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Monoclonal Antibody Targeting of Liposomes to Mouse Lung in Vivo¹

Department of Biochemistry, University of Tennessee, Knoxville, Tennessee 37996-0840 [B. J. H., S. K., L. H.], and Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-8077 [S. K., R. L.]

A monoclonal antibody (MoAb), 273-34A, specifically binds to an epitope expressed almost exclusively on capillary endothelial cells of the lung. Within 15 min after i.v. injection, approximately 80 to 85% of the injected radioiodinated MoAb 273-34A accumulates in the lung. Approximately 90 to 95% of the recovered dose is found in the lung for up to 1 week postinjection. Ratios of MoAb 273-34A to a nonspecific, irrelevant MoAb 135-14 are 250 to 285 times higher in the lung than in the serum. When 273-34A was coupled with palmitic acid and incorporated into liposomes, the amount of ¹²⁵I-labeled liposomes recovered per g of tissue was 12 times higher in the lung than in the liver at 15 min postinjection, and 22 times higher at 5 h postinjection. At 24 h postinjection the amount of liposomes per gram of lung tissue was still 6.0 times the amount per gram of liver tissue. Liposomes conjugated to MoAb 273-34A locate in the lung 20 and 15 times better than do liposomes conjugated to the nonspecific MoAb 135-14 at 15 min and 24 h postinjection, respectively. The results indicate that this immunoliposome system could be used as a model for enhanced drug delivery to the lung. The potential use for delivering anticancer drugs for therapy of lung tumors is discussed.

¹ This work was sponsored jointly by Grants CA 24553 and AI 25834 from the NIH to L. H., and by the Office of Health and Environmental Research, United States Department of Energy, under Contract DE-AC05-84OR21400 with the Martin Marietta Energy Systems, Inc.

² To whom requests for reprints should be addressed.

Received 1/26/89. Revised 6/12/89. Revised 8/ 8/89. Accepted 8/16/89.

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