Imaging and phase I study of In-111- and Y-90-labeled anti-Lewis(Y) monoclonal antibody B3

B3 is a murine monoclonal antibody (mAb) that recognizes a Lewis(Y) carbohy drate antigen present on the surface of many carcinomas. An imaging and Pha se I trial was performed to study the ability of In-111-mAb B3 to image kno wn metastasis and determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), kinetics, and biodistribution of Y-90-mAb B3, Patients (n = 26) with advanced epithelial tumors that express the Lewis' antigen were entered. All patients received 5 mCi of In-111-mAb B3 for imaging. Y-90-mAb B3 doses were escalated from 5 to 25 mCi in 5-mCi increments. In-111-mAb B S and Y-90-mAb B3 were coadministered over a 1-h infusion. Definite tumor i maging was observed in 20 of 26 patients. Sites imaged included lung, liver , bone, and soft tissues. The MTD of Y-90-mAb B3 was determined to be 20 mC i, The DLTs were neutropenia and thrombocytopenia, Tumor doses ranged from 7.7 to 65.1 rad/mCi. In-111- and Y-90-mAb B3 serum pharmacokinetics (n = 23 ) were found to be similar, The amount of B3 administered (5, 10, and 50 mg ) did not alter the pharmatokinetics, Bone marrow biopsies (n = 23) showed 0.0038 +/- 0.0016% of injected dose/gram for In-111-mAb B3 compared to 0.00 46 +/- 0.0017% of injected dose/gram for Y-90-mAb B3 (P = 0.009). When give n to patients with carcinomas that express the Lewis' antigen, In-111-mAb B 3 demonstrated good tumor localization. The MTD of Y-90-mAb B3 is 20 mCi, w ith myelosuppression as the DLT. Higher doses of radioactivity need to be d elivered to achieve an antitumor effect. Humanized mAb B3 is being develope d for evaluation in radioimmunotherapy. A clinical trial to explore the use of higher doses of Y-90-mAb B3 with autologous stem cell support is planne d.