Effect of tumor mass and antigenic nature on the biodistribution of labeled monoclonal antibodies in mice

Journal Article · Thu Jun 01 04:00:00 EDT 1989 · Cancer Res.; (United States)

OSTI ID:5931483

Watanabe, Y; Endo, K; Koizumi, M; Kawamura, Y; Saga, T; Sakahara, H; Kuroki, M; Matsuoka, Y; Konishi, J

The effect of tumor mass and antigenic nature on the biodistribution of 111In- and 125I-labeled monoclonal antibodies (MoAbs) was studied using F(ab')2 fragments of three representative anti-tumor MoAbs and SW1116 human colorectal carcinoma grown in nude mice. The 19-9, F33-104 anti-CEA, and 17-1A MoAbs showed specific binding to SW1116 cells. The former two MoAbs recognize circulating CA 19-9 with molecular weights of more than 5,000,000 and CEA of Mr 170,000-180,000, respectively, whereas 17-1A reacts with a nonshedding antigen. Both percentage injected dose per gram tumor and tumor-to-blood ratios were inversely proportional to the tumor mass in nude mice administered 111In- and 125I-labeled 19-9, but liver uptake increased as tumor size increased. Analysis of serum samples and tumor homogenates demonstrated the presence of a high-molecular-weight species, probably due to the antibody binding to CA 19-9. In the case of 111In-labeled anti-CEA MoAb, tumor uptake also decreased and liver uptake increased with tumor size, but this effect was less obvious than that of 19-9. In contrast, tumor and liver uptake of 125I-labeled anti-CEA MoAb, 111In- and 125I-labeled 17-1A and control antibodies were independent of tumor mass. The absolute tumor uptake and tumor-to-blood ratios of all 125I-labeled antibodies were lower than those of the 111In-labeled ones. And the effect of tumor mass was also weaker with 125I-labeled antibodies, probably due to in vivo dehalogenation. These results indicate that the effect of tumor size on the incorporation of labeled MoAb into tumors is dependent on the antigenic nature to be targeted and/or radionuclides used for labeling and that high concentrations of circulating high molecular weight antigens may limit in vivo use of MoAb conjugates.

• Research Organization: Kyoto Univ. Hospital (Japan)
• OSTI ID: 5931483
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 49:11; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
550604 -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMALS
ANTIBODIES
ANTIGENS
BETA DECAY RADIOISOTOPES
BODY
CARCINOMAS
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
EXPERIMENTAL NEOPLASMS
GASTROINTESTINAL TRACT
INDIUM 111
INDIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
INTESTINES
IODINE 125
IODINE ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LARGE INTESTINE
MAMMALS
MICE
MINUTES LIVING RADIOISOTOPES
MOLECULAR WEIGHT
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANS
RADIOISOTOPES
RECTUM
RODENTS
SEPARATION PROCESSES
TISSUE DISTRIBUTION
TUMOR CELLS
VERTEBRATES