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

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, reco...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2002-10, Vol.62 (20), p.5755
Main Authors: Yao, Zhengsheng, Zhang, Meili, Axworthy, Donald B, Wong, Karen J, Garmestani, Kayhan, Park, Luke, Park, Chang W, Mallett, Robert W, Theodore, Louis J, Yau, Eric K, Waldmann, Thomas A, Brechbiel, Martin W, Paik, Chang H, Pastan, Ira, Carrasquillo, Jorge A
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - pharmacology
Biotin - analogs & derivatives
Biotin - pharmacokinetics
Biotin - pharmacology
Carcinoma, Squamous Cell - diagnostic imaging
Carcinoma, Squamous Cell - immunology
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - radiotherapy
Drug Synergism
Female
Humans
Immunoconjugates - pharmacology
Indium Radioisotopes - therapeutic use
Mice
Mice, Nude
Organometallic Compounds - pharmacokinetics
Organometallic Compounds - pharmacology
Radioimmunotherapy - methods
Radionuclide Imaging
Radiopharmaceuticals - pharmacokinetics
Radiopharmaceuticals - pharmacology
Streptavidin - pharmacology
Tissue Distribution
Xenograft Model Antitumor Assays
Ytterbium - therapeutic use
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Summary: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 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
ISSN:0008-5472