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  4. Hyperpolarized (1-13C)Alaninamide Is a Multifunctional In Vivo Sensor of Aminopeptidase N Activity, pH, and CO2
 
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research article

Hyperpolarized (1-13C)Alaninamide Is a Multifunctional In Vivo Sensor of Aminopeptidase N Activity, pH, and CO2

Radaelli, Alice  
•
Ortiz, Daniel  
•
Michelotti, Alessia
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October 4, 2022
Acs Sensors

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.

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Type
research article
DOI
10.1021/acssensors.2c01203
Web of Science ID

WOS:000870033500001

Author(s)
Radaelli, Alice  
•
Ortiz, Daniel  
•
Michelotti, Alessia
•
Roche, Maxime
•
Hata, Ryunosuke
•
Sando, Shinsuke
•
Bonny, Olivier
•
Gruetter, Rolf  
•
Yoshihara, Hikari A. I.  
Date Issued

2022-10-04

Publisher

AMER CHEMICAL SOC

Published in
Acs Sensors
Subjects

Chemistry, Multidisciplinary

•

Chemistry, Analytical

•

Nanoscience & Nanotechnology

•

Chemistry

•

Science & Technology - Other Topics

•

apn

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dynamic nuclear polarization

•

carbon-13

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magnetic resonance

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kidney

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pco2

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carbamate

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functional imaging

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dynamic nuclear-polarization

•

carbamate formation

•

design

Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LIFMET  
Available on Infoscience
November 7, 2022
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/191978
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