Intraperitoneal immunoconjugates
- Univ. of Massachusetts Medical School, Worcester (USA)
Intracavitary instillation of radioantibodies has been proposed as therapy for anatomically confined malignant disease. To evaluate this therapeutic strategy, a monoclonal antibody reactive with human transferrin receptor (7D3) was evaluated for localization in a human malignant mesothelioma transplanted i.p. in athymic nude mice. This antibody was purified and labeled with 131I, 125I, or 111In. Radiolabeled antibody was administered i.p. or i.v. to tumor-bearing mice. Three h after injection, the percentage of injected dose/g (ID/g) of tumor was higher in free-floating ascites tumor cells (31.0%/g tumor cell pellet) after i.p. injection than after i.v. injection (12.0%). However, localization of radiolabel in i.p. solid tumors was similar (5.37% ID/g i.p. versus 4.73% of ID/g i.v.), and by 24 h both routes of administration produced similar localization of radiolabel in both free-floating ascites cells and solid tumors. In contrast, uptake of radiolabel into liver, kidney, and to a lesser extent bone and bone marrow, was less with i.p. than with i.v. administration. In clinical studies with 111In and 90Y antibodies administered i.p. to patients with ovarian cancer, confined biodistribution of the radioantibody was again seen, although interpatient variability of rate of egress of the radiolabel was documented. Therefore, both preclinical and clinical data indicate that i.p. therapy with immunoconjugates may be advantageous for cancer confined to the peritoneal cavity. This advantage stems primarily from reduced localization of isotope in organs of catabolism or toxicity (liver, kidney, bone, and bone marrow), rather than greatly increased levels of isotope in tumor. Unresolved problems include degree of antibody penetration into solid tumors, microdosimetry, and radioantibody effectiveness for tumor killing.
- OSTI ID:
- 6993396
- Journal Information:
- Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 50; ISSN 0008-5472; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DISEASES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
EXPERIMENTAL NEOPLASMS
GLOBULINS
GLOBULINS-BETA
HOURS LIVING RADIOISOTOPES
IMMUNOLOGY
IMMUNOTHERAPY
INDIUM 111
INDIUM ISOTOPES
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
INTRAPERITONEAL INJECTION
INTRAVENOUS INJECTION
IODINE 125
IODINE 131
IODINE ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MAMMALS
MEDICINE
MEMBRANE PROTEINS
METALLOPROTEINS
MICE
MINUTES LIVING RADIOISOTOPES
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOIMMUNOLOGY
RADIOIMMUNOTHERAPY
RADIOISOTOPES
RADIOLOGY
RADIOTHERAPY
RECEPTORS
RODENTS
THERAPY
TISSUE DISTRIBUTION
TRANSFERRIN
VERTEBRATES
YTTRIUM 90
YTTRIUM ISOTOPES