Radioimmunotherapy of A431 xenografted mice with pretargeted B3 antibody-streptavidin and (90)Y-labeled 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)-biotin.

Abstract

We investigated the biodistribution of (88)Y/(111)In-labeled 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)-biotin and therapy with (90)Y-labeled DOTA-biotin in tumor-bearing mice after B3-streptavidin antibody conjugate (B3-SA) pretargeting. B3 antibody, recognizing Lewis(y) antigen, was conjugated to streptavidin (B3-SA). For pretargeting, 400 micro g of the B3-SA was injected i.v. into mice bearing A431 tumor xenografts. After tumor localization of B3-SA, 100 micro g of synthetic clearing agent was injected i.v. to clear the unbound B3-SA from the circulation. Four h later, 1 micro g of radiolabeled DOTA-biotin was injected i.v. Radioimmunotherapy was performed with doses of 9.25 to 37 MBq of (90)Y-labeled DOTA-biotin. As a result, radiolabeled DOTA-biotin cleared rapidly. All of the normal tissues had <2.6% of the injected dose per gram, whereas tumor uptake reached approximately 15% ID/g. The total tumor uptake of radioactivity remained similar for 96 h or longer. In the first study, the median survival of the control group was 8 days, whereas it increased to >163 days in the 37 MBq (90)Y group (P < 0.005). In a second therapy group, 7 of 10 mice receiving 37 MBq of (90)Y and B3-SA were cured, and remained healthy for >180 days after therapy, compared with control groups, with </=29.2 days mean survival time (P < 0.001). Tumor pretargeting with B3-SA and radiolabeled DOTA-biotin has shown favorable, specific, and fast targeting that has resulted in good tumor responses and, thus, serves as a rationale for human studies with the B3-SA pretargeting approach.

• Authors: Zhengsheng Yao, Meili Zhang, Donald B Axworthy, Karen J Wong, Kayhan Garmestani, Luke Park, Chang W Park, Robert W Mallett, Louis J Theodore, Eric K Yau, Thomas A Waldmann, Martin W Brechbiel, Chang H Paik, Ira Pastan, Jorge A Carrasquillo
• Journal: Cancer research (Cancer Res) Vol. 62 Issue 20 Pg. 5755-60 (Oct 15 2002) ISSN: 0008-5472 [Print] United States
• PMID: 12384535 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• DOTA-biotin
• Immunoconjugates
• Indium Radioisotopes
• Organometallic Compounds
• Radiopharmaceuticals
• Biotin
• Streptavidin
• Ytterbium

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• Biotin (analogs & derivatives, pharmacokinetics, pharmacology)
• Carcinoma, Squamous Cell (diagnostic imaging, immunology, metabolism, radiotherapy)
• Drug Synergism
• Female
• Humans
• Immunoconjugates (pharmacology)
• Indium Radioisotopes (therapeutic use)
• Mice
• Mice, Nude
• Organometallic Compounds (pharmacokinetics, pharmacology)
• Radioimmunotherapy (methods)
• Radionuclide Imaging
• Radiopharmaceuticals (pharmacokinetics, pharmacology)
• Streptavidin (pharmacology)
• Tissue Distribution
• Xenograft Model Antitumor Assays
• Ytterbium (therapeutic use)