Accumulation of 3-aminopropylphosphonate in the ex vivo brain observed by phosphorus-31 nuclear magnetic resonance

David Shaul; Benjamin Grieb; Naama Lev-Cohain; Jacob Sosna; J. Moshe Gomori; Rachel Katz-Brull

doi:10.1002/nbm.4721

Accumulation of 3-aminopropylphosphonate in the ex vivo brain observed by phosphorus-31 nuclear magnetic resonance

David Shaul, Benjamin Grieb, Naama Lev-Cohain, Jacob Sosna, J. Moshe Gomori, Rachel Katz-Brull^*

^*Corresponding author for this work

Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

3-aminopropylphosphonate (3-APP) is known for its use as an exogenous indicator of extracellular volume and pH in phosphorus-31 nuclear magnetic resonance (³¹P NMR) studies. We used 3-APP for estimating the extracellular volume in NMR studies of several ex vivo preparations including retrograde perfused mouse heart (n = 4), mouse liver slices (n = 2), xenograft breast cancer tumors (n = 7, MCF7), and rat brain slices (n = 4). In the former three preparations, the 3-APP signal was stable in lineshape and intensity for hours and the chemical shift of the signal in the presence of the biological sample was the same as in the perfusion medium without the biological sample. However, in studies of brain slices, the 3-APP signal appeared split into two, with an upfield component (0.7 ± 0.1 ppm to the left) increasing with time and showing a wider linewidth (66.7 ± 12.6 vs. 39.1 ± 7.6 Hz, the latter is of the perfusion medium signal). This finding suggests that 3-APP inadvertently accumulated in brain slices, most likely as a membrane bound form. This observation limits the use of 3-APP as an inert biochemical indicator in brain preparations and should be taken into account when using 3-APP in vivo.

Original language	American English
Article number	e4721
Journal	NMR in Biomedicine
Volume	35
Issue number	8
DOIs	https://doi.org/10.1002/nbm.4721
State	Published - 28 Feb 2022

Bibliographical note

Funding Information:
Israel Science Foundation; Grant Agreement Number: 1379/18. Funding information

Funding Information:
The authors wish to thank Drs. Talia Harris, Atara Nardi‐Schrieber, Gal Sapir, Yael Adler‐Levi, Ayelet Gamliel, and Sivaranjan Uppala, and Mr. Assad Azar for assistance with data collection in the initial phase of this project. This study was funded by the Israel Science Foundation under grant agreement no. 1379/18, by the European Commission (Grant/Award Number: 858149 – AlternativesToGd), and the Jabotinsky Scholarship of the Israeli Ministry of Science and Technology for Applied and Engineering Sciences for Direct PhD Students (No. 3‐15892 for DS).

Publisher Copyright:
© 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

Keywords

3-APA 3-aminopropanephosphinic acid
3-APP 3-aminopropylphosphonate
31P phosphorous NMR spectroscopy
ATP adenosine triphosphate
brain

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10.1002/nbm.4721

Cite this

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title = "Accumulation of 3-aminopropylphosphonate in the ex vivo brain observed by phosphorus-31 nuclear magnetic resonance",

abstract = "3-aminopropylphosphonate (3-APP) is known for its use as an exogenous indicator of extracellular volume and pH in phosphorus-31 nuclear magnetic resonance (31P NMR) studies. We used 3-APP for estimating the extracellular volume in NMR studies of several ex vivo preparations including retrograde perfused mouse heart (n = 4), mouse liver slices (n = 2), xenograft breast cancer tumors (n = 7, MCF7), and rat brain slices (n = 4). In the former three preparations, the 3-APP signal was stable in lineshape and intensity for hours and the chemical shift of the signal in the presence of the biological sample was the same as in the perfusion medium without the biological sample. However, in studies of brain slices, the 3-APP signal appeared split into two, with an upfield component (0.7 ± 0.1 ppm to the left) increasing with time and showing a wider linewidth (66.7 ± 12.6 vs. 39.1 ± 7.6 Hz, the latter is of the perfusion medium signal). This finding suggests that 3-APP inadvertently accumulated in brain slices, most likely as a membrane bound form. This observation limits the use of 3-APP as an inert biochemical indicator in brain preparations and should be taken into account when using 3-APP in vivo.",

keywords = "3-APA 3-aminopropanephosphinic acid, 3-APP 3-aminopropylphosphonate, 31P phosphorous NMR spectroscopy, ATP adenosine triphosphate, brain",

author = "David Shaul and Benjamin Grieb and Naama Lev-Cohain and Jacob Sosna and Gomori, {J. Moshe} and Rachel Katz-Brull",

note = "Funding Information: Israel Science Foundation; Grant Agreement Number: 1379/18. Funding information Funding Information: The authors wish to thank Drs. Talia Harris, Atara Nardi‐Schrieber, Gal Sapir, Yael Adler‐Levi, Ayelet Gamliel, and Sivaranjan Uppala, and Mr. Assad Azar for assistance with data collection in the initial phase of this project. This study was funded by the Israel Science Foundation under grant agreement no. 1379/18, by the European Commission (Grant/Award Number: 858149 – AlternativesToGd), and the Jabotinsky Scholarship of the Israeli Ministry of Science and Technology for Applied and Engineering Sciences for Direct PhD Students (No. 3‐15892 for DS). Publisher Copyright: {\textcopyright} 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.",

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T1 - Accumulation of 3-aminopropylphosphonate in the ex vivo brain observed by phosphorus-31 nuclear magnetic resonance

AU - Shaul, David

AU - Grieb, Benjamin

AU - Lev-Cohain, Naama

AU - Sosna, Jacob

AU - Gomori, J. Moshe

AU - Katz-Brull, Rachel

N1 - Funding Information: Israel Science Foundation; Grant Agreement Number: 1379/18. Funding information Funding Information: The authors wish to thank Drs. Talia Harris, Atara Nardi‐Schrieber, Gal Sapir, Yael Adler‐Levi, Ayelet Gamliel, and Sivaranjan Uppala, and Mr. Assad Azar for assistance with data collection in the initial phase of this project. This study was funded by the Israel Science Foundation under grant agreement no. 1379/18, by the European Commission (Grant/Award Number: 858149 – AlternativesToGd), and the Jabotinsky Scholarship of the Israeli Ministry of Science and Technology for Applied and Engineering Sciences for Direct PhD Students (No. 3‐15892 for DS). Publisher Copyright: © 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

PY - 2022/2/28

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N2 - 3-aminopropylphosphonate (3-APP) is known for its use as an exogenous indicator of extracellular volume and pH in phosphorus-31 nuclear magnetic resonance (31P NMR) studies. We used 3-APP for estimating the extracellular volume in NMR studies of several ex vivo preparations including retrograde perfused mouse heart (n = 4), mouse liver slices (n = 2), xenograft breast cancer tumors (n = 7, MCF7), and rat brain slices (n = 4). In the former three preparations, the 3-APP signal was stable in lineshape and intensity for hours and the chemical shift of the signal in the presence of the biological sample was the same as in the perfusion medium without the biological sample. However, in studies of brain slices, the 3-APP signal appeared split into two, with an upfield component (0.7 ± 0.1 ppm to the left) increasing with time and showing a wider linewidth (66.7 ± 12.6 vs. 39.1 ± 7.6 Hz, the latter is of the perfusion medium signal). This finding suggests that 3-APP inadvertently accumulated in brain slices, most likely as a membrane bound form. This observation limits the use of 3-APP as an inert biochemical indicator in brain preparations and should be taken into account when using 3-APP in vivo.

AB - 3-aminopropylphosphonate (3-APP) is known for its use as an exogenous indicator of extracellular volume and pH in phosphorus-31 nuclear magnetic resonance (31P NMR) studies. We used 3-APP for estimating the extracellular volume in NMR studies of several ex vivo preparations including retrograde perfused mouse heart (n = 4), mouse liver slices (n = 2), xenograft breast cancer tumors (n = 7, MCF7), and rat brain slices (n = 4). In the former three preparations, the 3-APP signal was stable in lineshape and intensity for hours and the chemical shift of the signal in the presence of the biological sample was the same as in the perfusion medium without the biological sample. However, in studies of brain slices, the 3-APP signal appeared split into two, with an upfield component (0.7 ± 0.1 ppm to the left) increasing with time and showing a wider linewidth (66.7 ± 12.6 vs. 39.1 ± 7.6 Hz, the latter is of the perfusion medium signal). This finding suggests that 3-APP inadvertently accumulated in brain slices, most likely as a membrane bound form. This observation limits the use of 3-APP as an inert biochemical indicator in brain preparations and should be taken into account when using 3-APP in vivo.

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KW - 3-APP 3-aminopropylphosphonate

KW - 31P phosphorous NMR spectroscopy

KW - ATP adenosine triphosphate

KW - brain

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DO - 10.1002/nbm.4721

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C2 - 35229366

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SN - 0952-3480

VL - 35

JO - NMR in Biomedicine

JF - NMR in Biomedicine

IS - 8

M1 - e4721

ER -

Accumulation of 3-aminopropylphosphonate in the ex vivo brain observed by phosphorus-31 nuclear magnetic resonance

Abstract

Bibliographical note

Keywords

UN SDGs

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