Graphic plot analysis for estimating binding potential of translocator protein (TSPO) in positron emission tomography studies with [18F]FEDAA1106

NeuroImage ◽  
2013 ◽  
Vol 69 ◽  
pp. 78-86 ◽  
Author(s):  
Yoko Ikoma ◽  
Akihiro Takano ◽  
Andrea Varrone ◽  
Christer Halldin
Keyword(s):  
Positron Emission Tomography ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Plot Analysis ◽  
Positron Emission

scholarly journals Quantitation of Translocator Protein Binding in Human Brain with the Novel Radioligand [18F]-FEPPA and Positron Emission Tomography

2011 ◽  
Vol 31 (8) ◽  
pp. 1807-1816 ◽  
Author(s):  
Pablo M Rusjan ◽  
Alan A Wilson ◽  
Peter M Bloomfield ◽  
Irina Vitcu ◽  
Jeffrey H Meyer ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Brain ◽  
Specific Binding ◽  
Compartment Model ◽  
Distribution Volume ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Specific Distribution ◽  
Positron Emission

This article describes the kinetic modeling of [18F]-FEPPA binding to translocator protein 18 kDa in the human brain using high-resolution research tomograph (HRRT) positron emission tomography. Positron emission tomography scans were performed in 12 healthy volunteers for 180 minutes. A two-tissue compartment model (2-CM) provided, with no exception, better fits to the data than a one-tissue model. Estimates of total distribution volume ( VT), specific distribution volume ( VS), and binding potential ( BPND) demonstrated very good identifiability (based on coefficient of variation ( COV)) for all the regions of interest (ROIs) in the gray matter ( COV VT < 7%, COV VS < 8%, COV BPND < 11%). Reduction of the length of the scan to 2 hours is feasible as VS and VT showed only a small bias (6% and 7.5%, respectively). Monte Carlo simulations showed that, even under conditions of a 500% increase in specific binding, the identifiability of VT and VS was still very good with COV<10%, across high-uptake ROIs. The excellent identifiability of VT values obtained from an unconstrained 2-CM with data from a 2-hour scan support the use of VT as an appropriate and feasible outcome measure for [18F]-FEPPA.

scholarly journals 11C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than 11C-(R)-PK11195

2017 ◽  
Vol 38 (3) ◽  
pp. 393-403 ◽  
Author(s):  
Masato Kobayashi ◽  
Teresa Jiang ◽  
Sanjay Telu ◽  
Sami S Zoghbi ◽  
Roger N Gunn ◽  
...  
Keyword(s):  
Second Generation ◽  
Specific Binding ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Arterial Blood ◽  
Plot Analysis ◽  
Positron Emission ◽  
Translocator Protein 18 Kda ◽  
Pet Scans

Positron emission tomography (PET) radioligands for translocator protein 18 kDa (TSPO) are widely used to measure neuroinflammation, but controversy exists whether second-generation radioligands are superior to the prototypical agent 11C-( R)-PK11195 in human imaging. This study sought to quantitatively measure the “signal to background” ratio (assessed as binding potential ( BPND)) of 11C-( R)-PK11195 compared to one of the most promising second-generation radioligands, 11C-DPA-713. Healthy subjects had dynamic PET scans and arterial blood measurements of radioligand after injection of either 11C-( R)-PK11195 (16 subjects) or 11C-DPA-713 (22 subjects). To measure the amount of specific binding, a subset of these subjects was scanned after administration of the TSPO blocking drug XBD173 (30–90 mg PO). 11C-DPA-713 showed a significant sensitivity to genotype in brain, whereas 11C-( R)-PK11195 did not. Lassen occupancy plot analysis revealed that the specific binding of 11C-DPA-713 was much greater than that of 11C-( R)-PK11195. The BPND in high-affinity binders was about 10-fold higher for 11C-DPA-713 (7.3) than for 11C-( R)-PK11195 (0.75). Although the high specific binding of 11C-DPA-713 suggests it is an ideal ligand to measure TSPO, we also found that its distribution volume increased over time, consistent with the accumulation of radiometabolites in brain.

scholarly journals Depiction of microglial activation in aging and dementia: Positron emission tomography with [11C]DPA713 versus [11C](R)PK11195

2016 ◽  
Vol 37 (3) ◽  
pp. 877-889 ◽  
Author(s):  
Masamichi Yokokura ◽  
Tatsuhiro Terada ◽  
Tomoyasu Bunai ◽  
Kyoko Nakaizumi ◽  
Kiyokazu Takebayashi ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Microglial Activation ◽  
Second Generation ◽  
Neuronal Degeneration ◽  
Brain Regions ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Healthy Elderly ◽  
Positron Emission

The presence of activated microglia in the brains of healthy elderly people is a matter of debate. We aimed to clarify the degree of microglial activation in aging and dementia as revealed by different tracers by comparing the binding potential (BPND) in various brain regions using a first-generation translocator protein (TSPO) tracer [11C]( R)PK11195 and a second-generation tracer [11C]DPA713. The BPND levels, estimated using simplified reference tissue models, were compared among healthy young and elderly individuals and patients with Alzheimer’s disease (AD) and were correlated with clinical scores. An analysis of variance showed category-dependent elevation in levels of [11C]DPA713 BPND in all brain regions and showed a significant increase in the AD group, whereas no significant changes among groups were found when [11C]( R)PK11195 BPND was used. Cognito-mnemonic scores were significantly correlated with [11C]DPA713 BPND levels in many brain regions, whereas [11C]( R)PK11195 BPND failed to correlate with the scores. As mentioned elsewhere, the present results confirmed that the second-generation TSPO tracer [11C]DPA713 has a greater sensitivity to TSPO in both aging and neuronal degeneration than [11C]( R)PK11195. Positron emission tomography with [11C]DPA713 is suitable for the delineation of in vivo microglial activation occurring globally over the cerebral cortex irrespective of aging and degeneration.

