Increased Binding of Peripheral Benzodiazepine Receptor in Alzheimer's Disease Measured by Positron Emission Tomography with [11C]DAA1106

Yasuno, Fumihiko; Ota, Miho; Kosaka, Jun; Ito, Hiroshi; Higuchi, Makoto; Doronbekov, Talant K.; Nozaki, Shinichi; Fujimura, Yota; Koeda, Michihiko; Asada, Takashi; Suhara, Tetsuya

doi:10.1016/j.biopsych.2008.04.021

Cited by 200 publications

(153 citation statements)

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“…Translocator protein is an outer mitochondrial membrane which has long been considered as a component of the mPTP and which regulates mitochondria‐mediated apoptotic cell death (Gatliff & Campanella, 2012; Morin, Musman, Pons, Berdeaux, & Ghaleh, 2016). Translocator protein expression is increased in elderly people and in patients with Alzheimer's disease (Kumar et al., 2012; Yasuno et al., 2008). Interestingly, inhibition of TSPO in drosophila inhibited apoptosis, extended fly lifespan, and inhibited Aβ peptide‐induced neurodegeneration (Lin et al., 2014).…”

Section: Evidence For the Involvement Of Mptp Opening In Age‐associatmentioning

confidence: 99%

Mitochondria and aging: A role for the mitochondrial transition pore?

2018

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SummaryThe cellular mechanisms responsible for aging are poorly understood. Aging is considered as a degenerative process induced by the accumulation of cellular lesions leading progressively to organ dysfunction and death. The free radical theory of aging has long been considered the most relevant to explain the mechanisms of aging. As the mitochondrion is an important source of reactive oxygen species (ROS), this organelle is regarded as a key intracellular player in this process and a large amount of data supports the role of mitochondrial ROS production during aging. Thus, mitochondrial ROS, oxidative damage, aging, and aging‐dependent diseases are strongly connected. However, other features of mitochondrial physiology and dysfunction have been recently implicated in the development of the aging process. Here, we examine the potential role of the mitochondrial permeability transition pore (mPTP) in normal aging and in aging‐associated diseases.

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Section: Evidence For the Involvement Of Mptp Opening In Age‐associatmentioning

confidence: 99%

Mitochondria and aging: A role for the mitochondrial transition pore?

2018

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“…In vivo studies demonstrated that these ligands had higher uptake and specific binding in rodent and primate brains than did 11 C-PK11195 (22)(23)(24). We have reported a kinetic analysis method for 11 C-DAA1106 and 18 F-FEDAA1106 binding in the human brain (26,27) and a broad increase of PBR binding in the Alzheimer disease brain using 11 C-DAA1106 (28).…”

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confidence: 99%

Quantitative Analysis of Peripheral Benzodiazepine Receptor in the Human Brain Using PET with ¹¹C-AC-5216

Miyoshi¹,

Ito²,

Arakawa³

et al. 2009

J Nucl Med

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Peripheral benzodiazepine receptor (PBR) is upregulated in activated glial cells and is therefore a useful biomarker for inflammation in the brain and neurodegenerative disorders. We developed a new PET radioligand, 11 C-AC-N-benzyl-N-ethyl-2-(7-methyl-8-oxo-2-pheyl-7,8-dihydro-9H-purin-9-yl)acetamide ( 11 C-AC-5216), that allows the imaging and quantification of PBRs in monkey and mouse brains. The aim of this study was to evaluate a quantification method of 11 C-AC-5216 binding in the human brain. Methods: A 90-min dynamic PET scan was obtained for each of 12 healthy men after an intravenous injection of 11 C-AC-5216. Regions of interest were drawn on several brain regions. Binding potential, compared with nondisplaceable uptake (BP ND ), was calculated by a nonlinear least-squares fitting (NLS) method with the 2-tissue-compartment model, and total volume of distribution (V T ) was estimated by NLS and graphical analysis methods. Results: BP ND was highest in the thalamus (4.6 6 1.0) and lowest in the striatum (3.5 6 0.7). V T obtained by NLS or graphical analysis showed regional distribution similar to BP ND . However, there was no correlation between BP ND and V T because of the interindividual variation of K 1 /k 2 . BP ND obtained with data from a scan time of 60 min was in good agreement with that from a scan time of 90 min (r 5 0.87). Conclusion: Regional distribution of 11 C-AC-5216 was in good agreement with previous PET studies of PBRs in the human brain. BP ND is more appropriate for estimating 11 C-AC-5216 binding than is V T because of the interindividual variation of K 1 /k 2 . 11 C-AC-5216 is a promising PET ligand for quantifying PBR in the human brain.

