title: Radioimmunolocalization of metastatic breast carcinoma using indium-111-methyl benzyl DTPA BrE-3 monoclonal antibody: phase I study.
abstract: Pharmacokinetics of radiolabeled BrE3 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 T1/2 alpha = 9.5 +/- 2.7 hr and T1/2 beta = 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.
authors.affiliation: Kaplan Comprehensive Cancer Center, Department of Pathology, NYU Medical Center/Bellevue Hospital Center, New York 10016.
authors.forename: E L
authors.initials: EL
authors.lastname: Kramer
authors.forename: S J
authors.initials: SJ
authors.lastname: DeNardo
authors.forename: L
authors.initials: L
authors.lastname: Liebes
authors.forename: L A
authors.initials: LA
authors.lastname: Kroger
authors.forename: M E
authors.initials: ME
authors.lastname: Noz
authors.forename: H
authors.initials: H
authors.lastname: Mizrachi
authors.forename: Q A
authors.initials: QA
authors.lastname: Salako
authors.forename: P
authors.initials: P
authors.lastname: Furmanski
authors.forename: S D
authors.initials: SD
authors.lastname: Glenn
authors.forename: G L
authors.initials: GL
authors.lastname: DeNardo
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D002614:Chelating Agents; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D008875:Middle Aged; D009362:Neoplasm Metastasis; D004369:Pentetic Acid / Q000031:analogs & derivatives*; D016719:Radioimmunodetection; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D007205:Indium Radioisotopes; C077295:2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid; D004369:Pentetic Acid