Initial Clinical Evaluation of Radiolabeled MX-DTPA Humanized BrE-3 Antibody in Patients with Advanced Breast Cancer1

To evaluate radiometal-babeled humanized BrE-3 (huBrE-3) monocbonal antibody as a radioimmunolocalization and therapeutic agent in breast cancer patients, tumor localization, phannacokinetics, radiation dosimetry, and immunogenicity of “ ‘In-labeled combined 1-p-isothiocyanatobenzyl 3-methyland 1-p-isothiocyanatobenzyl 4-methyldiethylenetriamine pentaacetic acid (MX-DTPA) huBrE-3 were studied. Seven women with BrE-3 antigen-positive, metastatic breast carcinoma underwent 111In huBrE-3 infusion (5 mCi; 50 mg), followed by serial gamma camera imaging and pbasma sampling. Region of interest analysis of images was used to make radiation absorbed dose estimates for ‘11In huBrE-3. Data were extrapolated to “#{176}Y huBrE-3. Human anti-human antibody (HAHA) response was measured in serum samples obtained up to 3 months after infusion. Patients tolerated infusions weib. Seventy-six percent of 105 known sites of disease were identified on planar and single-photon emission computed tomography scans. For six of seven patients, a biexponential modeb fit the pbasma timeactivity curve best with an average T112a 10.6 ± 8.5 (SD) h and average T112 1 14.2 ± 39.2 h. Radiation absorbed dose estimates for ‘ ‘ ‘In huBrE-3 for whole body averaged O.53±.08 rads/mCi. Dose estimates for ‘ #{176}YhuBrE-3 for marrow averaged 8.4 ± 11.9 rads/mCi, and for tumors, 70 ± 31.5 rads/mCi. Liver radioactivity uptake averaged Received 10/9/97; revised 4/7/98; accepted 4/7/98. The costs of pubbication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. ‘ Supported by National Cancer Institute Grant CA61455. Research at the Cancer Research Institute of Contra Costa was partially supported by a generous donation of the J. M. Long Foundation. 2 To whom requests for reprints should be addressed. at Division of Nuclear Medicine, Room HW215, NYU Medical Center. 560 First Avenue, New York, NY 10016. Phone: (212) 263-7410: Fax: (212) 2637519. 19.7 ± 8.8% injected dose at 24 h after infusion, translating into an average radiation absorbed dose 21.1 ± 12 rads/’1#{176}Y mCi administered. Only one of seven patients demonstrated a low bevel of HAHA response. Although the plasma half-lives are longer and marrow dose higher for radiolabebed huBrE-3 compared with the murine construct, the excellent tumor localization, good tumor dosimetry, and low immunogenicity support the use of #{176}Y-huBrE-3 antibody for radioimmunotherapy of breast cancer.