cis-4-[18F]fluoro-L-proline Molecular Imaging Experimental Liver Fibrosis

Cao, Qi; Lü, Xin; Azad, Babak Behnam; Pomper, Martin G.; Smith, Mark M.; He, Jiang; Pi, Liya; Ren, Bin; Zhao, Ying; Sichani, Babak Saboury; Morris, Michael; Dilsizian, Vasken

doi:10.3389/fmolb.2020.00090

Cited by 8 publications

(10 citation statements)

References 49 publications

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“…However, slight differences in TAA compositions were also found between SFBP and HFBP. Proline and hydroxyproline (imino acid) accounted for~23% of the amino acid content of the collagen molecule [36]. In the present study, imino acid residue totaled 183.3 per 1000 total residue in SFBP, which was approximately 1.14 times higher than that of the HFBP (160.6).…”

Section: Proximate and Amino Acid Compositions Of Fbpmentioning

confidence: 44%

Steam Explosion-Assisted Extraction of Protein from Fish Backbones and Effect of Enzymatic Hydrolysis on the Extracts

Dong

Yan

Zhang

et al. 2021

Foods

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The development of an efficient pretreatment, prior to enzymatic hydrolysis, is a good strategy for the sustainable use of refractory fish byproducts. This study compared hydrothermal pretreatments at 159 °C for 2 min, followed by water extraction (steam explosion-assisted extraction, SE) and 121 °C for 70 min (hot-pressure extraction, HPE), for the recovery of proteins from fish backbones. The effect of enzymatic hydrolysis on the properties of the obtained fish bone protein (FBP) was also evaluated. The results demonstrated that FBP had high contents of protein (81.09–84.88 g/100 g) and hydroxyproline (70–82 residues/1000 residues). After hydrolysis with Flavourzyme, for 3 h, the FBP hydrolysates that were pretreated with SE (SFBP-H) exhibited a better degree of hydrolysis (DH) and nitrogen recovery (NR), and a higher level of umami taste free amino acids (151.50 mg/100 mL), compared with the HPE-treated samples. The obtained SFBP-H mainly distributed below 3000 Da and had strong scavenging effects on 1,1-diphenyl-2-picrylhydrazy (DPPH) (IC50 = 4.24 mg/mL) and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) (IC50 = 1.93 mg/mL) radicals. Steam explosion-assisted extraction is a promising route for recovering proteins from native fish bone materials, and improving the flavor and antioxidant activity of the hydrolysates.

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Section: Proximate and Amino Acid Compositions Of Fbpmentioning

confidence: 44%

Steam Explosion-Assisted Extraction of Protein from Fish Backbones and Effect of Enzymatic Hydrolysis on the Extracts

Dong

Yan

Zhang

et al. 2021

Foods

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“…In another study, [ 18 F]MAGL-4-11 demonstrated reduced PET signals in the early stages of fibrosis and further significantly decrease with disease progression compared with control mice (14). Previously, we identified a [18F]proline that could serve as a PET imaging biomarker for detecting early-stage liver fibrosis in an LPS-induced mice model (15). That study was not powered to stage liver fibrosis as the animals were only imaged at an early-stage time point.…”

Section: Introductionmentioning

confidence: 95%

Cis-4-[18F]fluoro-L-proline PET/CT molecular imaging quantifying liver collagenogenesis: No existing fibrotic deposition in experimental advanced-stage alcoholic liver fibrosis

Duan

Chen²,

Pi³

et al. 2022

Front. Nucl. Med.

