Clinical pharmacology and tissue disposition studies of 131I-labeled anticolorectal carcinoma human monoclonal antibody LiCO 16.88. 1994

M G Rosenblum, and B Levin, and M Roh, and D Hohn, and R McCabe, and L Thompson, and L Cheung, and J L Murray
Department of Clinical Immunology and Biological Therapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.

Antibody LiCO 16.88 is a human IgM recognizing a 30- to 45-kDa intracytoplasmic antigen present in human adenocarcinoma cells. An 8-mg sample of antibody labeled with 5 mCi 131I was co-administered i.v. with 120 mg (three patients), 240 mg (three patients) or 480 mg (four patients) unlabeled antibody as a 4-h infusion. The plasma half-life was 24 +/- 1.2 h and the immediate apparent volume of distribution was 5.2 +/- 0.2 l at the 28-mg dose level. The plasma half-lives and the cumulative urinary excretion of radiolabel did not seem to vary significantly with increasing doses of unlabeled antibody. However, both the volume of distribution and the clearance rate from plasma increased significantly with increasing antibody dose. Uptake of antibody into tumor tissues obtained during laparotomy 8-9 days after administration varied between 0.00002% ID/g and 0.00127% ID/g. In five of seven patients, the tumor content of antibody was higher than that in adjacent normal tissue. Tumor-to-normal tissue ratios ranged from 0.8 to 10 (mean = 3.8 +/- 1.0). In general, the higher radioactivity(cpm)/g tumor was confirmed by both immunoperoxidase and autoradiography. Antibody 16.88 localizes in tumors after administration and may be considered for use in radioimmunotherapy trials.

UI MeSH Term Description Entries
D007075 Immunoglobulin M A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally was called a macroglobulin. Gamma Globulin, 19S,IgM,IgM Antibody,IgM1,IgM2,19S Gamma Globulin,Antibody, IgM
D007457 Iodine Radioisotopes Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes. Radioisotopes, Iodine
D008657 Metabolic Clearance Rate Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D015179 Colorectal Neoplasms Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI. Colorectal Cancer,Colorectal Carcinoma,Colorectal Tumors,Neoplasms, Colorectal,Cancer, Colorectal,Cancers, Colorectal,Carcinoma, Colorectal,Carcinomas, Colorectal,Colorectal Cancers,Colorectal Carcinomas,Colorectal Neoplasm,Colorectal Tumor,Neoplasm, Colorectal,Tumor, Colorectal,Tumors, Colorectal
D016499 Radioimmunotherapy Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY). Immunoradiotherapy,Immunoradiotherapies,Radioimmunotherapies

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