Carbonic Anhydrase IX-Targeted Near-Infrared Dye for Fluorescence Imaging of Hypoxic Tumors

Area of Science:

• Oncology
• Biomedical Imaging
• Organic Chemistry

Background:

• Tumor-targeted fluorescence dyes enhance cancer surgery by identifying nodules and improving margin status.
• Current dyes are insufficient for all cancer types, necessitating new agents for comprehensive tumor localization.
• Carbonic anhydrase IX (CA IX) is a hypoxia-induced protein overexpressed across many human cancers.

Purpose of the Study:

• To identify a universal tumor marker for developing novel fluorescent dyes.
• To synthesize and characterize new CA IX-targeted near-infrared (NIR) fluorescent imaging agents.
• To evaluate the efficacy of these agents for visualizing deep tumor tissues in vivo.

Main Methods:

• Compared CA IX mRNA levels in 13 human cancers versus normal tissues.
• Synthesized two NIR fluorescent dyes by conjugating CA IX-specific ligands (acetazolamide or 6-aminosaccharin) to the S0456 dye via a phenolic spacer.
• Characterized the dyes' physical and biological properties in vitro and in vivo, assessing binding affinity and tissue penetration.

Main Results:

• CA IX was identified as a highly prevalent marker across 13 major human cancers.
• The synthesized CA IX-targeted NIR dyes exhibited bright fluorescence and high binding affinity for CA IX.
• These agents successfully visualized hypoxic tumor regions at depths greater than 1 cm beneath the tissue surface.

Conclusions:

• CA IX is a promising universal target for developing tumor-specific fluorescent dyes.
• The novel CA IX-targeted NIR dyes are effective for deep-tissue tumor visualization in preclinical models.
• These agents could complement existing dyes in a cocktail for comprehensive imaging of all human cancers during surgery.