In vivo imaging and quantitative analysis of TSPO in rat peripheral tissues using small-animal PET with [18F]FEDAC

Yanamoto, Kazuhiko; Kumata, Katsushi; Fujinaga, Masayuki; Nengaki, Nobuki; Takei, Makoto; Wakizaka, Hidekatsu; Hosoi, Rie; Momosaki, Sotaro; Yamasaki, Tomoteru; Yui, Joji; Kawamura, Kazunori; Hatori, Akiko; Ito, Osamu; Zhang, Ming‐Rong

doi:10.1016/j.nucmedbio.2010.04.183

Cited by 19 publications

(25 citation statements)

References 33 publications

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“…Several PET studies using [ 18 F] FEDAC in rodent models have shown in vivo specific binding with TSPO and high radioactive signals in TSPO‐rich organs . In contrast, the uptake of [ 18 F] FEDAC in healthy CNS is reported to be much lower . Therefore, PET with [ 18 F] FEDAC has the potential to detect early CNS disorders related to TSPO.…”

Section: Discussionmentioning

confidence: 99%

In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation

Tanimoto

Yamasaki

Nagoshi

et al. 2020

Stem Cells Translational Medicine

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Transplantation of human‐induced pluripotent stem cell‐derived neural stem/progenitor cells (hiPSC‐NS/PCs) is a promising treatment for a variety of neuropathological conditions. Although previous reports have indicated the effectiveness of hiPSC‐NS/PCs transplantation into the injured spinal cord of rodents and nonhuman primates, long‐term observation of hiPSC‐NS/PCs post‐transplantation suggested some “unsafe” differentiation‐resistant properties, resulting in disordered overgrowth. These findings suggest that, even if “safe” NS/PCs are transplanted into the human central nervous system (CNS), the dynamics of cellular differentiation of stem cells should be noninvasively tracked to ensure safety. Positron emission tomography (PET) provides molecular‐functional information and helps to detect specific disease conditions. The current study was conducted to visualize Nestin (an NS/PC marker)‐positive undifferentiated neural cells in the CNS of immune‐deficient (nonobese diabetic‐severe combined immune‐deficient) mice after hiPSC‐NS/PCs transplantation with PET, using 18 kDa translocator protein (TSPO) ligands as labels. TSPO was recently found to be expressed in rodent NS/PCs, and its expression decreased with the progression of neuronal differentiation. We hypothesized that TSPO would also be present in hiPSC‐NS/PCs and expressed strongly in residual immature neural cells after transplantation. The results showed high levels of TSPO expression in immature hiPSC‐NS/PCs‐derived cells, and decreased TSPO expression as neural differentiation progressed in vitro. Furthermore, PET with [18F] FEDAC (a TSPO radioligand) was able to visualize the remnant undifferentiated hiPSC‐NS/PCs‐derived cells consisting of TSPO and Nestin+ cells in vivo. These findings suggest that PET with [18F] FEDAC could play a key role in the safe clinical application of CNS repair in regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation

Tanimoto

Yamasaki

Nagoshi

et al. 2020

Stem Cells Translational Medicine

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“…PET with [ 18 F]FEDAC in normal rats has shown high in vivo specific binding for TSPO and high radioactive signals in the TSPO-enriching adrenal gland, lung, heart, and kidney [19]. On the other hand, the uptakes of [ 18 F]FEDAC in liver and blood were much lower than that in lung, showing that the imaging of peripheral organs could not disturbed by the liver and blood uptakes.…”

Section: Discussionmentioning

confidence: 99%

PET Imaging of Lung Inflammation with [18F]FEDAC, a Radioligand for Translocator Protein (18 kDa)