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Background and purposeHeavy alcohol drinking-induced alcoholic fatty liver, steatohepatitis, and early-stage alcoholic liver fibrosis may progress to advanced-stage alcoholic liver fibrosis (AALF)/cirrhosis. The lack of non-invasive imaging techniques for the diagnosising collagenogenesis in activated hepatic stellate cells (HSCs) can lead to incurable liver fibrosis at the early reversible stage. Proline has been known as the most abundant amino acid of collagen type 1 synthesized by activated HSC with the transportation of proline transporter. cis-4-[18F]fluoro-L-proline ([18F]proline) was reported as a useful tool to quantify collagenogenesis in experimental alcoholic steatohepatitis. This study aims to use [18F]proline micro PET as non-invasive imaging to quantify liver collagenogenesis in HSC of experimental AALF.MethodsAALF model was set up by a modified Lieber-DeCarli liquid ethanol diet for 12 weeks along with intraperitoneal injection (IP) of CCl4 (0.5 ml/kg) between the 5th and 12th weeks. Controls were fed an isocaloric liquid diet and IP. PBS. In vitro [3H]proline uptake by HSCs isolated from livers was quantified using a liquid scintillation counter. Collagen type 1 production in HSCs culture medium was assayed by ELISA. Ex vivo liver collagen type 1 and proline transporter protein were compared between AALF rats (n = 8) and mice (n = 8). [3H]Proline uptake specificity in ex vivo liver tissues was tested using unlabeled proline and transporter inhibitor benztropine at different doses. Liver H&E, trichrome stain, and blood biochemistry were tested in rats and mice. In vivo, at varying times after instillation, dynamic and static [18F]proline micro PET/CT were done to quantify tracer uptake in AALF mice (n = 3). Correlation among liver collagen, liver SUVmax, normalized liver-to-brain ratio, normalized liver-to-thigh ratio, and fluoro-proline-induced collagen levels in ex vivo liver tissues were analyzed.ResultsIn vitro HSCs study showed significant higher [3H]proline uptake (23007.9 ± 5089.2 vs. 1075.4 ± 119.3 CPM/mg, p < 0.001) in HSCs isolated from AALF rats than controls and so was collagen type 1 production (24.3 ± 5.8 vs. 3.0 ± 0.62 mg/ml, p < 0.001) in HSCs culture medium. Highly positive correlation between [3H]proline uptake and collagen type 1 by HSCs of AALF rats was found (r value = 0.92, p < 0.01). Ex vivo liver tissue study showed no significant difference in collagen type 1 levels between AALF rats (14.83 ± 5.35 mg/g) and AALF mice (12.91 ± 3.62 mg/g, p > 0.05), so was proline transporter expression between AALF rats (7.76 ± 1.92-fold) and AALF mice (6.80 ± 0.97-fold). Unlabeled fluoro-proline induced generation of liver tissue collagen type 1 and [3H]proline uptake were specifically blocked by transporter inhibitor. In vivo [18F]proline micro PET/CT imaging showed higher SUVmax in liver (4.90 ± 0.91 vs. 1.63 ± 0.38, p < 0.01), higher normalized liver/brain ratio (12.54 ± 0.72 vs. 2.33 ± 0.41, p < 0.01), and higher normalized liver/thigh ratio (6.03 ± 0.78 vs. 1.09 ± 0.09, p < 0.01) in AALF mice than controls, which are all positively correlated with fluoro-proline-induced levels of collagen in liver tissue (r value ≥ 0.93, p < 0.01) in AALF mice, but not correlated with existing liver collagen. Liver histology showed increased collagen in the liver of AALF mice. Blood serum ALT and AST levels were remarkably higher in AALF mice than in controls, but there is no significant difference in blood fibrotic parameters HA, A2M, TGFβ1, and MMP1.Conclusions[18F]proline micro PET/CT might be useful to visualize collagenogenesis in activated HSC of experimental AALF but fails to quantify existing liver collagen in AALF mice. [18F]proline has the potential sensitivity to assess the activity and severity of liver fibrosis.

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“…Liver histology is the classic diagnostic method to estimate the progression of liver fibrosis which relied on professional pathologists, because it is time-consuming, invasive, difficult to operate, and expensive, and poses a variety of complications, the application of liver biopsy is limited in clinic ( McGill et al, 1990 ). Several noninvasive methods have been reported that could be used in evaluating the severity of liver fibrosis ( Cao et al, 2020 ; Loomba and Adams, 2020 ). One of the most common noninvasive scoring systems is the aspartate aminotransferase-to-platelet ratio index (APRI) and the other is fibrosis index based on the four factors (FIB-4), both of them have been indicated to predict severe liver fibrosis or liver cirrhosis ( Wai et al, 2003 ; Vallet-Pichard et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

LECT2, A Novel and Direct Biomarker of Liver Fibrosis in Patients With CHB

et al. 2021

Front. Mol. Biosci.

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Chronic hepatitis B (CHB) patients with severe liver fibrosis would be more likely to progress to a poorer prognosis. Treatment is considered once the liver fibrosis reaches significant liver fibrosis (≥S2). Leukocyte cell-derived chemotaxin-2 (LECT2) has been shown to contribute to liver fibrosis progression. No research has focused on the role of LECT2 in liver fibrosis in CHB patients. This study enrolled 227 CHB patients and divided them into the training group (n = 147) and validation group (n = 80), respectively. The expression of LECT2 in serum, protein and mRNA of the human liver tissues was detected to analyze the possible associations between LECT2 and liver fibrosis. A receiver operating characteristic curve (ROC) was used to estimate the efficacy of LECT2 for predicting liver fibrosis. The data showed that there was a positive relationship between LECT2 and the progression of liver fibrosis. In the training group, LECT2 was demonstrated to have better effectiveness than APRI and FIB-4. The AUC was 0.861, 0.698, and 0.734 for significant liver fibrosis, and 0.855, 0.769, and 0.752 for advanced liver fibrosis. Besides, the efficacy of LECT2 in different statuses of patients with CHB was examined and the effectiveness of LECT2 had also been confirmed in the validation group. All the results confirmed that LECT2 could act as a perfect predictor and thus offers a novel and direct biomarker to estimate liver fibrosis more accurately.

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cis-4-[18F]fluoro-L-proline Molecular Imaging Experimental Liver Fibrosis

Cited by 8 publications

References 49 publications

Steam Explosion-Assisted Extraction of Protein from Fish Backbones and Effect of Enzymatic Hydrolysis on the Extracts

Steam Explosion-Assisted Extraction of Protein from Fish Backbones and Effect of Enzymatic Hydrolysis on the Extracts

Cis-4-[18F]fluoro-L-proline PET/CT molecular imaging quantifying liver collagenogenesis: No existing fibrotic deposition in experimental advanced-stage alcoholic liver fibrosis

LECT2, A Novel and Direct Biomarker of Liver Fibrosis in Patients With CHB

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