Pharmacokinetics of internally labeled monoclonal antibodies as a gold standard: comparison of biodistribution of /sup 75/Se-, /sup 111/In-, and /sup 125/I-labeled monoclonal antibodies in osteogenic sarcoma xenografts in nude mice
In order to know the true biodistribution of anti-tumor monoclonal antibodies, three monoclonal antibodies (OST6, OST7, and OST15) against human osteosarcoma and control antibody were internally labeled with 75Se by incubating (75Se)methionine and hybridoma cells. 75Se-labeled monoclonal antibodies were evaluated both in vitro and in vivo using the human osteogenic sarcoma cell line KT005, and the results were compared with those of 125I- and 111In-labeled antibodies. 75Se-, 125I- and 111In-labeled monoclonal antibodies had identical binding activities to KT005 cells, and the immunoreactivity was in the decreasing order of OST6, OST7, and OST15. On the contrary, in vivo tumor uptake (% injected dose/g) of 75Se- and 125I-labeled antibodies assessed using nude mice bearing human osteosarcoma KT005 was in the order of OST7, OST6, and OST15. In the case of 111In, the order was OST6, OST7, and OST15. High liver uptake was similarly seen with 75Se- and 111In-labeled antibodies, whereas 125I-labeled antibodies showed the lowest tumor and liver uptake. These data indicate that tumor targeting of antibody conjugates are not always predictable from cell binding studies due to the difference of blood clearance of labeled antibodies. Furthermore, biodistribution of both 111In- and 125I-labeled antibodies are not identical with internally labeled antibody. Admitting that internally labeled antibody is a ''gold standard'' of biodistribution of monoclonal antibody, high liver uptake of 111In-radiolabeled antibodies may be inherent to antibodies. Little, if any, increase in tumor-to-normal tissue ratios of antibody conjugates will be expected compared to those of 111In-labeled antibodies if stably coupled conjugates are administered i.v.
- Research Organization:
- Kyoto Univ. (Japan)
- OSTI ID:
- 6153362
- Journal Information:
- Cancer Res.; (United States), Vol. 49:7
- Country of Publication:
- United States
- Language:
- English
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TISSUE DISTRIBUTION
BIOCHEMICAL REACTION KINETICS
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HYBRIDOMAS
IMMUNE REACTIONS
INDIUM 111
IODINE 125
LIVER
METHIONINE
MICE
OSTEOSARCOMAS
SELENIUM 75
UPTAKE
AMINO ACIDS
ANIMAL CELLS
ANIMALS
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DAYS LIVING RADIOISOTOPES
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DISEASES
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
GLANDS
INDIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KINETICS
LIPOTROPIC FACTORS
MAMMALS
MINUTES LIVING RADIOISOTOPES
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SARCOMAS
SELENIUM ISOTOPES
SKELETAL DISEASES
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics
550604 - Medicine- Unsealed Radionuclides in Therapy- (1980-)