Journal
CHEMICAL SCIENCE
Volume 8, Issue 3, Pages 2309-2314Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c6sc04128k
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Funding
- Wake Forest University Health Sciences
- Wake Forest Innovations
- Wake Forest Baptist Medical Center
- North Carolina Biotechnology Center [2016-BIG-6524]
- Comprehensive Cancer Center grant [P30CA016086]
- National Science Foundation [CHE-0234489]
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We report our initial investigations into the use of tetraazamacrocycles as zirconium-89 chelators. We describe the synthesis and complete characterization of several Zr tetraazamacrocycle complexes, and definitively describe the first crystal structure of zirconium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Zr-DOTA) using single crystal X-ray diffraction analysis. After evaluating several radioactive analogs, we found that Zr-89-DOTA is superior to Zr-89-DFO, the only Zr-89-complex to be used clinically in Zr-89-radiopharmaceutical applications. Finally, we provide a rationale for the unanticipated and extraordinary stability of these complexes in vitro and in vivo. These results may inform the development of safer and more robust immuno-PET agents for precision medicine applications.
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