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MR molecular imaging of HCC employing a regulated ferritin gene carried by a modified polycation vector.

ABSTRACT: Purpose: Early diagnosis is essential for reducing liver cancer mortality, and molecular diagnosis by magnetic resonance imaging (MRI) is an emerging and promising technology. The chief aim of the present work is to use the ferritin gene, modified by the alpha-fetoprotein (AFP) promoter, carried by a highly safe vector, to produce signal contrast on T2-weighted MR imaging as an endogenous contrast agent, and to provide a highly specific target for subsequent therapy. Methods: Polyethyleneimine-?-cyclodextrin (PEI-?-CD, PC) was synthesized as a novel vector. The optimal nitrogen/phosphorus ratio (N/P) of the PC/plasmid DNA complex was determined by gel retardation, biophysical properties and transmission electron microscopy morphological analysis. The transfection efficiency was observed under a fluorescence microscope and analyzed by flow cytometry. Cellular iron accumulation caused by ferritin overexpression was verified by Prussian blue staining, and the resulting contrast imaging effect was examined by MRI. Results: The modified cationic polymer PC was much safer than high molecular weight PEI, and could condense plasmid DNA at an N/P ratio of 50 with suitable biophysical properties and a high transfection efficiency. Overexpression of ferritin enriched intracellular iron. The short-term iron imbalance initiated by AFP promoter regulation only occurred in hepatoma cells, resulting in signal contrast on MRI. The specific target TfR was also upregulated during this process. Conclusion: These results illustrate that the regulated ferritin gene carried by PC can be used as an endogenous contrast agent for MRI detection of hepatocellular carcinoma (HCC). This molecular imaging technique may promote safer early diagnosis of HCC, and provide a more highly specific target for future chemotherapy drugs.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC6504634 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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MR molecular imaging of HCC employing a regulated ferritin gene carried by a modified polycation vector.

Zhang Qian Q Lu Yuanfei Y Xu Xiaoling X Li Shujuan S Du Yongzhong Y Yu Risheng R

International journal of nanomedicine 20190502

<b>Purpose:</b> Early diagnosis is essential for reducing liver cancer mortality, and molecular diagnosis by magnetic resonance imaging (MRI) is an emerging and promising technology. The chief aim of the present work is to use the ferritin gene, modified by the alpha-fetoprotein (AFP) promoter, carried by a highly safe vector, to produce signal contrast on T2-weighted MR imaging as an endogenous contrast agent, and to provide a highly specific target for subsequent therapy. <b>Methods:</b> Polye ...[more]

PMID: 31118631

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Project description:PurposeTo quantitatively monitor the dynamic perivascular recruitment of ferritin heavy chain (FHC)-overexpressing fibroblasts to ovarian carcinoma xenografts by using R2 mapping and biexponential magnetic resonance (MR) relaxometry.Materials and methodsIn vivo studies of female mice were approved by the institutional animal care and use committee. In vitro analysis included MR-based R2 relaxation measurements of monkey kidney cell line (CV1) fibroblasts that overexpress FHC, followed by inductively coupled plasma mass spectrometry to assess cellular iron content. For in vivo analysis, CV1-FHC fibroblasts were either mixed with fluorescent human ovarian carcinoma cells before subcutaneous implantation (coinjection) or injected intraperitoneally 4 days after the cancer cells were injected (remote recruitment). Dynamic changes in tumor R2 were used to derive CV1-FHC cell fraction in both models. In coinjection tumors, dynamic contrast material-enhanced MR imaging was used to measure tumor fractional blood volume. Whole-body fluorescence imaging and immunohistochemical staining were performed to validate MR results. One-way repeated measures analysis of variance was used to assess MR and fluorescence imaging results and tumor volume, and one-way analysis of variance was used to assess spectrometric results, fractional blood volume, and immunohistochemical evaluation.ResultsCV1-FHC fibroblasts (vs CV1 fibroblasts) showed enhanced iron uptake (1.8 mmol ± 0.5 × 10(-8) vs 0.9 mmol ± 0.5 × 10(-8); P < .05), retention (1.6 mmol ± 0.5 × 10(-8) vs 0.5 mmol ± 0.5 × 10(-8), P < .05), and cell density-dependent R2 contrast. R2 mapping in vivo revealed preferential recruitment of CV1-FHC cells to the tumor rim in both models. Measurement of fractional blood volume was similar in all tumors (2.6 AU ± 0.5 × 10(-3) for CV1, 2.3 AU ± 0.3 × 10(-3) for CV1-FHC, 2.9 ± 0.3 × 10(-3) for CV1-FHC-ferric citrate). Dynamic changes in CV1-FHC cell fraction determined at MR relaxometry in both models were confirmed at immunohistochemical analysis.ConclusionFHC overexpression, when combined with R2 mapping and MR relaxometry, enabled in vivo detection of the dynamic recruitment of exogenously administered fibroblasts to the vasculature of solid tumors.

Project description:ObjectiveTo compare the reliability of different methods for measuring fat content of pancreas by MR modified Dixon(mDixon) Sequence and accurately evaluate pancreatic fat in as simple a way as possible.MethodsThis is a retrospective study, 64 patients were included in this study who underwent abdominal MR scan that contained the mDixon sequence from June 2019 to May 2020(Included 7 patients with type 2 diabetes and 4 patients with impaired glucose tolerance (IGT), they were admitted to hospital through the obesity clinic set up by endocrine department, all of them were initially diagnosed and untreated). All of the 64 patients were scanned in 3.0T MR (Philips Ingenia II) due to their condition, 10-34 slice pancreas images were obtained, which were different from each other. Three different methods of measurement were employed by two observers using Philips Intellispace Portal software: (1) All images (whole-pancreas) measurement, the whole-pancreatic fat fraction (wPFF) was calculated by software. (2) Interval slices measurement, that is half-pancreatic slices fat fraction (hPFF) measured in the same way, fat fraction obtained by the interlayer assay was calculated. (3) As usual, the fat content of pancreatic head, body and tail fat was measured respectively, and in order to improve credibility, we also measured head、 body and tail in every layer, and its average value was taken. The elapsed time of the above different measurement methods was recorded. Intra-group correlation coefficient (ICC) was used to analyze the consistency of the measured data within and between observers. T-tests and Friedman tests were applied to compare the difference of measured values among groups.ResultsNo matter in normal person or diabetic or IGT, hPFF has shown good stability (ICChPFF = 0.988), and there was no significant difference compared with wPFF. But the average fat percentage composition of head, body and tail were significantly different from wPFF and hPFF (P < 0.01). At the same time, compared with normal person, pancreatic fat content in IGT and diabetic patients showed progressive significance(P<0.05).ConclusionThe distribution of pancreatic fat is not uniform, the method of measuring half pancreas by interlayer data collection can reflect the fat content of the entire pancreas, this suggests that measuring 50% of the pancreas is sufficient, this method effectively saves time and effort without affecting the results, which may have a better clinical application prospect.

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MR molecular imaging of HCC employing a regulated ferritin gene carried by a modified polycation vector.

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MR molecular imaging of HCC employing a regulated ferritin gene carried by a modified polycation vector.

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