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Open Access 01-12-2020 | Positron Emission Tomography | Original research

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

Authors: Alice Egerton, Joel T. Dunn, Nisha Singh, Zilin Yu, Jim O’Doherty, Ivan Koychev, Jessica Webb, Simon Claridge, Federico E. Turkheimer, Paul K. Marsden, Alexander Hammers, Antony Gee

Published in: EJNMMI Research | Issue 1/2020

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.

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Title: Evaluation of [ 13 N]ammonia positron emission tomography as a potential method for quantifying glutamine synthetase activity in the human brain
Authors: Alice Egerton
Joel T. Dunn
Nisha Singh
Zilin Yu
Jim O’Doherty
Ivan Koychev
Jessica Webb
Simon Claridge
Federico E. Turkheimer
Paul K. Marsden
Alexander Hammers
Antony Gee
Publication date: 01-12-2020
Publisher: Springer Berlin Heidelberg
Keyword: Positron Emission Tomography
Published in: EJNMMI Research / Issue 1/2020
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-020-00731-0

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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