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In Vivo Biodistribution of a Humanized Anti-Lewis Y Monoclonal Antibody (hu3S193) in MCF-7 Xenografted BALB/c Nude Mice

Tumour Targeting Program, Ludwig Institute for Cancer Research, Melbourne Branch, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia [K. C., F-T. L., F. E. S., A. M. S.]; Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892-100 [M. W. B.]; Ludwig Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York 10021 [L. J. O.].

The biodistribution characteristics of a humanized anti-Lewis^y antibody (hu3S193) radiolabeled to three radioisotopes, ¹²⁵I, ¹¹¹In, and ⁹⁰Y, were examined in a BALB/c nude mouse xenograft model of breast cancer. The immunoreactivity of both ¹²⁵I- and ¹¹¹In-bound hu3S193 exceeded 50% and was 20% for ⁹⁰Y. In vivo, labeled antibody was shown by gamma camera imaging and immunohistochemical and autoradiographic techniques to localize to Lewis^y-expressing breast xenografts with minimal normal tissue uptake. Maximal radioisotope uptake peaked at 48 h for all three isotopes; however, the percentage of injected dose/gram and tumor retention were greater for ¹¹¹In- and ⁹⁰Y-bound antibody than for ¹²⁵I-bound antibody. Although immunoreactivity of ¹¹¹In- and ¹²⁵I-labeled hu3S193 in serum was stable over a 5-day period, the amount of unlabeled ¹¹¹In in serum was lower than ¹²⁵I, which together with higher tumor uptake indicates better retention of ¹¹¹In-labeled hu3S193 and catabolites within the tumor cells. Superior tumor uptake and retention of ¹¹¹In-labeled hu3S193 and similar blood clearance compared with ¹²⁵I-labeled hu3S193, suggest that radiometals are the preferred radioisotope for this antibody-antigen system. Humanized 3S193 is a promising new construct for the targeting and potential therapy of Lewis^y-expressing tumors.

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