Studies concerning the effect of external irradiation on localization of radiolabeled monoclonal antibody B72. 3 to human colon carcinoma xenografts

Journal Article · Wed Mar 01 04:00:00 EST 1989 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(89)90491-4· OSTI ID:6073825

Shrivastav, S; Schlom, J; Raubitschek, A; Molinolo, A; Simpson, J; Hand, P H

Recent studies in animal models involving antibody tumor targeting of hepatoma and melanoma and clinical trials involving hepatoma patients have suggested that preirradiation of tumors may enhance antibody tumor targeting. These reports led us to study the effect of external irradiation on monoclonal antibody (MAb) targeting of human carcinomas; as a model system, we used MAb B72.3 and the LS-174T human colon carcinoma xenograft in athymic mice. LS-174T tumors exposed to 300 cGy grew to approximately 93% the size of non-irradiated tumors, while those exposed to 600, 900, or 2,000 cGy were approximately 41% the size of control tumors. Splitting the 900 cGy into three 300-cGy fractions yielded a two-fold lower tumor volume compared with a single 900-cGy fraction. Histochemical evaluation of the carcinomas revealed a decrease in the number of mitoses per high power field consistent with early effects of radiation exposure. Using the avidin-biotin complex immunoperoxidase technique, carcinomas were assayed for expression of the tumor associated glycoprotein (TAG)-72, the high-molecular-weight mucin detected by MAb B72.3. No discernable variation was observed in the staining intensity among tumors in both the control and radiation treated group; that is, differences among tumors within each group were compatible with the known heterogeneous expression of TAG-72. Exposure of carcinomas to 300 or 900 cGy in a single fraction or 900 cGy split in three 300-cGy fractions did not yield a consistent or substantial enhanced localization of radiolabeled MAb B72.3 IgG or F(ab')2 to tumors. A 1.5-fold augmentation of MAb binding to tumors was observed in preirradiated mice; however, these results were not statistically significant.

• Research Organization: National Cancer Institute, Bethesda, MD (USA)
• OSTI ID: 6073825
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 16:3; ISSN IOBPD
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
ANTIBODIES
BIOLOGICAL MODELS
BODY
CARCINOMAS
DIGESTIVE SYSTEM
DISEASES
DOSES
EXPERIMENTAL NEOPLASMS
FRACTIONATED IRRADIATION
GASTROINTESTINAL TRACT
GLYCOPROTEINS
INTESTINES
IRRADIATION
LARGE INTESTINE
MAMMALS
MEDICINE
MICE
MOLECULAR WEIGHT
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIATION DOSES
RADIOLOGY
RADIOTHERAPY
RODENTS
THERAPY
UPTAKE
VERTEBRATES