Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance.

Dysregulation of pH in solid tumors is a hallmark of cancer. In recent years, the role of altered pH heterogeneity in space, between benign and aggressive tissues, between individual cancer cells, and between subcellular compartments, has been steadily elucidated. Changes in temporal pH-related processes on both fast and slow time scales, including altered kinetics of bicarbonate-CO2 exchange and its effects on pH buffering and gradual, progressive changes driven by changes in metabolism, are further implicated in phenotypic changes observed in cancers. These discoveries have been driven by advances in imaging technologies. This review provides an overview of intra- and extracellular pH alterations in time and space reflected in cancer cells, as well as the available technology to study pH spatiotemporal heterogeneity

Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance

Dysregulation of pH in solid tumors is a hallmark of cancer. In recent years, the role of altered pH heterogeneity in space, between benign and aggressive tissues, between individual cancer cells, and between subcellular compartments, has been steadily elucidated. Changes in temporal pH-related processes on both fast and slow time scales, including altered kinetics of bicarbonate-CO2 exchange and its effects on pH buffering and gradual, progressive changes driven by changes in metabolism, are further implicated in phenotypic changes observed in cancers. These discoveries have been driven by advances in imaging technologies. This review provides an overview of intra- and extracellular pH alterations in time and space reflected in cancer cells, as well as the available technology to study pH spatiotemporal heterogeneity

Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance.

Dysregulation of pH in solid tumors is a hallmark of cancer. In recent years, the role of altered pH heterogeneity in space, between benign and aggressive tissues, between individual cancer cells, and between subcellular compartments, has been steadily elucidated. Changes in temporal pH-related processes on both fast and slow time scales, including altered kinetics of bicarbonate-CO2 exchange and its effects on pH buffering and gradual, progressive changes driven by changes in metabolism, are further implicated in phenotypic changes observed in cancers. These discoveries have been driven by advances in imaging technologies. This review provides an overview of intra- and extracellular pH alterations in time and space reflected in cancer cells, as well as the available technology to study pH spatiotemporal heterogeneity

31P nuclear spin singlet lifetimes in a system with switchable magnetic inequivalence: experiment and simulation: experiment and simulation

31P NMR spectroscopy and the study of nuclear spin singlet relaxation phenomena are of interest in particular due to the importance of phosphorus-containing compounds in physiology. We report the generation and measurement of relaxation of 31P singlet order in a chemically equivalent but magnetically inequivalent case. Nuclear magnetic resonance singlet state lifetimes of 31P pairs have heretofore not been reported. Couplings between 1H and 31P nuclei lead to magnetic inequivalence and serve as a mechanism of singlet state population conversion within this molecule. We show that in this molecule singlet relaxation occurs at a rate significantly faster than spin–lattice relaxation, and that anticorrelated chemical shift anisotropy can account for this observation. Calculations of this mechanism, with the help of molecular dynamics simulations and ab initio calculations, provide excellent agreement with the experimental findings. This study could provide guidance for the study of 31P singlets within other compounds, including biomolecules

Tumor Microenvironment Biosensors for Hyperpolarized Carbon-13 Magnetic Resonance Spectroscopy

Hyperpolarization (HP) of a carbon-13 molecule via dynamic nuclear polarization (DNP) involves polarization at low temperature, followed by a dissolution procedure producing a solution with highly polarized spins at room temperature. This dissolution DNP method significantly increases the signal-to-noise ratio (SNR) of nuclear magnetic resonance (NMR) over 10,000-fold and facilitates the use of magnetic resonance spectroscopy (MRS) to image not only metabolism but also the extracellular microenvironment. The extracellular tumor microenvironment (TME) closely interacts with tumor cells and stimulates their growth and metastasis. Thus, the ability to detect pathological changes in the TME is pivotal for the detection and study of cancers. This review highlights the potential use of MRS to study features of the TME-elevated export of lactate, reduced interstitial pH, imbalanced redox equilibrium, and altered metal homeostasis. The promising outcomes of both in vitro and in vivo assays suggest that DNP-MRS may be a useful technique to study aspects of the TME. With continued improvements, this tool has the potential to study the TME and provide guidance for accurate patient stratification and precise personal therapy. Graphical Abstract