In vivo biodistribution of a humanized anti-Lewis Y monoclonal antibody (hu3S193) in MCF-7 xenografted BALB/c nude mice

The biodistribution characteristics of a humanized anti-Lewis(y) antibody ( hu3S193) radiolabeled to three radioisotopes, I-125, In-111, and Y-90, were examined in a BALB/c nude mouse xenograft model of breast cancer. The immu noreactivity of both I-125- and In-111-bound hu3S193 exceeded 50% and was 2 0% for Y-90. In vivo, labeled antibody was shown by gamma camera imaging an d 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 per centage of injected dose/gram and tumor retention were greater for In-111- and Y-90-bound antibody than for I-125-bound antibody. Although immunoreact ivity of In-111- and I-125-labeled hu3S193 in serum was stable over a 5-day period, the amount of unlabeled In-111 in serum was lower than I-125, whic h together with higher tumor uptake indicates better retention of In-111-la beled hu3S193 and catabolites within the tumor cells. Superior tumor uptake and retention of In-125-labeled hu3S193 and similar blood clearance compar ed with I-125-labeled hu3S193, suggest that radiometals are the preferred r adioisotope for this antibody-antigen system. Humanized 3S193 is a promisin g new construct for the targeting and potential therapy of Lewis(y)-express ing tumors.