[A commentary: New carbonic anhydrase IX-targeted probes for imaging hypoxic tumors]

In 2023, the journals "Bioconjugate Chemistry" and "Sensors and Actuators B: Chemical" published two papers describing new biosensors for imaging hypoxic regions in tumors. Cao et al. combined acetazolamide (AZA) to target carbonic anhydrase IX (CA IX) with two tyrosine-derived Mn(II)-ethylenediaminetetraacetic acid chelates (TyEDTA) on a rigid triazine (TA) scaffold. The aim of this synthesis was to create a Mn(II)-based magnetic resonance imaging probe named AZA-TA-Mn. In a murine hypoxia model of esophageal squamous cell carcinoma, AZA-TA-Mn, at a low dose of 0.05mmol/kg, produced selective contrast enhancement over non-specific Gd-diethylenetriaminepentaacetic acid (0.1mmol/kg). A competition study involving the co-injection of free AZA and a Mn(II)-based magnetic resonance imaging probe confirmed the in vivo tumor selectivity of AZA-TA-Mn. Immunofluorescence staining of tissue sections confirmed the positive correlation between tumor accumulation of AZA-TA-Mn and overexpression of AC IX. Using CA IX as a biomarker of hypoxia, Cao et al. have thus illustrated a practical strategy for the development of novel imaging probes for specific regions of hypoxia in a tumor of interest.