Safety, pharmacokinetics, immunogenicity, and biodistribution of (186)Re-labeled humanized monoclonal antibody BIWA 4 (Bivatuzumab) in patients with early-stage breast cancer.

Abstract

UNLABELLED:

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: Manuel Koppe, Frank van Schaijk, Jan Roos, Paul van Leeuwen, Karl-Heinz Heider, Hartmut Kuthan, Robert Bleichrodt
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 19 Issue 6 Pg. 720-9 (Dec 2004) ISSN: 1084-9785 [Print] United States
• PMID: 15665619 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• CD44v6 antigen
• Glycoproteins
• Hyaluronan Receptors
• Radioisotopes
• monoclonal antibody BIWA 4
• Rhenium

Topics

• Adult
• Antibodies, Monoclonal (immunology, pharmacokinetics)
• Antibodies, Monoclonal, Humanized
• Breast Neoplasms (diagnostic imaging, metabolism)
• Carcinoma, Ductal, Breast (diagnostic imaging, metabolism)
• Female
• Glycoproteins (immunology)
• Humans
• Hyaluronan Receptors (immunology)
• Middle Aged
• Prospective Studies
• Radioimmunodetection
• Radioisotopes
• Rhenium
• Safety