Radioimmunoimaging Application Of Lung Tumors And Radionuclide Radiation Therapy Of Experimental Research

Two murine anti-human lung cancer hybridomas were produced by using the cell fusion technique. Both monoclonal antibodies, named AM-7 and SM-1, were found to belong to IgG1 subclass, with the affinity constant (Ka) of 1.4 × 10⁹ L.mol^-1 and 1.12 × 10⁹ L.mol^-1 respectively Immunochemical and immunopathological studies showed that AM-7 reacted strongly with the lung adenocarcinoma and squamous carcinoma, whereas SM-1 reacted with squamous carcinoma, SCLC and lung giant cell cancer. The reactive rate of all specimens was 78.5% using a single McAb but a higher rate, about 92%, could be achieved with the use of a mixture of McAbs, although the specific tumor binding of McAb was not increased.Four methods of enzymatic cleavage of purified McAbs were carried out and compared . The ficin and bromelain were superior to papain and pepsin, because the former gave a higher yield as well as a higher residual immunoreactivity of fragments and required a shorter digestive time.The McAbs and their fragments were radiolabeled with radioiodine and Tc-99m. Biodistribution of both McAbs demonstrated that T/NT ratios were more than 1.5 at 24 hr and more than 2.5 at 48 hr in most tissues, while higher ratios were achieved at 72 hr. A clear scintigraphic image of human cancer xenograft was visualized in 48-72 hrs. The fragments showed more rapid distribution and higher T/NT ratios in comparison with the intact IgG, so the imaging of tumor xenografts could be performed earlier.I-131 and Tc-99m labeled McAbs were administered to 22 patients suspected of having lung cancer and the foci were imaged with a SPECT. Sixteen of 21 cases of primary lung cancer were detected (75% sensitivity). One patient suffering from benign disease gave a negative result. No false positive was seen, so the specificity was 100%.⁹⁰ Y was produced by a ⁹⁰Sr⁹⁰Y generator made by ourselves. After mixing thoroughly with Bio-Rex 70 resin, it was given by hepatic artery catherization to one lobe of dog's liver. A very distinct necrosis was observed in the region of ⁹⁰Y deposition after two weeks. This preliminary finding suggests that ⁹⁰Y labeled resin may possibly be a useful agent in the treatment of tumors.