Carbonic Anhydrase IX-Targeted Near-Infrared Dye for
Fluorescence Imaging of Hypoxic Tumors
Sakkarapalayam
M. Mahalingam
Haiyan Chu
Xin Liu
Christopher P. Leamon
Philip S. Low
10.1021/acs.bioconjchem.8b00509.s001
https://acs.figshare.com/articles/journal_contribution/Carbonic_Anhydrase_IX-Targeted_Near-Infrared_Dye_for_Fluorescence_Imaging_of_Hypoxic_Tumors/7112042
Use
of tumor-targeted fluorescence dyes to help surgeons identify
otherwise undetected tumor nodules, decrease the incidence of cancer-positive
margins, and facilitate localization of malignant lymph nodes has
demonstrated considerable promise for improving cancer debulking surgery.
Unfortunately, the repertoire of available tumor-targeted fluorescent
dyes does not permit identification of all cancer types, raising the
need to develop additional tumor-specific fluorescent dyes to ensure
localization of all malignant lesions during cancer surgeries. By
comparing the mRNA levels of the hypoxia-induced plasma membrane protein
carbonic anhydrase IX (CA IX) in 13 major human cancers with the same
mRNA levels in corresponding normal tissues, we document that CA IX
constitutes a nearly universal marker for the design of tumor-targeted
fluorescent dyes. Motivated by this expression profile, we synthesize
two new CA IX-targeted near-infrared (NIR) fluorescent imaging agents
and characterize their physical and biological properties both <i>in vitro</i> and <i>in vivo</i>. We report that conjugation
of either acetazolamide or 6-aminosaccharin (i.e., two CA-IX-specific
ligands) to the NIR fluorescent dye, S0456, via an extended phenolic
spacer creates a brightly fluorescent dye that binds CA IX with high
affinity and allows rapid visualization of hypoxic regions of solid
tumors at depths >1 cm beneath a tissue surface. Taken together,
these
data suggest that a CA IX-targeted NIR dye can constitute a useful
addition to a cocktail of tumor-targeted NIR dyes designed to image
all human cancers.
2018-09-06 00:00:00
tumor-targeted NIR dyes
CA IX-targeted NIR dye
CA IX-targeted near-infrared
mRNA levels
cancer debulking surgery
tumor-targeted fluorescence dyes
Carbonic Anhydrase IX-Targeted Near-Infrared Dye
hypoxia-induced plasma membrane protein carbonic anhydrase