cGMP-Compatible preparative scale synthesis of near-infrared fluorophores (pages 516–524)
Hoon Hyun, Mark W. Bordo, Khaled Nasr, Dina Feith, Jeong Heon Lee, Soon Hee Kim, Yoshitomo Ashitate, Lorissa A. Moffitt, Mireille Rosenberg, Maged Henary, Hak Soo Choi and John V. Frangioni
Version of Record online: 18 SEP 2012 | DOI: 10.1002/cmmi.1484
Clinical grade zwitterionic near-infrared (NIR) fluorophore ZW800-1 was prepared for image-guided surgery. We describe cGMP-compatible synthesis of ultrapure ZW800-1 through facile and efficient procedures at the 10-gram scale. ZW800-1 has > 90% yield at the final step and > 99% purity as measured by fluorescence and evaporative light scatter detection. We describe an analytical framework to quantitate impurities, as well as a detailed analysis of counterion identities. The unique in vivo properties of ZW800-1, including rapid renal excretion and low nonspecific background binding were confirmed in large animals approaching the size of humans, thus enabling rapid clinical translation.