Pharmacokinetics of 111In-labeled OC-125 antibody in cancer patients compared with the 19-9 antibody.
We recently reported on the pharmacokinetics in 14 cancer patients of the 19-9 antibody radiolabeled with 111In. We have now repeated this investigation in 18 cancer patients using the OC-125 antibody, in part to compare the in vivo behavior of two murine monoclonal antibodies of the same subclass administered as the F(ab')2 fragments, by the same route and at the same dose. As in the earlier investigation, 1 mg of fragments was infused i.v., and organ quantitation was obtained for up to 72 h along with frequent blood and urine samples for chromatographic evaluation. Analysis of urine showed that activity clearance by this route amounted to 0.29%/h and consisted of labeled DTPA only in early samples and metabolic products thereafter. Analysis of serum samples often showed the presence of a high-molecular-weight species appearing within 24 h. This species is probably due to antibody binding to circulating antigen, although the percentage of circulating activity present as this species did not correlate well with circulating antigen levels. As before, organ accumulation was greatest in the liver, although levels were significantly reduced (12% compared to 20% of administered dose at 24 h, P less than 0.01). Plasma clearance was also significantly different: whereas the label in the case of the OC-125 antibody showed one-compartment clearance kinetics and remained in the plasma compartment, in the 19-9 case the label diffused to a second, unidentified compartment.
Hnatowich
D J
DJ
Department of Nuclear Medicine, University of Massachusetts Medical Center, Worcester 01655.
Gionet
M
M
Rusckowski
M
M
Siebecker
D A
DA
Roche
J
J
Shealy
D
D
Mattis
J A
JA
Wilson
J
J
McGann
J
J
Hunter
R E
RE
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D006801:Humans; D007205:Indium Radioisotopes; D007700:Kinetics; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes