TY - JOUR
T1 - Imaging of pH in vivo using hyperpolarized 13C-labelled zymonic acid
AU - Düwel, Stephan
AU - Hundshammer, Christian
AU - Gersch, Malte
AU - Feuerecker, Benedikt
AU - Steiger, Katja
AU - Buck, Achim
AU - Walch, Axel
AU - Haase, Axel
AU - Glaser, Steffen J.
AU - Schwaiger, Arkus
AU - Schilling, Franz
N1 - Publisher Copyright:
© The Author(s) 2017.
PY - 2017
Y1 - 2017
N2 - Natural pH regulatory mechanisms can be overruled during several pathologies such as cancer, inflammation and ischaemia, leading to local pH changes in the human body. Here we demonstrate that 13C-labelled zymonic acid (ZA) can be used as hyperpolarized magnetic resonance pH imaging sensor. ZA is synthesized from [1-13C]pyruvic acid and its 13C resonance frequencies shift up to 3.0 p.p.m. per pH unit in the physiological pH range. The long lifetime of the hyperpolarized signal enhancement enables monitoring of pH, independent of concentration, temperature, ionic strength and protein concentration. We show in vivo pH maps within rat kidneys and subcutaneously inoculated tumours derived from a mammary adenocarcinoma cell line and characterize ZA as non-toxic compound predominantly present in the extracellular space. We suggest that ZA represents a reliable and non-invasive extracellular imaging sensor to localize and quantify pH, with the potential to improve understanding, diagnosis and therapy of diseases characterized by aberrant acid-base balance.
AB - Natural pH regulatory mechanisms can be overruled during several pathologies such as cancer, inflammation and ischaemia, leading to local pH changes in the human body. Here we demonstrate that 13C-labelled zymonic acid (ZA) can be used as hyperpolarized magnetic resonance pH imaging sensor. ZA is synthesized from [1-13C]pyruvic acid and its 13C resonance frequencies shift up to 3.0 p.p.m. per pH unit in the physiological pH range. The long lifetime of the hyperpolarized signal enhancement enables monitoring of pH, independent of concentration, temperature, ionic strength and protein concentration. We show in vivo pH maps within rat kidneys and subcutaneously inoculated tumours derived from a mammary adenocarcinoma cell line and characterize ZA as non-toxic compound predominantly present in the extracellular space. We suggest that ZA represents a reliable and non-invasive extracellular imaging sensor to localize and quantify pH, with the potential to improve understanding, diagnosis and therapy of diseases characterized by aberrant acid-base balance.
UR - http://www.scopus.com/inward/record.url?scp=85029694268&partnerID=8YFLogxK
U2 - 10.1038/ncomms15126
DO - 10.1038/ncomms15126
M3 - Article
C2 - 28492229
AN - SCOPUS:85029694268
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
M1 - 15126
ER -