The Sensitivity of Phosphocholine ¹³C Chemical Shifts to pH

Phosphocholine is a useful magnetic resonance (MR) biomarker for cancer. ¹³C hyperpolarized MR is likely to enhance the detection of this compound by orders of magnitude. The ability to differentiate phosphocholine from its precursor, choline, in live tissues, is unique to MR and depends on the ¹³C chemical shifts. The dependence of phosphocholine ¹³C chemical shifts on pH was investigated. We found that under viable physiological conditions of pH > 7, the chemical shift of phosphocholine ¹³C is stable and the chemical shift distance from the choline ¹³C signals is preserved. Under acidic intracellular conditions of 6.0 < pH < 7, the pH could be sensed by the phosphocholine ¹³C chemical shifts. Crucial and damaging pH changes to values lower than 6.0 could be sensed at very high sensitivity. The highest precision for pH determination is obtained when considering the chemical shift difference between positions 1 and 2 of phosphocholine. The solution composition of human plasma did not affect the response of phosphocholine ¹³C chemical shifts to pH.