Safety,Pharmacokinetics,Immunogenicity,and Biodistribution of 186 Re-Labeled Humanized Monoclonal Antibody BIWA 4 (Bivatuzumab( in Patients with Early-Stage Breast Cancer

The aim of this prospective study was to evaluate the safety, pharmacokinetics, immunogenicity, and biodistribution of ¹⁸⁶Re-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 ¹⁸⁶Re-BIWA 4 was determined by radioactivity measurements in tumor and normal tissue biopsies obtained during surgery 1 week after administration. Administration of ¹⁸⁶Re-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 ¹⁸⁶Re-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.