This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Beatty, B. G. Articles by Beatty, J. D. Search for Related Content PubMed PubMed Citation Articles by Beatty, B. G. Articles by Beatty, J. D.

Mechanism of Decreasing Liver Uptake of ¹¹¹In-labeled Anti-Carcinoembryonic Antigen Monoclonal Antibody by Specific Antibody Pretreatment in Tumor Bearing Mice¹

City of Hope National Medical Center, Department of General and Oncologic Surgery, and Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010

The purpose of this study was to examine the mechanism of specific antibody pretreatment for reduction of liver uptake of ¹¹¹In-labeled monoclonal antibody (MAB). Previous work with an anti-carcinoembryonic antigen (CEA) MAB (T84.66) and LS174T human colon cancer xenografts in nude mice has shown that giving a high dose (0.2 mg) of unlabeled T84.66 in conjunction with the same MAB (T84.66) labeled with ¹¹¹In (Indacea) significantly lowered the liver uptake of ¹¹¹In.

High performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis were used to assess the radiolabeled components in serum and liver at different times following administration of Indacea in normal and tumor bearing mice. In serum the ¹¹¹In remained associated with the IgG in both tumor bearing and non-tumor bearing mice. Liver uptake of ¹¹¹In in mice without tumor was low (8–12% injected dose/g) and both IgG and a low molecular weight metabolite were found in the liver homogenates. Liver uptake in tumor bearing mice increased dramatically (15–40% injected dose/g) with size of tumor and in addition to the IgG and low molecular weight components, a high molecular weight compound was identified. Administration of CEA:Indacea complexes to non-tumor bearing mice produced the same high pressure liquid chromatography and gel patterns as those seen in mice with large (>1 g) tumors. Liver homogenates from tumor bearing mice given specific antibody pretreatment showed the same patterns seen with non-tumor bearing mice (no high molecular weight peak). In conclusion, CEA:Indacea complexes are formed in tumor bearing mice and rapidly cleared by the liver. Specific antibody pretreatment results in the production of unlabeled CEA:MAB complexes causing a reduction in the formation of CEA:Indacea complexes and a lower liver uptake of ¹¹¹In.