Dataset Information

Evaluation of [¹³N]ammonia positron emission tomography as a potential method for quantifying glutamine synthetase activity in the human brain.

ABSTRACT:

Purpose

The conversion of synaptic glutamate to glutamine in astrocytes by glutamine synthetase (GS) is critical to maintaining healthy brain activity and may be disrupted in several brain disorders. As the GS catalysed conversion of glutamate to glutamine requires ammonia, we evaluated whether [¹³N]ammonia positron emission tomography (PET) could reliability quantify GS activity in humans.

Methods

In this test-retest study, eight healthy volunteers each received two dynamic [¹³N]ammonia PET scans on the morning and afternoon of the same day. Each [¹³N]ammonia scan was preceded by a [¹⁵O]water PET scan to account for effects of cerebral blood flow (CBF).

Results

Concentrations of radioactive metabolites in arterial blood were available for both sessions in five of the eight subjects. Our results demonstrated that kinetic modelling was unable to reliably distinguish estimates of the kinetic rate constant k₃ (related to GS activity) from K₁ (related to [¹³N]ammonia brain uptake), and indicated a non-negligible back-flux of [¹³N] to blood (k₂). Model selection favoured a reversible one-tissue compartmental model, and [¹³N]ammonia K₁ correlated reliably (r²?=?0.72-0.92) with [¹⁵O]water CBF.

Conclusion

The [¹³N]ammonia PET method was unable to reliably estimate GS activity in the human brain but may provide an alternative index of CBF.

SUBMITTER: Egerton A

PROVIDER: S-EPMC7714883 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Evaluation of [<sup>13</sup>N]ammonia positron emission tomography as a potential method for quantifying glutamine synthetase activity in the human brain.

Egerton Alice A Dunn Joel T JT Singh Nisha N Yu Zilin Z O'Doherty Jim J Koychev Ivan I Webb Jessica J Claridge Simon S Turkheimer Federico E FE Marsden Paul K PK Hammers Alexander A Gee Antony A

EJNMMI research 20201203 1

<h4>Purpose</h4>The conversion of synaptic glutamate to glutamine in astrocytes by glutamine synthetase (GS) is critical to maintaining healthy brain activity and may be disrupted in several brain disorders. As the GS catalysed conversion of glutamate to glutamine requires ammonia, we evaluated whether [<sup>13</sup>N]ammonia positron emission tomography (PET) could reliability quantify GS activity in humans.<h4>Methods</h4>In this test-retest study, eight healthy volunteers each received two dy ...[more]

PMID: 33270177

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Project description:BackgroundWe previously proposed a technique for quantitative measurement of rest and stress absolute myocardial blood flow (MBF) using a 2-injection single-scan imaging session. Recently, we validated the method in a pig model for the long-lived radiotracer 18F-Flurpiridaz with adenosine as a pharmacological stressor. The aim of the present work is to validate our technique for 13NH3.MethodsNine studies were performed in 6 pigs; 5 studies were done in the native state and 4 after infarction of the left anterior descending artery. Each study consisted of 3 dynamic scans: a 2-injection rest-rest single-scan acquisition (scan A), a 2-injection rest/stress single-scan acquisition (scan B), and a conventional 1-injection stress acquisition (scan C). Variable doses of adenosine combined with dobutamine were administered to induce a wide range of MBF. The 2-injection single-scan measurements were fitted with our nonstationary kinetic model (MGH2). In 4 studies, 13NH3 injections were paired with microsphere injections. MBF estimates obtained with our method were compared with those obtained with the standard method and with microspheres. We used a model-based method to generate separate rest and stress perfusion images.ResultsIn the absence of stress (scan A), the MBF values estimated by MGH2 were nearly the same for the 2-radiotracer injections (mean difference: 0.067±0.070 mL·min-1·cc-1, limits of agreement: [-0.070 to 0.204] mL·min-1·cc-1), showing good repeatability. Bland-Altman analyses demonstrated very good agreement with the conventional method for both rest (mean difference: -0.034±0.035 mL·min-1·cc-1, limits of agreement: [-0.103 to 0.035] mL·min-1·cc-1) and stress (mean difference: 0.057±0.361 mL·min-1·cc-1, limits of agreement: [-0.651 to 0.765] mL·min-1·cc-1) MBF measurements. Positron emission tomography and microsphere MBF measurements correlated closely. Very good quality perfusion images were obtained.ConclusionsThis study provides in vivo validation of our single-scan rest-stress method for 13NH3 measurements. The 13NH3 rest/stress myocardial perfusion imaging procedure can be compressed into a single positron emission tomography scan session lasting less than 15 minutes.

Dataset Information

Evaluation of [¹³N]ammonia positron emission tomography as a potential method for quantifying glutamine synthetase activity in the human brain.

Purpose

Methods

Results

Conclusion

Publications

Evaluation of [<sup>13</sup>N]ammonia positron emission tomography as a potential method for quantifying glutamine synthetase activity in the human brain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Evaluation of [13N]ammonia positron emission tomography as a potential method for quantifying glutamine synthetase activity in the human brain.

Purpose

Methods

Results

Conclusion

Publications

Evaluation of [<sup>13</sup>N]ammonia positron emission tomography as a potential method for quantifying glutamine synthetase activity in the human brain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Evaluation of [¹³N]ammonia positron emission tomography as a potential method for quantifying glutamine synthetase activity in the human brain.