Positron Emission Tomography Imaging of Lesions pH Using ¹¹C-Labeled Bicarbonate

As acid-base imbalance is involved in many pathological processes, the capability to image tissue pH alterations in the clinic could offer new ways to detect disease and respond to treatment. In this study, the authors show that tissue pH can be imaged in vivo with ¹¹C-labeled bicarbonate (H¹¹CO₃^-) buffer and positron emission tomography (PET).

H¹¹CO₃^- was produced by on-column NaOH adsorption. Biodistribution of H¹¹CO₃^- in normal mice was determined. In addition, uptake studies and inhibition experiments of H¹¹CO₃^- in the S180 fibrosarcoma-bearing mice and the inflammatory mice were investigated with PET imaging. The tumor and inflammatory interstitial pH was measured by a needle pH microelectrode.

PET imaging demonstrated the high uptake of H¹¹CO₃^- in mice tumor tissues and inflammatory tissues, which showed that the average tumor or inflammatory interstitial pH was significantly lower than the surrounding tissue. Administration of sodium bicarbonate in the drinking water increased the measured tumor pH, while the uptake of H¹¹CO₃^- in mice model tissues had no change. Similarly, administration with ammonium chloride (NH₄Cl) decreased the pH, whereas the unchanged uptake of H¹¹CO₃^- in mice model tissues was also found. However, after administration of acetazolamide, the low uptake of H¹¹CO₃^- in mice model tissues was observed.

H¹¹CO₃^- solution is an endogenous bicarbonate buffer tracer that can be injected into patients without toxicity. H¹¹CO₃^- PET can be used clinically to image pathological processes that are associated with acid-base imbalance, such as cancer and inflammation.