title: Safety, pharmacokinetics, immunogenicity, and biodistribution of (186)Re-labeled humanized monoclonal antibody BIWA 4 (Bivatuzumab) in patients with early-stage breast cancer.
abstract: The aim of this prospective study was to evaluate the safety, pharmacokinetics, immunogenicity, and biodistribution of (186)Re-labeled humanized anti-CD44v6 monoclonal antibody (MAb( BIWA 4 (Bivatuzumab( in 9 patients with early-stage breast cancer. Radioimmunoscintigraphy (RIS( was performed within 1, 24, and 72 hours after administration. BIWA 4 concentration in plasma (ELISA and radioactivity measurements( and the development of human antihuman antibody (HAHA( responses was determined. The biodistribution of (186)Re-BIWA 4 was determined by radioactivity measurements in tumor and normal tissue biopsies obtained during surgery 1 week after administration. Administration of (186)Re-BIWA 4 was well tolerated by all patients and no HAHA responses were observed. The mean t(1/2) in plasma of BIWA 4 (ELISA( was 81 hours (range, 67-97(, whereas the mean radioactivity t(1/2) tended to be longer, at 105 hours (range, 90-114(. RIS unmistakably showed the tumor in 3 patients. Less clear identifications were established in 3 additional patients. In 2 patients, the tumor was wrongly identified in the contralateral breast. Median tumor CD44v6 expression, as determined by immunohistochemistry, was 70% (range, 10-90%). Mean tumor uptake was 2.96% ID/kg (range, 0.92-6.27(, with no apparent correlation with either tumor CD44v6 expression, tumor-cell cellularity, or tumor diameter. Tumor-to-nontumor ratios were unfavorable for blood, bone marrow, mammary gland tissue, and skin.
  
  
  CONCLUSIONS
  The (186)Re-labeled humanized MAb BIWA 4 can safely be administered to patients with early-stage breast cancer. Tumorto- nontumor ratios were unfavorable, with no apparent correlation with CD44v6 expression, tumor-cell cellularity, or tumor diameter. BIWA 4, therefore, appears to have limitations as a vehicle for radioimmunotherapy in patients with breast cancer.
authors.affiliation: Departments of Surgery, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. m.koppe@chir.umcn.nl
authors.forename: Manuel
authors.initials: M
authors.lastname: Koppe
authors.forename: Frank van
authors.initials: Fv
authors.lastname: Schaijk
authors.forename: Jan
authors.initials: J
authors.lastname: Roos
authors.forename: Paul van
authors.initials: Pv
authors.lastname: Leeuwen
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Heider
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kuthan
authors.forename: Robert
authors.initials: R
authors.lastname: Bleichrodt
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D008875:Middle Aged; D011446:Prospective Studies; D016719:Radioimmunodetection; D011868:Radioisotopes; D012211:Rhenium; D012449:Safety
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C112697:CD44v6 antigen; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D011868:Radioisotopes; C479239:monoclonal antibody BIWA 4; D012211:Rhenium