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“…In the brain, TSPO is located mainly in glial cells, and TSPO expression was increased in microglial cells activated by brain injury or neuroinflammation (4-7). Neuropathologic evidence has demonstrated that an increase in TSPO and concurrent microglial and astroglial activation accompanies the neurodegenerative process in Alzheimer disease (7)(8)(9). These findings motivated the development of imaging probes labeled by positron-emitting radionuclides and have enabled visualization of the distribution and change in TSPO induced by microglial activation in normal and abnormal brains of humans and animals (10)(11)(12)(13)(14)(15)(16)(17)(18).…”

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confidence: 99%

¹⁸F-FEAC and ¹⁸F-FEDAC: PET of the Monkey Brain and Imaging of Translocator Protein (18 kDa) in the Infarcted Rat Brain

Yui¹,

Maeda²,

Kumata³

et al. 2010

J Nucl Med

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We evaluated two F-fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl] acetamide ( 18 F-FEAC) and N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-18 F-fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide ( 18 F-FEDAC), by investigating their kinetics in the monkey brain and by performing in vitro and in vivo imaging of translocator protein (18 kDa) (TSPO) in the infarcted rat brain. Methods: Dissection was used to determine the distribution of 18 F-FEAC and 18 F-FEDAC in mice, whereas PET was used for a monkey. With each 18 F-ligand, in vitro autoradiography and small-animal PET were performed on infarcted rat brains. Results: 18 F-FEAC and 18 F-FEDAC had a high uptake of radioactivity in the heart, lung, and other TSPO-rich organs of mice. In vitro autoradiography showed that the binding of each 18 F-ligand significantly increased on the ipsilateral side of rat brains, compared with the contralateral side. In a smallanimal PET study, PET summation images showed the contrast of radioactivity between ipsilateral and contralateral sides. Pretreatment with TSPO ligands N-benzyl-N-ethyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl) acetamide (AC-5216) or (R)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide (PK11195) diminished the difference in uptake between the 2 sides. The PET study showed that each 18 F-ligand had uptake and distribution patterns in the monkey brain similar to those of 11 C-AC-5216. After injection into the monkey during PET, the uptake of each 18 F-ligand in the brain decreased over time whereas 11 C-AC-5216 did not. In the brain homogenate of mice, the percentage of the fraction corresponding to intact 18 F-FEAC and 18 F-FEDAC was 68% and 75% at 30 min after injection. In monkey plasma, each 18 F-ligand was scarcely metabolized until the end of the PET scan. Conclusion: 18 F-FEAC and 18 F-FEDAC produced in vitro and in vivo signals allowing visualization of the increase in TSPO expression in the infarcted rat brain. The kinetics of both 18 F-ligands in the monkey brain and tolerance for in vivo metabolism suggested their usefulness for imaging studies of TSPO in primates.

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Increased Binding of Peripheral Benzodiazepine Receptor in Alzheimer's Disease Measured by Positron Emission Tomography with [11C]DAA1106

Cited by 200 publications

References 45 publications

Mitochondria and aging: A role for the mitochondrial transition pore?

Mitochondria and aging: A role for the mitochondrial transition pore?

Quantitative Analysis of Peripheral Benzodiazepine Receptor in the Human Brain Using PET with ¹¹C-AC-5216

¹⁸F-FEAC and ¹⁸F-FEDAC: PET of the Monkey Brain and Imaging of Translocator Protein (18 kDa) in the Infarcted Rat Brain

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Increased Binding of Peripheral Benzodiazepine Receptor in Alzheimer's Disease Measured by Positron Emission Tomography with [11C]DAA1106

Cited by 200 publications

References 45 publications

Mitochondria and aging: A role for the mitochondrial transition pore?

Mitochondria and aging: A role for the mitochondrial transition pore?

Quantitative Analysis of Peripheral Benzodiazepine Receptor in the Human Brain Using PET with 11C-AC-5216

18F-FEAC and 18F-FEDAC: PET of the Monkey Brain and Imaging of Translocator Protein (18 kDa) in the Infarcted Rat Brain

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Quantitative Analysis of Peripheral Benzodiazepine Receptor in the Human Brain Using PET with ¹¹C-AC-5216

¹⁸F-FEAC and ¹⁸F-FEDAC: PET of the Monkey Brain and Imaging of Translocator Protein (18 kDa) in the Infarcted Rat Brain