Translocator protein (18 kDa), a potential molecular imaging biomarker for non-invasively distinguishing non-alcoholic fatty liver disease

Xie, Lin; Yui, Joji; Hatori, Akiko; Yamasaki, Tomoteru; Kumata, Katsushi; Wakizaka, Hidekatsu; Yoshida, Yuichiro; Fujinaga, Masayuki; Kawamura, Kazunori; Zhang, Ming‐Rong

doi:10.1016/j.jhep.2012.07.002

Cited by 58 publications

(81 citation statements)

References 28 publications

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“…Analysis association between 18 F-FEDAC binding and NAFLD activity score is in consonance with in vitro findings where TSPO overexpression was reported in activated hepatic stellate cells [81] and in the adipocytes of stressed rats with adipocytes aggregates and neoangiogenesis process [82]. TSPO PET tracer uptake increased in parallel with liver disease severity whether it is in NAFLD [79] or in fibrosis liver models [80]. Positively correlation between hepatic TSPO and (transforming growth factor) TGF- β 1/(tumor necrosis factor) TNF- α mRNA expression [80] suggests that macrophage M1 and M2 phenotypes intervene during liver fibrosis development [83].…”

Section: Tspo Pet Imaging Of Psidssupporting

confidence: 81%

“…Tissue analysis revealed more serious steatotic aggregates and necroinflammatory infiltration in the higher uptake region of 18 F-FEDAC. Autoradiography experiments [79, 80] supported in vivo PET data where TSPO tracer binding was not homogeneously distributed in the livers with nonalcoholic fatty liver disease (NAFLD) [79] and in the fibrotic livers (induced by carbon tetrachloride treatment) [80]. Analysis association between 18 F-FEDAC binding and NAFLD activity score is in consonance with in vitro findings where TSPO overexpression was reported in activated hepatic stellate cells [81] and in the adipocytes of stressed rats with adipocytes aggregates and neoangiogenesis process [82].…”

Section: Tspo Pet Imaging Of Psidsmentioning

confidence: 99%

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TSPO PET Imaging: From Microglial Activation to Peripheral Sterile Inflammatory Diseases?

Largeau

Dupont

Guilloteau

et al. 2017

Contrast Media & Molecular Imaging

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Peripheral sterile inflammatory diseases (PSIDs) are a heterogeneous group of disorders that gathers several chronic insults involving the cardiovascular, respiratory, gastrointestinal, or musculoskeletal system and wherein inflammation is the cornerstone of the pathophysiology. In PSID, timely characterization and localization of inflammatory foci are crucial for an adequate care for patients. In brain diseases, in vivo positron emission tomography (PET) exploration of inflammation has matured over the last 20 years, through the development of radiopharmaceuticals targeting the translocator protein-18 kDa (TSPO) as molecular biomarkers of activated microglia. Recently, TSPO has been introduced as a possible molecular target for PSIDs PET imaging, making this protein a potential biomarker to address disease heterogeneity, to assist in patient stratification, and to contribute to predicting treatment response. In this review, we summarized the major research advances recently made in the field of TSPO PET imaging in PSIDs. Promising preliminary results have been reported in bowel, cardiovascular, and rheumatic inflammatory diseases, consolidated by preclinical studies. Limitations of TSPO PET imaging in PSIDs, regarding both its large expression in healthy peripheral tissues, unlike in central nervous system, and the production of peripheral radiolabeled metabolites, are also discussed, regarding their possible consequences on TSPO PET signal's quantification.

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Section: Tspo Pet Imaging Of Psidssupporting

confidence: 81%

Section: Tspo Pet Imaging Of Psidsmentioning

confidence: 99%

TSPO PET Imaging: From Microglial Activation to Peripheral Sterile Inflammatory Diseases?

Largeau

Dupont

Guilloteau

et al. 2017

Contrast Media & Molecular Imaging

View full text Add to dashboard Cite

show abstract

“…Simple steatosis without fibrosis or inflammation has a benign clinical course in most but not in all cases without excess mortality [3]. NASH, on the other hand, may have a more progressive course that can lead to cirrhosis in 10-15% of patients [4]. Survival is lower in patients with NASH based on the findings from long-term longitudinal studies [3,5].…”

Section: Introductionmentioning

confidence: 99%

Noninvasive biomarkers for the diagnosis of steatohepatitis and advanced fibrosis in NAFLD

