Biodistribution and radioimmunotherapy of human breast cancer xenografts with radiometal-labeled DOTA conjugated anti-HER2/neu antibody 4D5.

摘要: HER2/neu oncogene encodes a 185 kDa trans-membrane protein which is overexpressed in 20-30% of breast and ovarian cancers portends poor prognosis. We have studied the targeting therapy this oncoprotein with 4D5, murine monoclonal antibody recognizes distinct epitope on extracelluar domain HER2/neu. conjugated an active ester macrocyclic chelating agent DOTA, radiolabeled conjugate either (111)In or (90)Y, distribution therapy, respectively, athymic mice bearing xenografts MCF7/HER2/neu, human cancer cell line transfected oncogene. For biodistribution (111)In-labeled DOTA-4D5, high specificity tumor localization (30% ID/g) was seen tumor-to-blood ratio greater than 2 at 48 h postinjection. Compared to previously published study (125)I-labeled 4D5 beige nude NIH3T3/HER2/neu [De Santes et al. (1992) Cancer Res. 52, 1916-1923], gave superior uptake ID/g vs 17% 48h). In study, treatment MCF7/HER2/neu 100 microCi (3 microg) (90)Y-labeled DOTA-4D5 caused 3-fold reduction growth compared untreated controls (injected serum albumin) 40 days. Treatment animals nonspecific DOTA-Leu16 had no inhibition. unlabeled slight effect controls. When analyzed level single animals, seven nine animals; however, two inhibition observed. Although cold therapeutic unexpected dose microg), it may be possible that some 3 microg augmented reduction. To further explore effects alone, were treated 400 administered doses. These showed 1.7-1.8-fold over 28 days, result less obtained RIT only.