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The targeting of monoclonal antibodies to human tumor xenografts in nude mice was investigated by analysis of the cellular distribution of two radioiodinated monoclonal antibodies, B6.2 and B72.3, which recognize different tumor-associated antigens. The time course of distribution of each antibody within Clouser human mammary carcinoma (B6.2 positive, B72.3 negative) and LS174T human colorectal carcinoma (B6.2 positive, B72.3 positive) following i.v. injections was compared using autoradiographic techniques, which were also used to determine the pattern of binding after in vitro incubation with radiolabeled antibody. Both in vivo and in vitro localization of 125I-B72.3 in LS174T were characterized by the binding of antibody to antigen-rich mucin globules. In contrast, in vivo localization of B6.2 was restricted to groups of cells in well vascularized regions. Thus, the in vivo accumulations of B6.2 and B72.3 although quantitatively similar showed very different spatial distributions within LS174T tumors. The in vivo binding of B6.2 in Clouser tumors was restricted to small clusters of cells scattered fairly evenly throughout the tumor. There was no evidence for the presence of such antigen-rich foci after in vitro incubation of tumor sections with B6.2 suggesting that heterogeneity of regional uptake may be due to differences in antibody delivery. This type of information may provide a rational basis for the selection of appropriate therapeutic isotopes for radioimmunotherapy studies using these and other tumor models.

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Cyclic AMP levels and protein kinase activity were determined in the aortas of rats with normotension, moderate and severe spontaneous hypertension. While the cyclic AMP levels were reduced in the aortas from rats with moderate and severe hypertension the protein kinase levels were found to be elevated only in the aortas from rats with severe hypertension. We have grown in tissue culture, aortic smooth muscle cells from the normotensive and severely hypertensive rat. Cultured cells from both strains have similar growth patterns and morphology. The differences seen in cyclic AMP and protein kinase levels in the intact aortas are also seen in the aortic smooth muscle cells in culture.