Exploratory Clinical Investigation of (4<i>S</i>)-4-(3-<sup>18</sup>F-Fluoropropyl)-l-Glutamate PET of Inflammatory and Infectious Lesions

Chae, Su Young; Choi, Chang‐Min; Shim, Tae Sun; Park, Yangsoon; Park, Chan-Sik; Lee, Hyo Sang; Lee, Sang Ju; Oh, Seung Jun; Kim, Seog-Young; Baek, Sora; Koglin, Norman; Stephens, Andrew; Dinkelborg, Ludger; Moon, Dae Hyuk

doi:10.2967/jnumed.115.164020

Cited by 24 publications

(13 citation statements)

References 14 publications

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“… 100 Another clinical study used PET with [ 18 F]FSPG to detect inflammatory lesions provoked by the activation of macrophages in diseases such as sarcoidosis. 101 Several studies support these findings showing that the expression of system xc − is particularly abundant in microglia, macrophages and other immune cells. 102 , 103 In fact, the release of glutamate from both resting and activated microglia by system xc − can induce a regional increase in glutamate levels that leads to excitotoxic oligodendrocyte death contributing to the pathogenesis of white matter disorders.…”

Section: Glutamate Transportersmentioning

confidence: 83%

Inflammation in stroke: the role of cholinergic, purinergic and glutamatergic signaling

Martín

Domercq

Matute

2018

Ther Adv Neurol Disord

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The inflammatory response is a major factor in stroke pathophysiology and contributes to secondary neuronal damage in both acute and chronic stages of the ischemic injury. Recent work in experimental cerebral ischemia has demonstrated the involvement of neurotransmitter signaling in the modulation of neuroinflammation. The present review discusses recent findings on the therapeutic potential and diagnostic perspectives of cholinergic, purinergic and glutamatergic receptors and transporters in experimental stroke. It provides evidence of the role of neurotransmission signaling as a promising inflammatory biomarker in stroke. Finally, recent molecular imaging studies using positron emission tomography of cholinergic receptors and glutamatergic transporters are outlined along with their potential as novel anti-inflammatory therapy to reduce the outcome of cerebral ischemia.

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Section: Glutamate Transportersmentioning

confidence: 83%

Inflammation in stroke: the role of cholinergic, purinergic and glutamatergic signaling

Martín

Domercq

Matute

2018

Ther Adv Neurol Disord

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“…Substantial work on macrophage imaging has been done in the field of inflammation and atherosclerosis. Amongst others, SLC18B1 75, iNOS 76, system x c - 77, somatostatin receptor 78, the chemokine receptor type (CXCR4) 79, and cysteine cathepsins 80, 81 have been successfully explored for macrophage imaging (including optical imaging) but either lack suitable PET tracers or await validation for cancer-associated macrophages. An extensive list of established radiotracers in the preclinical and clinical setting with focus on inflammatory diseases is available in the review of Jiemy and colleagues 19.…”

Section: Macrophage Targeting Radiopharmaceuticalsmentioning

confidence: 99%

The yin and yang of imaging tumor associated macrophages with PET and MRI

Mukherjee¹,

Sonanini²,

Maurer³

et al. 2019

Theranostics

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Tumor associated macrophages (TAM) are key players in the cancer microenvironment. Molecular imaging modalities such as MRI and PET can be used to track and monitor TAM dynamics in tumors non-invasively, based on specific uptake and quantification of MRI-detectable nanoparticles or PET-detectable radiotracers. Particular molecular signatures can be leveraged to target anti-inflammatory TAM, which support tumor growth, and pro-inflammatory TAM, which suppress tumor growth. In addition, TAM-directed imaging probes can be designed to include immune modulating properties, thereby leading to combined diagnostic and therapeutic (theranostic) effects. In this review, we will discuss the complementary role of TAM-directed radiotracers and iron oxide nanoparticles for monitoring cancer immunotherapies with PET and MRI technologies. In addition, we will outline how TAM-directed imaging and therapy is interdependent and can be connected towards improved clinical outcomes

