PET Imaging of the P2X7 Ion Channel with a Novel Tracer [18F]JNJ-64413739 in a Rat Model of Neuroinflammation.

Autor:	Berdyyeva, Tamara, Xia, Chunfang, Taylor, Natalie, He, Yingbo, Chen, Gang, Huang, Chaofeng, Zhang, Wei, Kolb, Hartmuth, Letavic, Michael, Bhattacharya, Anindya, Szardenings, Anna Katrin
Předmět:	RADIOACTIVE tracers POSITRON emission tomography LIPOPOLYSACCHARIDES BRAINWASHING ION channels POLYMERASE chain reaction ADENOSINE triphosphate RATS BRAIN BIOLOGICAL models PILOT projects PYRIDINE RESEARCH ANIMAL experimentation HETEROCYCLIC compounds RESEARCH methodology CELL receptors EVALUATION research NEUROINFLAMMATION COMPARATIVE studies RADIOPHARMACEUTICALS PEPTIDES EMISSION-computed tomography
Zdroj:	Molecular Imaging & Biology; Oct2019, Vol. 21 Issue 5, p871-878, 8p
Abstrakt:	Purpose: The P2X7 receptor, an adenosine triphosphate (ATP)-gated purinoreceptor, has emerged as one of the key players in neuroinflammatory processes. Therefore, developing a positron emission tomography (PET) tracer for imaging of P2X7 receptors in vivo presents a promising approach to diagnose, monitor, and study neuroinflammation in a variety of brain disorders. To fulfill the goal of developing a P2X7 PET ligand as a biomarker of neuroinflammation, [18F]JNJ-64413739 has been recently disclosed.Procedures: We evaluated [18F]JNJ-64413739 in a rat model of neuroinflammation induced by an intracerebral injection of lipopolysaccharide (LPS). In vivo brain uptake was determined by PET imaging. Upregulation of neuroinflammatory biomarkers was determined by quantitative polymerase chain reaction (qPCR). Distribution of the tracer in the brain was determined by ex vivo autoradiography (ARG). The specificity of [18F]JNJ-64413739 was confirmed by performing blocking experiments with the P2X7 antagonist JNJ-54175446.Results: Brain regions of rats injected with LPS had a significantly increased uptake (34 % ± 3 % s.e.m., p = 0.036, t test, standardized uptake value measured over the entire scanning period) of [18F]JNJ-64413739 relative to the corresponding brain regions of control animals injected with phosphate-buffered saline (PBS). The uptake in the contralateral regions and cerebellum was not significantly different between the groups of animals. The increase in uptake of [18F]JNJ-64413739 at the LPS-injected site observed by PET imaging was concordant with ex vivo ARG, upregulation of neuroinflammatory biomarkers, and elevated P2X7 expression levels.Conclusions: While further work is needed to study [18F]JNJ-64413739 in other types of neuroinflammation, the current results favorably characterize [18F]JNJ-64413739 as a potential PET tracer of central neuroinflammation. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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