Imaging of carrageenan-induced local inflammation and adjuvant-induced systemic arthritis with [11C]PBR28 PET

Shao, Xia; Wang, Xueding; English, Sean; Desmond, Timothy J.; Sherman, Phillip; Quesada, Carole; Piert, Morand

doi:10.1016/j.nucmedbio.2013.06.008

Cited by 21 publications

(24 citation statements)

References 43 publications

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“…Moreover, Folkersma et al [30] suggest that PET data from any disease model where blood brain barrier (BBB) damage is present cannot be quantified using a reference tissue approach with anatomical reference input. Many studies have resorted to semi-quantitation, including use of standardised uptake values (SUVs) [31] and lesion-to-background ratios [32]. There is no consensus over tracer or model-specific quantification approaches, but previous studies involving a unilateral effect have used the cerebellum [33] or a contralateral reference region [22, 23] together with the simplified reference tissue model (SRTM) or MRTM (multilinear reference tissue model) [34].…”

Section: Introductionmentioning

confidence: 99%

Comparative Evaluation of Three TSPO PET Radiotracers in a LPS-Induced Model of Mild Neuroinflammation in Rats

Sridharan

Lepelletier

Trigg³

et al. 2016

Mol Imaging Biol

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PurposeOver the past 20 years, neuroinflammation (NI) has increasingly been recognised as having an important role in many neurodegenerative diseases, including Alzheimer’s disease. As such, being able to image NI non-invasively in patients is critical to monitor pathological processes and potential therapies targeting neuroinflammation. The translocator protein (TSPO) has proven a reliable NI biomarker for positron emission tomography (PET) imaging. However, if TSPO imaging in acute conditions such as stroke provides strong and reliable signals, TSPO imaging in neurodegenerative diseases has proven more challenging. Here, we report results comparing the recently developed TSPO tracers [18F]GE-180 and [18F]DPA-714 with (R)-[11C]PK11195 in a rodent model of subtle focal inflammation.ProceduresAdult male Wistar rats were stereotactically injected with 1 μg lipopolysaccharide in the right striatum. Three days later, animals underwent a 60-min PET scan with (R)-[11C]PK11195 and [18F]GE-180 (n = 6) or [18F]DPA-714 (n = 6). Ten animals were scanned with either [18F]GE-180 (n = 5) or [18F]DPA-714 (n = 5) only. Kinetic analysis of PET data was performed using the simplified reference tissue model (SRTM) with a contralateral reference region or a novel data-driven input to estimate binding potential BPND. Autoradiography and immunohistochemistry were performed to confirm in vivo results.ResultsAt 40–60 min post-injection, [18F]GE-180 dual-scanned animals showed a significantly increased core/contralateral uptake ratio vs. the same animals scanned with (R)-[11C]PK11195 (3.41 ± 1.09 vs. 2.43 ± 0.39, p = 0.03); [18]DPA-714 did not (2.80 ± 0.69 vs. 2.26 ± 0.41). Kinetic modelling with a contralateral reference region identified significantly higher binding potential (BPND) in the core of the LPS injection site with [18F]GE-180 but not with [18F]DPA-714 vs. (R)-[11C]PK11195. A cerebellar reference region and novel data-driven input to the SRTM were unable to distinguish differences in tracer BPND.ConclusionsSecond-generation TSPO-PET tracers are able to accurately detect mild-level NI. In this model, [18F]GE-180 shows a higher core/contralateral ratio and BPND when compared to (R)-[11C]PK11195, while [18F]DPA-714 did not.Electronic supplementary materialThe online version of this article (doi:10.1007/s11307-016-0984-3) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Comparative Evaluation of Three TSPO PET Radiotracers in a LPS-Induced Model of Mild Neuroinflammation in Rats

Sridharan

Lepelletier

Trigg³

et al. 2016

Mol Imaging Biol

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“…This protein can be viewed as a marker for CNS immune activation, because changes in TSPO levels have been shown to reflect changes in glial cell activity. 19,20 TSPO expression is typically elevated in several acute and chronic CNS disorders involving the immune system [21][22][23][24][25] as well as in animal models of acute inflammation 26 or stroke. 19 With regard to periphery-to-brain interactions, lipopolysaccharide (LPS)-induced acute systemic inflammation is followed by a rapid and transient activation of the brain immune system, as demonstrated using the TSPO radioligand [ 11 C]PBR28 in nonhuman primates 27 and humans.…”

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confidence: 99%

The immune response of the human brain to abdominal surgery

Forsberg

Červenka

Fagerlund

et al. 2017

Annals of Neurology

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Objective: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short-and longterm impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. Methods: Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [ 11 C]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed. Results: Patients showed a global downregulation of gray matter [ 11 C]PBR28 binding of 26 6 26% (mean 6 standard deviation) at 3 to 4 days postoperatively compared to baseline (p 5 0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-a in blood displayed a reduction (41 6 39%) on the 3rd to 4th postoperative day, corresponding to changes in [ 11 C]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [ 11 C]PBR28 binding (p 5 0.027). Interpretation: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function. ANN NEUROL 2017;81:572-582 A growing body of evidence suggests that surgical trauma launches a systemic inflammatory response that ultimately reaches and activates the intrinsic immune system of the brain. [1][2][3][4] Triggered by surgery-induced damage-associated molecular patterns (DAMPs), an array of proinflammatory mediators and activated blood-borne immune cells orchestrate a rapid spread of this systemic response to the central nervous system (CNS), with inflammatory markers detectable in human cerebrospinal fluid (CSF) within 12 hours. [4][5][6][7] In surgical rodent models, this periphery-to-brain pathway seems critically dependent on NF-jB and proinflammatory cytokine signaling (eg, tumor necrosis factor-a [TNF-a]) associated with a shortlasting disruption of blood-brain barrier integrity, 2,3,8 migration of peripheral macrophages into the CNS, and subsequent hippocampal neuronal dysfunction and cognitive impairment. 8 In addition to an acute and transient response, often referred to as a syndrome of sickness behavior including fatigue, anorexia, and fever, surgery-induced immune activation may be associated with prolonged impairments in learning,...

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“…All TSPO-specific radiotracers bind to TSPO-rich cardiac, lung and liver and are typically restricted to interrogation of tissues with low endogenous TSPO expression, such as the brain[32, 33]. However a recent report described the use of [ 18 F]DPA-714 in rheumatoid arthritis (RA), where minimal background uptake would be expected [34], as well as the use of [ 18 F]PBR28 to image another rodent model of RA[35]. To date, only one TSPO-targeted radiotracer has been used clinically to delineate atherosclerotic plaque, namely, [ 11 C]( R )-PK11195[22].…”

Section: Discussionmentioning

confidence: 99%

Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

Foss

Bedja

Mease

et al. 2015

Biochemical and Biophysical Research Communications

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Background Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and Results We previously developed a low-molecular-weight imaging agent, [125I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE−/− mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE−/− mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions IodoDPA is a promising, new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved.

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Imaging of carrageenan-induced local inflammation and adjuvant-induced systemic arthritis with [11C]PBR28 PET

Cited by 21 publications

References 43 publications

Comparative Evaluation of Three TSPO PET Radiotracers in a LPS-Induced Model of Mild Neuroinflammation in Rats

Comparative Evaluation of Three TSPO PET Radiotracers in a LPS-Induced Model of Mild Neuroinflammation in Rats

The immune response of the human brain to abdominal surgery

Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

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