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211At-labeled immunoconjugate via a one-pot three-component double click strategy: practical access to α-emission cancer radiotherapeutics
- Source :
- Chemical Science. 10:1936-1944
- Publication Year :
- 2019
- Publisher :
- Royal Society of Chemistry (RSC), 2019.
-
Abstract
- α-Emission radiotherapeutics has potential to be one of most effective cancer therapeutics. Herein, we report a facile synthesis of an 211At-labeled immunoconjugate for use as an α-emission molecular targeting therapy. We synthesized a tetrazine probe modified with closo-decaborate(2-), a prosthetic group that forms a bioavailable stable complex with 211At. Our one-pot three-component double-click labeling method was used to attach decaborate to trastuzumab (anti-HER2 antibody) using decaborate-tetrazine and TCO-aldehyde probes without reducing the antibody binding affinity. Labeling the decaborate-attached trastuzumab with 211At produced in the cyclotron at the RIKEN Nishina Center, at which highly radioactive 211At can be produced, readily furnished the 211At-labeled trastuzumab with a maximum specific activity of 15 MBq μg−1 and retention of the native binding affinity. Intratumor injection of the 211At-labeled trastuzumab in BALB/c nude mice implanted with HER2-expressing epidermoid cancer cells yielded efficient accumulation at the targeted tumor site as well as effective suppression of tumor growth.
- Subjects :
- biology
010405 organic chemistry
Cancer
General Chemistry
010402 general chemistry
medicine.disease
01 natural sciences
0104 chemical sciences
Immunoconjugate
Tetrazine
chemistry.chemical_compound
chemistry
Trastuzumab
Cancer cell
Cancer research
medicine
biology.protein
Tumor growth
Specific activity
Antibody
skin and connective tissue diseases
medicine.drug
Subjects
Details
- ISSN :
- 20416539 and 20416520
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Chemical Science
- Accession number :
- edsair.doi...........85f861cb0397c5d796a77bba07c7da25