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Positron Emission Tomography Imaging of Lesions pH Using 11 C-Labeled Bicarbonate.
Cancer Biotherapy & Radiopharmaceuticals 2018 September
OBJECTIVES: 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 11 C-labeled bicarbonate (H11 CO3 - ) buffer and positron emission tomography (PET).
METHODS: H11 CO3 - was produced by on-column NaOH adsorption. Biodistribution of H11 CO3 - in normal mice was determined. In addition, uptake studies and inhibition experiments of H11 CO3 - 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.
RESULTS: PET imaging demonstrated the high uptake of H11 CO3 - 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 H11 CO3 - in mice model tissues had no change. Similarly, administration with ammonium chloride (NH4 Cl) decreased the pH, whereas the unchanged uptake of H11 CO3 - in mice model tissues was also found. However, after administration of acetazolamide, the low uptake of H11 CO3 - in mice model tissues was observed.
CONCLUSIONS: H11 CO3 - solution is an endogenous bicarbonate buffer tracer that can be injected into patients without toxicity. H11 CO3 - PET can be used clinically to image pathological processes that are associated with acid-base imbalance, such as cancer and inflammation.
METHODS: H11 CO3 - was produced by on-column NaOH adsorption. Biodistribution of H11 CO3 - in normal mice was determined. In addition, uptake studies and inhibition experiments of H11 CO3 - 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.
RESULTS: PET imaging demonstrated the high uptake of H11 CO3 - 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 H11 CO3 - in mice model tissues had no change. Similarly, administration with ammonium chloride (NH4 Cl) decreased the pH, whereas the unchanged uptake of H11 CO3 - in mice model tissues was also found. However, after administration of acetazolamide, the low uptake of H11 CO3 - in mice model tissues was observed.
CONCLUSIONS: H11 CO3 - solution is an endogenous bicarbonate buffer tracer that can be injected into patients without toxicity. H11 CO3 - PET can be used clinically to image pathological processes that are associated with acid-base imbalance, such as cancer and inflammation.
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