Zirconium tetraazamacrocycle complexes display extraordinary stability and provide a new strategy for zirconium-89-based radiopharmaceutical development12. Issue 3 (20th December 2016)

• Record Type: Journal Article
• Authors: Pandya, Darpan N.; Bhatt, Nikunj; Yuan, Hong; Day, Cynthia S.; Ehrmann, Brandie M.; Wright, Marcus; Bierbach, Ulrich; Wadas, Thaddeus J.
• Is Part Of: Chemical science. Volume 8:Issue 3(2017)
• Page Start: 2309
• Page End: 2314
• Publication Date: 2016-12-20
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c6sc04128k
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : 89 Zr–Tetraazamacrocycle complexes display extraordinary stability. Abstract : 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 89 Zr–DOTA is superior to 89 Zr–DFO, the only 89 Zr-complex to be used clinically in 89 Zr-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.