评估[N]氨正电子发射断层扫描作为定量人类大脑中谷氨酰胺合成酶活性的潜在方法。

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

作者信息

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

机构信息

Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London, SE5 8AF, UK.

School of Biomedical Engineering and Imaging Sciences, St Thomas' Hospital, King's College London, London, SE1 7EH, UK.

出版信息

EJNMMI Res. 2020 Dec 3;10(1):146. doi: 10.1186/s13550-020-00731-0.

DOI:10.1186/s13550-020-00731-0

PMID:33270177

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7714883/

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 [N]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 [N]ammonia PET scans on the morning and afternoon of the same day. Each [N]ammonia scan was preceded by a [O]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 k (related to GS activity) from K (related to [N]ammonia brain uptake), and indicated a non-negligible back-flux of [N] to blood (k). Model selection favoured a reversible one-tissue compartmental model, and [N]ammonia K correlated reliably (r = 0.72-0.92) with [O]water CBF.

CONCLUSION

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

摘要

目的

谷氨酰胺合成酶（GS）在星形胶质细胞中将突触谷氨酸转化为谷氨酰胺对于维持健康的大脑活动至关重要，并且在几种脑部疾病中可能会受到干扰。由于GS催化的谷氨酸向谷氨酰胺的转化需要氨，我们评估了[氮]氨正电子发射断层扫描（PET）是否能够可靠地量化人类的GS活性。

方法

在这项重测研究中，八名健康志愿者在同一天的上午和下午分别接受了两次动态[氮]氨PET扫描。每次[氮]氨扫描之前都进行了一次[氧]水PET扫描，以考虑脑血流量（CBF）的影响。

结果

八名受试者中有五名在两个时间段都获得了动脉血中放射性代谢物的浓度。我们的结果表明，动力学建模无法可靠地区分动力学速率常数k（与GS活性相关）和K（与[氮]氨脑摄取相关）的估计值，并表明[氮]向血液（k）的反向通量不可忽略。模型选择倾向于可逆的单组织隔室模型，并且[氮]氨K与[氧]水CBF可靠相关（r = 0.72 - 0.92）。