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CGMP-Compatible preparative scale synthesis of near-infrared fluorophores.

ABSTRACT: 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.

SUBMITTER: Hyun H

PROVIDER: S-EPMC3448123 | biostudies-literature | 2012 Nov-Dec

REPOSITORIES: biostudies-literature

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cGMP-Compatible preparative scale synthesis of near-infrared fluorophores.

Hyun Hoon H Bordo Mark W MW Nasr Khaled K Feith Dina D Lee Jeong Heon JH Kim Soon Hee SH Ashitate Yoshitomo Y Moffitt Lorissa A LA Rosenberg Mireille M Henary Maged M Choi Hak Soo HS Frangioni John V JV

Contrast media & molecular imaging 20121101 6

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 detect ...[more]

PMID: 22991318

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