Imaging carbonic anhydrase activity using hyperpolarized 13 C - labeled bicarbonate

Introduction We have shown previously that C-labeled bicarbonate (HCO3 ) can be hyperpolarized using Dynamic Nuclear Polarisation (DNP) and that when this is injected in vivo, the enzyme carbonic anhydrase (CA) rapidly interconverts this with carbon dioxide (CO2) [1]. Furthermore, we have also shown that selective saturation of the CO2 signal in vivo will decrease the H CO3 signal in the presence of the enzyme. The rate at which the HCO3 signal decreases depends on the activity of the enzyme. CA is of biological importance because tumor-associated CAs (e.g. CAIX) have been shown to be strongly induced by hypoxia and controlled by hypoxia-inducible factor-1 (HIF-1) [2]. Therefore imaging CA may directly relate to hypoxia and HIF-1 activation.