scholarly journals [18F]FEDAC translocator protein positron emission tomography–computed tomography for early detection of mitochondrial dysfunction secondary to myocardial ischemia

2021 ◽  
Author(s):  
Rui Luo ◽  
Lei Wang ◽  
Fei Ye ◽  
Yan-Rong Wang ◽  
Wei Fang ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Positron Emission Tomography ◽  
Early Detection ◽  
Myocardial Ischemia ◽  
Mitochondrial Dysfunction ◽  
High Performance ◽  
Dynamic Imaging ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Positron Emission

Abstract Background This study aimed to evaluate the biodistribution and kinetics of [18F]FEDAC targeting the translocator protein TSPO in the myocardium, and to explore its use for the identification of mitochondrial dysfunction. We also assessed the feasibility of [18F]FEDAC for the early detection of mitochondrial dysfunction associated with myocardial ischemia (MI). Methods The radiochemical purity and stability of [18F]FEDAC were analyzed by radio-high-performance liquid chromatography (radio-HPLC). Its biodistribution and kinetics were evaluated by dissection and dynamic imaging using micro-positron emission tomography–computed tomography (micro-PET–CT) in healthy mice. [18F]FEDAC was also applied in an MI rat model and in sham-operated controls. Mitochondrial changes were observed by immunohistochemical staining and electron microscopy. Results Radioactivity levels (%ID/g) in the myocardium in normal mice, determined by [18F]FEDAC, were 8.32 ± 0.80 at 5 min and 2.40 ± 0.10 at 60 min. PET showed significantly decreased uptake by injured cardiac tissue in MI rats, with maximal normal-to-ischemic uptake ratios of 10.47 ± 3.03 (1.5 min) and 3.92 ± 1.12 (27.5 min) (P = 0.025). Immunohistochemistry confirmed that TSPO expression was decreased in MI rats. Mitochondrial ultrastructure demonstrated significant swelling and permeability. Conclusion [18F]FEDAC uptake is reduced in the injured myocardium, consistent with mitochondrial dysfunction. These results may provide new evidence to aid the early detection of mitochondrial dysfunction associated with myocardial ischemic injury.

A new graphic plot analysis for determination of neuroreceptor binding in positron emission tomography studies

NeuroImage ◽  
2010 ◽  
Vol 49 (1) ◽  
pp. 578-586 ◽  
Author(s):  
Hiroshi Ito ◽  
Takashi Yokoi ◽  
Yoko Ikoma ◽  
Miho Shidahara ◽  
Chie Seki ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Emission Tomography ◽  
Plot Analysis ◽  
Positron Emission

scholarly journals Effects of an Adenosine A2A Receptor Antagonist on Striatal Dopamine D2-Type Receptor Availability: A Randomized Control Study Using Positron Emission Tomography

2021 ◽  
Vol 15 ◽  
Author(s):  
Kyoji Okita ◽  
Koichi Kato ◽  
Yoko Shigemoto ◽  
Noriko Sato ◽  
Toshihiko Matsumoto ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Substance Use ◽  
Receptor Antagonist ◽  
Substance Use Disorders ◽  
Emission Tomography ◽  
Binding Potential ◽  
Dopamine D2 ◽  
Positron Emission ◽  
A2a Receptor ◽  
Type Receptor

Introduction: Altered dopaminergic neurotransmission, especially in the functioning of dopamine D2-type receptors, is considered central to the etiology of a variety of neuropsychiatric disorders. In particular, individuals with substance use disorders have been consistently observed to exhibit lower D2-type receptor availability (quantified as binding potential; BPND) using positron emission tomography (PET). Upregulation of D2-type receptor density thus may therefore provide a therapeutic effect for substance use disorders. Importantly, in vitro studies reveal that D2 receptors coexist with adenosine 2A (A2A) receptors to form the highest density of heteromers in the whole striatum, and there is a functional interaction between these two receptors. As such, blockade of A2A receptor’s function may prevent D2 receptor downregulation, yet no study has currently examined this hypothesis in humans.Methods and Analysis: This double-blind, randomized controlled trial aims to evaluate the effect of the A2A receptor antagonist istradefylline (compared to placebo) on both dopamine D2-type receptor availability in the human brain and on neuropsychological measurements of impulsivity. It is hypothesized that istradefylline will both increase striatal D2-type BPND and improve control of impulsivity more than placebo. Forty healthy participants, aged 20–65 with no history of psychiatric or neurological disorders, will be recruited and randomized into two groups and will undergo [11C]raclopride PET, once before and once after administration of either 40 mg/day istradefylline or placebo for 2 weeks. Neuropsychological measurements will be administered on the same days of the PET scans.Ethics and Dissemination: The study protocol was approved by the Certified Review Boards (CRB) of National Center of Neurology and Psychiatry (CR18-011) and prospectively registered with the Japan Registry of Clinical Trials (jRCTs031180131; https://jrct.niph.go.jp/latest-detail/jRCTs031180131). The findings of this study will be disseminated through peer reviewed scientific journals and conferences.Clinical Trial Registration:www.ClinicalTrials.gov, identifier jRCTs031180131.

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