Hatori¹,

Yui²,

Yamasaki³

et al. 2012

PLoS ONE

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PurposeThe translocator protein (18 kDa) (TSPO) is highly expressed on the bronchial and bronchiole epithelium, submucosal glands in intrapulmonary bronchi, pneumocytes and alveolar macrophages in human lung. This study aimed to perform positron emission tomography (PET) imaging of lung inflammation with [18F]FEDAC, a specific TSPO radioligand, and to determine cellular sources enriching TSPO expression in the lung.MethodsAn acute lung injury model was prepared by intratracheal administration of lipopolysaccharide (LPS) to rat. Uptake of radioactivity in the rat lungs was measured with small-animal PET after injection of [18F]FEDAC. Presence of TSPO was examined in the lung tissue using Western blot and immunohistochemical assays.ResultsThe uptake of [18F]FEDAC increased in the lung with the progress of inflammation by treatment with LPS. Pretreatment with a TSPO-selective ligand PK11195 showed a significant decrease in the lung uptake of [18F]FEDAC due to competitive binding to TSPO. TSPO expression was elevated in the inflamed lung section and its level responded to the [18F]FEDAC uptake and severity of inflammation. Increase of TSPO expression was mainly found in the neutrophils and macrophages of inflamed lungs.ConclusionFrom this study we conclude that PET with [18F]FEDAC may be a useful tool for imaging TSPO expression and evaluating progress of lung inflammation. Study on human lung using [18F]FEDAC-PET is promising.

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“…TSPO up-regulation is considered a hallmark of neuroinflammation (Rivera 2001). Radiolabeled imaging agents have permitted sensitive detection of TSPO when applied to autoradiographic and positron emission tomography (PET) techniques (Zhang et al 2007a, b;Yanamoto et al 2010;. It has been reported that [ 11 C] PK11195, the most commonly used TSPO probe, increased binding in patients with stroke (Chauveau et al 2009;Thiel et al 2010) and traumatic brain injury (Toyama et al 2008;Folkersma et al 2009), and in patients with chronic neurodegenerative conditions, including Huntington's disease Tai et al 2007), Parkinson's disease Bartels and Leenders 2007) and MS (Agnello et al 2000;Banati et al 2000).…”

Section: Introductionmentioning

confidence: 99%

[11C]DAC-PET for Noninvasively Monitoring Neuroinflammation and Immunosuppressive Therapy Efficacy in Rat Experimental Autoimmune Encephalomyelitis Model

Xie

Yamasaki

Ichimaru

et al. 2011

J Neuroimmune Pharmacol

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Neuroimaging measures have potential for monitoring neuroinflammation to guide treatment before the occurrence of significant functional impairment or irreversible neuronal damage in multiple sclerosis (MS). N-Benzyl-N-methyl-2-(7-[(11)C]methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl) acetamide ([(11)C]DAC), a new developed positron emission tomography (PET) probe for translocator protein 18 kDa (TSPO), has been adopted to evaluate the neuroinflammation and treatment effects of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. [(11)C]DAC-PET enabled visualization of neuroinflammation lesion of EAE by tracing TSPO expression in the spinal cords; the maximal uptake value reached in day 11 and 20 EAE rats with profound inflammatory cell infiltration compared with control, day 0 and 60 EAE rats. Biodistribution studies and in vitro autoradiography confirmed these in vivo imaging results. Doubling immunohistochemical studies showed the infiltration and expansion of CD4+ T cells and CD11b+ microglia; CD68+ macrophages were responsible for the increased TSPO levels visualized by [(11)C]DAC-PET. Furthermore, mRNA level analysis of the cytokines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) revealed that TSPO+/CD4 T cells, TSPO+ microglia and TSPO+ macrophages in EAE spinal cords were activated and secreted multiple proinflammation cytokines to mediate inflammation lesions of EAE. EAE rats treated with an immunosuppressive agent: 2-amino-2-[2-(4-octylphenyl)ethyl] propane-1,3-diolhydrochloride (FTY720), which exhibited an absence of inflammatory cell infiltrates, displaying a faint radioactive signal compared with the high accumulation of untreated EAE rats. These results indicated that [(11)C] DAC-PET imaging is a sensitive tool for noninvasively monitoring the neuroinflammation response and evaluating therapeutic interventions in EAE.

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In vivo imaging and quantitative analysis of TSPO in rat peripheral tissues using small-animal PET with [18F]FEDAC

Cited by 19 publications

References 33 publications

In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation

In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation

PET Imaging of Lung Inflammation with [18F]FEDAC, a Radioligand for Translocator Protein (18 kDa)

[11C]DAC-PET for Noninvasively Monitoring Neuroinflammation and Immunosuppressive Therapy Efficacy in Rat Experimental Autoimmune Encephalomyelitis Model

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