Intraperitoneal immunoconjugates

Journal Article · Thu Feb 01 00:00:00 EST 1990 · Cancer Research; (USA)

OSTI ID:6993396

Griffin, T W; Collins, J; Bokhari, F; Stochl, M; Brill, A B; Ito, T; Emond, G; Sands, H ^[1]

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1. 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), Vol. 50; ISSN 0008-5472
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
MONOCLONAL ANTIBODIES
TISSUE DISTRIBUTION
NEOPLASMS
RADIOIMMUNOTHERAPY
TRANSFERRIN
RECEPTORS
EXPERIMENTAL NEOPLASMS
INDIUM 111
INTRAPERITONEAL INJECTION
INTRAVENOUS INJECTION
IODINE 125
IODINE 131
MICE
YTTRIUM 90
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DISEASES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
GLOBULINS
GLOBULINS-BETA
HOURS LIVING RADIOISOTOPES
IMMUNOLOGY
IMMUNOTHERAPY
INDIUM ISOTOPES
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MAMMALS
MEDICINE
MEMBRANE PROTEINS
METALLOPROTEINS
MINUTES LIVING RADIOISOTOPES
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOIMMUNOLOGY
RADIOISOTOPES
RADIOLOGY
RADIOTHERAPY
RODENTS
THERAPY
VERTEBRATES
YTTRIUM ISOTOPES
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