Design and synthesis of highly fluorescent cobalamin analogs for cancer imaging

ORGN 798

Manfai Lee, manfai@chem.utah.edu and Charles B. Grissom, grissomc@chem.utah.edu. Department of Chemistry, University of Utah, 315 S. 1400 E, Salt Lake City, UT 84112-0850
Fluorescent cobalamin conjugates are useful as cancer diagnostic and tumor imaging agents. The increased transport and sequestration of cobalamin by cancer cells enables the intraoperative imaging of tumors, as well as visual lymphatic mapping. Cobalamin analogues have been synthesized in which the spatial interaction of the corrin ring and the pendant fluorophore is minimized, thereby decreasing dipolar quenching of the fluorophore. Cobalamin conjugates that incorporate fluorescein and rhodamine fluorophores have been synthesized and characterized. Derivatization of the cobalamin ribose 5'-OH moiety does not significantly affect its uptake by transcobalamin-dependent receptors on the surface of mammalian cells.