Radioimmunolocalization of metastatic breast carcinoma using indium-111- methyl benzyl DTPA BrE-3 monoclonal antibody: Phase I study

Pharmacokinetics of radiolabeled BrE-3 monoclonal antibody (Mab), reactive against a breast mucin epitope, were assessed in 15 patients with advanced breast cancer. Patients received 5 mCi (185 MBq) of ¹¹¹In-methyl benzyl isothiocyanate DTPA (MX-DTPA) conjugated BrE-3 Mab intravenously with total antibody doses of 10, 50 or 100 mg. Serial quantitative imaging, blood and urine clearance were obtained to measure pharmacokinetics, assess tumor localization and estimate radiation dose. Organ function was followed to determine toxicity. Mild allergic reactions occurred in four patients. Eighty-six percent of 70 known lesions and 5 unsuspected lesions were detected by antibody imaging. Biexponential modeling of radiolabeled antibody in serum showed a T( 1/2 (α)) = 9.5 ± 2.7 hr and T( 1/2 (β)) = 56 ± 25.4 hr. Total urinary excretion averaged 35.5% ± 19.3% injected dose (ID) by Day 8. Quantitative imaging showed that 0.02-2.56%ID localized in tumors. Extrapolating dosimetry from ¹¹¹In-MX-DTPA-BrE-3 to ⁹⁰Y-MX-DTPA-BrE-3, we estimate therapeutic radiation doses could be delivered to some tumors with tolerable toxicity.