Open AccesscGMP‐Compatible preparative scale synthesis of near‐infrared fluorophores
Author(s) -
Hyun Hoon,
Bordo Mark W.,
Nasr Khaled,
Feith Dina,
Lee Jeong Heon,
Kim Soon Hee,
Ashitate Yoshitomo,
Moffitt Lorissa A.,
Rosenberg Mireille,
Henary Maged,
Choi Hak Soo,
Frangioni John V.
Publication year - 2012
Publication title -
contrast media & molecular imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.714
H-Index - 50
eISSN - 1555-4317
pISSN - 1555-4309
DOI - 10.1002/cmmi.1484
Subject(s) - indocyanine green , fluorophore , counterion , fluorescence , chromatography , chemistry , infrared , impurity , yield (engineering) , combinatorial chemistry , materials science , organic chemistry , optics , medicine , surgery , ion , physics , metallurgy
Image‐guided surgery using optical imaging requires the availability of large quantities of clinical‐grade fluorophores. We describe the cGMP‐compatible synthesis of the zwitterionic heptamethine indocyanine near‐infrared fluorophore ZW800‐1 at the 10 g scale (~1000 patient doses) using facile and efficient solvent purification, and without the need for column chromatography. 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 for qualifying impurities, as well as a detailed analysis of counterion identities. Finally, we report the unique in vivo properties of ZW800‐1 in large animals approaching the size of humans, thus laying the foundation for rapid clinical translation of these methods. Copyright © 2012 John Wiley & Sons, Ltd.