2013

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Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver enzymes in both adults and children. NAFLD has a histologic spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. It is imperative to distinguish simple steatosis from NASH since the latter has a progressive disease course and can lead to end-stage liver disease. Liver biopsy has been considered as the gold standard for the diagnosis of NASH. However, liver biopsy is invasive, costly, and can rarely cause significant morbidity (risk of morbidity, 0.06-0.35%; risk of mortality, 0.1-0.01%). Imaging studies such as ultrasonography, computed tomography, and magnetic resonance imaging have limited sensitivity in detecting steatosis and cannot distinguish steatosis from NASH. Alanine aminotransferase (ALT) has been used as a surrogate marker for liver injuries. However, ALT is not an ideal marker for either diagnosis of NAFLD or distinguishing steatosis from NASH. Better noninvasive biomarkers or panels of biomarkers that are cheaper, reliable, and reproducible are urgently needed for patients with NASH to assist in establishing diagnosis, providing risk information, and monitoring disease progression and treatment response. In this article, we plan to concisely review the current advances in the use of biomarkers for the diagnosis of NASH.

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“…This protein is up-regulated in inflammatory processes, making radiolabeled TSPO ligands attractive imaging probes in a multitude of pathologies. Different TSPO ligands have already been used as imaging probes in different animal models of human diseases such as cancer [16], cerebral ischemia [17], lung [18] and liver diseases [19]. …”

Section: Introductionmentioning

confidence: 99%

“…For the moment, [ 18 F]DPA-714 is mainly used to image brain injury in various animal models [17,24-26] but also in the field of oncology with applications in breast cancer [27] and glioma [28]. Interest for the molecular imaging of peripheral inflammation has also been investigated recently in non-alcoholic fatty liver disease in rats [19] and lungs by the same team [18] using another radiolabelled TSPO ligand ([ 18 F]FEDAC). Recently, [ 11 C]PK11195 has been shown to be of potential interest in imaging arthritis in humans [7,10,29].…”

Section: Introductionmentioning

confidence: 99%

[18F]DPA-714 as a biomarker for positron emission tomography imaging of rheumatoid arthritis in an animal model

et al. 2014

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IntroductionRheumatoid arthritis (RA) is a chronic disease, affecting 0.5 to 1% of adults in industrialized countries, in which systemic inflammation and synovitis drive joint destruction. [18F]DPA-714 is a specific tracer of the 18 kDa translocator protein (TSPO), which is overexpressed on activated macrophages, and proposed as a biomarker of neuroinflammation. Today, diagnosis of patients with early inflammatory arthritis is limited by poor sensitivity and specificity. The present study aims to investigate the potential of [18F]DPA-714 to monitor in vivo inflammatory processes at a preclinical stage via positron emission tomography (PET).MethodsRA was induced in Dark Agouti rats by subcutaneous injection of inactivated Mycobacterium tuberculosis. Development of arthritis clinical signs was investigated daily and the severity of the disease evaluated. Animals were imaged at the peak of inflammation using [18F]DPA-714 and a small-animal PET-CT tomograph.ResultsThe first clinical signs appeared at 10 days post-injection, with a peak of inflammation at 20 days. At this time, PET-analyses showed a clear uptake of [18F]DPA-714 in swollen ankles, with mean values of 0.52 ± 0.18% injected dose (ID/cc) for treated (n = 11) and 0.19 ± 0.09 for non-treated (n = 6) rats. A good correlation between [18F]DPA-714’s uptake and swelling was also found. Immunohistochemistry showed an enhanced TSPO expression in hind paws, mainly co-localized with the macrophages specific antigen CD68 expressing cells.ConclusionThese preliminary results demonstrate that the TSPO 18kDa specific radioligand [18F]DPA-714 is adapted for the study and follow-up of inflammation linked to RA in our experimental model, suggesting also a strong potential for clinical imaging of peripheral inflammation.

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Translocator protein (18 kDa), a potential molecular imaging biomarker for non-invasively distinguishing non-alcoholic fatty liver disease

Cited by 58 publications

References 28 publications

TSPO PET Imaging: From Microglial Activation to Peripheral Sterile Inflammatory Diseases?

TSPO PET Imaging: From Microglial Activation to Peripheral Sterile Inflammatory Diseases?

Noninvasive biomarkers for the diagnosis of steatohepatitis and advanced fibrosis in NAFLD

[18F]DPA-714 as a biomarker for positron emission tomography imaging of rheumatoid arthritis in an animal model

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