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S J Adelstein

Publications and source records attributed to S J Adelstein.

159 records · Page 9Linked to original sources
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Radiotoxicity of 5-[125I]iodo-2'-deoxyuridine in mammalian cells following treatment with 5-fluoro-2'-deoxyuridine.

We have enhanced the uptake of 5-[125I]iodo-2'-deoxyuridine (125IUdR) in Chinese hamster V79 cells with 5-fluoro-2'-deoxyuridine (FUdR) and have examined the combined toxicity of these agents. Although the uptake of 125IUdR increases approximately 3.2 +/- 0.5-fold in the presence of 1 microM FUdR, when cell survival fraction is plotted as a function of intranuclear 125IUdR content, the biphasic curve obtained reaches a plateau at a higher survival fraction than with control cells not exposed to FUdR. The results suggest that a greater number of cells were prevented from entering the S phase and consequently from incorporating 125IUdR. An FUdR- 125IUdR combination, therefore, does not seem to enhance the therapeutic potential of 125IUdR. Such observations are also of importance when FUdR and other inhibitors are used to enhance cold IUdR uptake in an effort to obtain an increase in radiosensitization effects.

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Capping and internalization of a monoclonal antibody-surface antigen complex: a possible mode of interaction of monoclonal antibodies and tumor cells.

Our results demonstrate that upon incubation of 125I-3G5 (a monoclonal IgM against a membrane ganglioside antigen on RINm5F cells) with rat insulinoma RINm5F cell monolayers at 37 degrees C, the IgM is rapidly internalized. Cell-bound radioactivity, detectable within 10 to 15 minutes, reaches a peak at 4 hours. By 24 hours the intracellular radioactivity has decreased to about 37.5% of the 4-hour value, accompanied by an increase in free 125I in the incubation medium. The incubation of 125I-3G5 with RINm5F cell monolayers at 4 degrees C shows that this series of events is inhibited by low temperature. Microautoradiography confirms these events indicating the presence of radiolabeled antibody on the plasma membrane as well as distinct capping processes and diffuse radioactive deposits within the cells as early as 5 to 10 minutes after initiating incubation at 37 degrees C. Electron microscopy autoradiography provides a detailed demonstration of the capping phenomenon and of endocytic vacuoles, followed at later times by the distribution of radioactive deposits throughout the cell. This model constituted by the capping of the 125I-3G5-ganglioside complex on rat insulinoma RINm5F cells may be useful in elucidating a possible mode of interaction of monoclonal antibodies and tumor cells.

Animals↗
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Preadsorption of radiolabeled monoclonal antibodies to liver and spleen tissues leads to higher tumor-to-normal-tissue ratios.

This study addresses the impact of background activity on the use of radioimmunoconjugates for radioimmunodiagnosis and radioimmunotherapy. Since the liver and the spleen represent organs with preferential nonspecific uptake, we exposed radiolabeled (iodinated and Indium-111 labeled) preparations of monoclonal antibodies to a suspension of fresh liver and spleen cells at physiological temperature and compared their immunoreactivity, in vivo biodistribution, and tumor targeting to those of the same radiolabeled proteins without prior adsorption to this suspension. The biodistribution studies were performed under conditions of high background activity, i.e., shortly after the injection (1 hour) and using a high dose of the protein. Preadsorption of radiolabeled monoclonal antibodies results in a significant decreased uptake in certain normal tissues, i.e., greater contrast between normal and tumor tissues, as demonstrated by the quotient of the two target-to-nontarget ratios (exposed/unexposed antibody) which was greater than one for most of the tissues examined.

Adsorption↗