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“…BAY 94-9392 ((4S)-4-(3-[ 18 F]fluoropropyl)-L-glutamate (herein referred to as [ 18 F]FSPG), a fluorine-18-labeled L-glutamate derivative, is taken up by system xc - due to the lack of discrimination between its natural substrate cystine and glutamate for the inward transport 18, 19. [ 18 F]FSPG has shown to be a promising radiotracer to image the amino acid antiporter system xc - in patients with cancer 20, 21 and infectious lesions 22. In this sense, the PET imaging of amino acid transporters with [ 18 F]BAAs (boramino acids) have also showed high tumor-specific accumulation, suggesting that PET imaging of amino acid transporters are promising targeted radiotracers for molecular imaging in oncology and mental disorders 23.…”

Section: Introductionmentioning

confidence: 99%

PET Imaging with [¹⁸F]FSPG Evidences the Role of System xc^- on Brain Inflammation Following Cerebral Ischemia in Rats

Domercq¹,

Szczupak²,

Gejo³

et al. 2016

Theranostics

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In vivo Positron Emission Tomography (PET) imaging of the cystine-glutamate antiporter (system xc-) activity with [18F]FSPG is meant to be an attractive tool for the diagnosis and therapy evaluation of brain diseases. However, the role of system xc- in cerebral ischemia and its involvement in inflammatory reaction has been scarcely explored. In this work, we report the longitudinal investigation of the neuroinflammatory process following transient middle cerebral artery occlusion (MCAO) in rats using PET with [18F]FSPG and the translocator protein (TSPO) ligand [18F]DPA-714. In the ischemic territory, [18F]FSPG showed a progressive binding increase that peaked at days 3 to 7 and was followed by a progressive decrease from days 14 to 28 after reperfusion. In contrast, [18F]DPA-714 evidenced maximum binding uptake values over day 7 after reperfusion. Ex vivo immnunohistochemistry confirmed the up-regulation of system xc- in microglial cells and marginally in astrocytes. Inhibition of system xc- with sulfasalazine and S-4-CPG resulted in increased arginase (anti-inflammatory M2 marker) expression at day 7 after ischemia, together with a decrease in TSPO and microglial M1 proinflammatory markers (CCL2, TNF and iNOS) expression. Taken together, these results suggest that system xc- plays a key role in the inflammatory reaction underlying experimental stroke.

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Exploratory Clinical Investigation of (4S)-4-(3-¹⁸F-Fluoropropyl)-l-Glutamate PET of Inflammatory and Infectious Lesions

Cited by 24 publications

References 14 publications

Inflammation in stroke: the role of cholinergic, purinergic and glutamatergic signaling

Inflammation in stroke: the role of cholinergic, purinergic and glutamatergic signaling

The yin and yang of imaging tumor associated macrophages with PET and MRI

PET Imaging with [¹⁸F]FSPG Evidences the Role of System xc^- on Brain Inflammation Following Cerebral Ischemia in Rats

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Exploratory Clinical Investigation of (4S)-4-(3-18F-Fluoropropyl)-l-Glutamate PET of Inflammatory and Infectious Lesions

Cited by 24 publications

References 14 publications

Inflammation in stroke: the role of cholinergic, purinergic and glutamatergic signaling

Inflammation in stroke: the role of cholinergic, purinergic and glutamatergic signaling

The yin and yang of imaging tumor associated macrophages with PET and MRI

PET Imaging with [18F]FSPG Evidences the Role of System xc- on Brain Inflammation Following Cerebral Ischemia in Rats

Contact Info

Product

Resources

About

Exploratory Clinical Investigation of (4S)-4-(3-¹⁸F-Fluoropropyl)-l-Glutamate PET of Inflammatory and Infectious Lesions

PET Imaging with [¹⁸F]FSPG Evidences the Role of System xc^- on Brain Inflammation Following Cerebral Ischemia in Rats