期刊
ACS SENSORS
卷 7, 期 10, 页码 2987-2994出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssensors.2c01203
关键词
APN; dynamic nuclear polarization; carbon-13; magnetic resonance; kidney; pCO2; carbamate; functional imaging
资金
- NIBIB (NIH) [642773]
- Swiss State Secretariat for Education, Research and Innovation (SERI) within the Marie Curie Initial Training Network EUROPOL project
- Centre d'Imagerie BioMedicale (CIBM) of the UNIL
- UNIGE
- Leenards and Jeantet Foundations
- HUG
- CHUV
- EPFL
- [P41EB013598]
- [15.0164]
This study demonstrates the feasibility of using spin hyperpolarization to perform real-time metabolic imaging of carbon-13-labeled substrates. It shows that hyperpolarized L-(1-13C)alaninamide can serve as a probe to detect the activity of the cell-surface tumor marker aminopeptidase-N. Furthermore, it reveals that the chemical shift of alaninamide is pH-sensitive and can be used to measure the pH levels in different compartments.
Spin hyperpolarization enables real-time metabolic imaging of carbon-13-labeled substrates. While hyperpolarized L- (1-13C)alaninamide is a probe of the cell-surface tumor marker aminopeptidase-N (APN, CD13), its activity in vivo has not been described. Scanning the kidneys of rats infused with hyperpolarized alaninamide shows both conversion to [1-13C]alanine and several additional spectral peaks with distinct temporal dynamics. The (1-13C)alaninamide chemical shift is pH-sensitive, with a pKa of 7.9 at 37 degrees C, and the peaks correspond to at least three different compartments of pH 7.46 +/- 0.02 (1), 7.21 +/- 0.02 (2), and 6.58 +/- 0.05 (3). An additional peak was assigned to the carboxyamino adduct formed by reaction with dissolved CO2. Spectroscopic imaging showed nonuniform distribution, with the low-pH signal more concentrated in the inner medulla. Treatment with the diuretic acetazolamide resulted in significant pH shifts in compartment 1 to 7.38 +/- 0.03 (p = 0.0057) and compartment 3 to 6.80 +/- 0.05 (p = 0.0019). While the pH of compartment 1 correlates with blood pH, the pH of compartment 3 did not correspond to the pH of urine. In vitro experiments show that alaninamide readily enters blood cells and can detect intracellular pH. While carbamate formation depends on pH and pCO2, the carbamate-toalaninamide ratio did not correlate with either arterial blood pH or pCO2, suggesting that it may reflect variations in tissue pH and pCO2. This study demonstrates the feasibility of using hyperpolarized sensors to simultaneously image enzyme activity, pCO2, and pH in vivo.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据