Clinical pharmacology and tissue disposition studies of 131I-labeled anticolorectal carcinoma human monoclonal antibody LiCO 16.88.
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.
Rosenblum
M G
MG
Department of Clinical Immunology and Biological Therapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Levin
B
B
Roh
M
M
Hohn
D
D
McCabe
R
R
Thompson
L
L
Cheung
L
L
Murray
J L
JL
D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D015179:Colorectal Neoplasms / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000378:metabolism; D016499:Radioimmunotherapy; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D007457:Iodine Radioisotopes