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Imaging and Phase I Study of ¹¹¹In- and ⁹⁰Y-labeled Anti-Lewis^Y Monoclonal Antibody B3

Laboratory of Molecular Biology [L. H. P-S., I. P.], Department of Nuclear Medicine, Warren G. Magnuson Clinical Cancer Center [J. A. C., C. P., M. W.], Medicine Branch [D. P., M. H., C. A.], Chemistry Section, ROB [O. G., M. B.], National Cancer Institute, NIH, Bethesda, Maryland 20892; Food and Drug Administration, Bethesda, Maryland 20892 [K. W.]; and Department of Pathology, Wake Forest University, Winston-Salem, North Carolina 27157 [M. C. W.]

B3 is a murine monoclonal antibody (mAb) that recognizes a Lewis^Y carbohydrate antigen present on the surface of many carcinomas. An imaging and Phase I trial was performed to study the ability of ¹¹¹In-mAb B3 to image known metastasis and determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), kinetics, and biodistribution of ⁹⁰Y-mAb B3. Patients (n = 26) with advanced epithelial tumors that express the Lewis^Y antigen were entered. All patients received 5 mCi of ¹¹¹In-mAb B3 for imaging. ⁹⁰Y-mAb B3 doses were escalated from 5 to 25 mCi in 5-mCi increments. ¹¹¹In-mAb B3 and ⁹⁰Y-mAb B3 were coadministered over a 1-h infusion. Definite tumor imaging was observed in 20 of 26 patients. Sites imaged included lung, liver, bone, and soft tissues. The MTD of ⁹⁰Y-mAb B3 was determined to be 20 mCi. The DLTs were neutropenia and thrombocytopenia. Tumor doses ranged from 7.7 to 65.1 rad/mCi. ¹¹¹In- and ⁹⁰Y-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 pharmacokinetics. Bone marrow biopsies (n = 23) showed 0.0038 ± 0.0016% of injected dose/gram for ¹¹¹In-mAb B3 compared to 0.0046 ± 0.0017% of injected dose/gram for ⁹⁰Y-mAb B3 (P = 0.009). When given to patients with carcinomas that express the Lewis^Y antigen, ¹¹¹In-mAb B3 demonstrated good tumor localization. The MTD of ⁹⁰Y-mAb B3 is 20 mCi, with myelosuppression as the DLT. Higher doses of radioactivity need to be delivered to achieve an antitumor effect. Humanized mAb B3 is being developed for evaluation in radioimmunotherapy. A clinical trial to explore the use of higher doses of ⁹⁰Y-mAb B3 with autologous stem cell support is planned.

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