PET/SPECT Molecular Probes for the Diagnosis and Staging of Nonalcoholic Fatty Liver Disease

Shao, Tuo; Josephson, Lee; Liang, Steven H.

doi:10.1177/1536012119871455

Cited by 12 publications

(10 citation statements)

References 57 publications

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“…While several of the widely used serum marker panels include assays for matrix molecules or their fragments, the mechanisms underlying their release into the blood and circulating levels are not well characterized, and thus their biologic plausibility is not fully established. On the other hand, specific imaging of hepatic collagen or other ECM constituents [ 102 ] may enable a more direct assessment of their content in liver. Functional reserve and regeneration ? As noted above, the liver is a functionally rich organ regulating myriad metabolic and homeostatic functions, with an unmatched secretome, and thus continued efforts to capture functional readouts of liver health and disease demand further investment.…”

Section: Noninvasive Assessment Of Hepatic Fibrosismentioning

confidence: 99%

Hepatic fibrosis 2022: Unmet needs and a blueprint for the future

2022

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Steady progress over four decades toward understanding the pathogenesis and clinical consequences of hepatic fibrosis has led to the expectation of effective antifibrotic drugs, yet none has been approved. Thus, an assessment of the field is timely, to clarify priorities and accelerate progress. Here, we highlight the successes to date but, more importantly, identify gaps and unmet needs, both experimentally and clinically. These include the need to better define cell-cell interactions and etiology-specific elements of fibrogenesis and their link to disease-specific drivers of portal hypertension. Success in treating viral hepatitis has revealed the remarkable capacity of the liver to degrade scar in reversing fibrosis, yet we know little of the mechanisms underlying this response. Thus, there is an exigent need to clarify the cellular and molecular mechanisms of fibrosis regression in order for therapeutics to mimic the liver's endogenous capacity. Better refined and more predictive in vitro and animal models will hasten drug development. From a clinical perspective, current diagnostics are improving but not always biologically plausible or sufficiently accurate to supplant biopsy. More urgently, digital pathology methods that leverage machine learning and artificial intelligence must be validated in order to capture more prognostic information from liver biopsies and better quantify the response to therapies. For more refined treatment of NASH, orthogonal approaches that integrate genetic, clinical, and pathological data sets may yield treatments for specific subphenotypes of the disease.Collectively, these and other advances will strengthen and streamline clinical trials and better link histologic responses to clinical outcomes.

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Section: Noninvasive Assessment Of Hepatic Fibrosismentioning

confidence: 99%

Hepatic fibrosis 2022: Unmet needs and a blueprint for the future

2022

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“…The existence of different ligands inside integrins (i.e., fibronectin, vitronectin, collagen, and laminin) has led researchers to real-time monitoring of cells, singlephoton emission tomography (SPECT), and positron emission tomography (PET). [41][42][43][44] Integrin receptors, which have been studied for 20 years, have recently been utilized in theranostic applications. [45] Shi et al [46] initiated designing AIEgen bioprobes fitted with a targeting ligand to integrin motifs.…”

Section: Integrinmentioning

confidence: 99%

AIEgen‐enhanced protein imaging: Probe design and sensing mechanisms

et al. 2021

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Proteins are the building blocks of life, regarded as one of the most complex and crucial biomacromolecules in biological systems, and playing a significant role in executing genes and transferring genetic information. According to recent research, due to the structural intricacy of proteins and their sensitivity to physical and chemical degradation processes, they could be utilized as biomarkers or therapeutic agents in the diagnosis, treatment, or even prevention of different diseases. Therefore, modern pathways have been developed for understanding the function of proteins, resulting in intriguing approaches in the field of protein‐related diseases. The diagnostic strategies to deal with such diseases, including protein analysis, protein quantification, and protein imaging, were argued in depth. Meanwhile, the aggregation‐induced emission (AIE) concept and its potential applications for real‐time imaging make AIE luminogens (AIEgen) attractive for protein imaging. In general, AIEgens refer to those luminogenic chemicals that are nonluminescent in solution, but luminescent in either the aggregated or solid states. This review is focused on the emergence of AIE materials in protein tracking, detecting, and imaging for medical applications.

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“…As scarring progresses, subsequent growth of nodules from regenerating hepatocytes results in ultimately liver cirrhosis, which is the end consequence of progressive fibrosis and attended by high morbidity and mortality. Because patients with liver fibrosis are at high risk for the development of cirrhosis, the use of non-invasive imaging modalities such as molecularly targeted positron emission tomography (PET) to detect early stage liver fibrosis and/or monitor targeted therapy at the cellular level may be of great translational value 3 . Until now, liver biopsy has been the gold standard for identifying liver fibrosis but has well-known limitations.…”

Section: Introductionmentioning

confidence: 99%

[18F]MAGL-4-11 positron emission tomography molecular imaging of monoacylglycerol lipase changes in preclinical liver fibrosis models

Shao

Chen

Rong

et al. 2022

Acta Pharmaceutica Sinica B

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Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an 18 F-labeled MAGL inhibitor ([ 18 F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo . In this study, we determined [ 18 F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl 4 ) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [ 18 F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [ 18 F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [ 18 F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [ 18 F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.

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PET/SPECT Molecular Probes for the Diagnosis and Staging of Nonalcoholic Fatty Liver Disease

Cited by 12 publications

References 57 publications

Hepatic fibrosis 2022: Unmet needs and a blueprint for the future

Hepatic fibrosis 2022: Unmet needs and a blueprint for the future

AIEgen‐enhanced protein imaging: Probe design and sensing mechanisms

[18F]MAGL-4-11 positron emission tomography molecular imaging of monoacylglycerol lipase changes in preclinical liver fibrosis models

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