages. These findings are consistent with the hypothesis that tight endothelium (lung) represents a significant barrier to extravasation of MoAb into tissue while fenestrated (spleen) and sinusoidal (liver) endothelium are more easily penetrated. In human tumor bearing nu/nu mice, the microdistribution of MoAb to the beta 4 and alpha 6 subunits of integrin was studied. These MoAbs do not cross-react with murine integrins and thus are tumor-specific in the nu/nu mouse model. Localization of 125I-labeled MoAb 450-11A, which reacts with an intercellular domain of beta 4 integrin, is very weak and diffuse. All MoAbs to extracellular domains localize well to the tumor. Microdistribution of these MoAbs in the 3 different tumors is nonuniform with heavy distribution near the blood vessels, whereas antigen distribution as determined by immunoperoxidase shows a much more uniform pattern throughout the tumors. In experiments with 125I-labeled MoAb 439-9B F(ab')2, the nonuniform pattern of distribution was not changed. Gross and microdistribution of different doses of 125I-labeled MoAb 439-9B were studied.

• OSTI ID: 5960017
• Journal Information: Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 51:5; ISSN CNREA; ISSN 0008-5472
• Country of Publication: United States
• Language: English

Related Subjects

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62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ANTIBODIES
ANTIGENS
BETA DECAY RADIOISOTOPES
BODY
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
ENDOTHELIUM
EXPERIMENTAL NEOPLASMS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
MACROPHAGES
MAMMALS
MAN
MICE
MONOCLONAL ANTIBODIES
NUCLEI
ODD-EVEN NUCLEI
PHAGOCYTES
PRIMATES
RADIOISOTOPES
RATS
RODENTS
SOMATIC CELLS
TISSUE DISTRIBUTION
TISSUES
VERTEBRATES