Tumor pH and Its Measurement

Abstract

Studies over the last few decades have demonstrated that intracellular pH (pHi) of solid tumors is maintained within a pH range of 7.0-7.2, while the extracellular pH (pHe) is acidic. A low pHe may be an important factor inducing more aggressive cancer phenotypes. Research into causes and consequences of this acid pH of tumors are highly dependent on accurate, precise and reproducible measurements, and these have undergone great changes since in the last decade. This review focuses on most recent advances of in vivo tumor pH measurement by pH-sensitive Positron emission tomography (PET) radiotracers, magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI) and optical imaging.

Ratiometric Imaging of pH Probes

“…More recently, PET imaging using radiolabeled probes has allowed for estimation of pHi; however, these measurements are imprecise because they rely on stable distribution of the probe that cannot be independently determined. Similar MRI-based techniques show low sensitivity (Miesenböck et al, 1998;Zhang, Lin, & Gillies, 2010). However, with the advent of fluorescent pH probes and quantitative confocal microscopy, it is now possible to accurately measure pHi in whole-mount tissues and in situ.…”

Multiplexed imaging for diagnosis and therapy

“…Recent findings of deficient 13 C-lactate production in isocitrate dehydrogenase 1 mutant brain tumours, compared to glioblastomas, for example, provide also opportunities for tumour typing with hyperPET. Besides direct clinical application, the multiplexing of MR using hyperpolarized bicarbonate (H 13 CO3 -) with other techniques evaluating tissue acidity 183 and carbonic anhydrase-IX (CAIX) expression [184][185][186] could improve the understanding of the relationship between pH of tumour tissue and its microenvironment, and could potentially lead to the clinical translation of these agents.…”

MRI-based communication for untethered intelligent medical microrobots

“…Studies illustrate that when a tumor starts to grow, it changes some of its nearby micro-environmental variables such as pH level. The extracellular pH (pHe) of a tumor is usually lower than the one of normal cells [127,128]. Hence, a pH level of less than a predetermined threshold would trigger the communication part of the microrobot, and the direction or the frequency of its electrical current will vary depending on the pH level.…”