Ferritin heavy chain as a molecular imaging reporter gene in glioma xenografts

Cheng, Sen; Mi, Ruifang; Xu, Yu; Jin, Guishan; Zhang, Junwen; Zhou, Yiqiang; Chen, Zhengguang; Liu, Fusheng

doi:10.1007/s00432-017-2356-z

Cited by 10 publications

(7 citation statements)

References 36 publications

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“…The cells were centrifugated once again and finally suspending in 10 µL PBS in EP tubes and filled with 1% un-solidified agarose solution in each tube. 21 , 41 , 42 T2*-weighted imaging (T2*WI), T2WI, and T2 values were acquired using T2 fast spin-echo and ESWAN sequences by a 3.0-T MR (GE Discovery MR750, USA). FSE sequence: repetition time (TR) = 3070.0 ms, echo time (TE) = 96.6 ms, and slice thickness = 1.0 mm; ESWAN sequence: TR = 52.3 ms, TE = 6.5–30.2 ms, and slice thickness = 1.0 mm.…”

Section: Methodsmentioning

confidence: 99%

<p>Dual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma</p>

Zhou

Gao

et al. 2020

IJN

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Propose: The early diagnosis of hepatocellular carcinoma (HCC) with ferritin heavy chain (Fth) modified by alpha-fetoprotein (AFP) promoter has been studied. However, no study has focused on the considerable upregulation and specific targeting effects of transferrin receptors (TfR) caused by the transfection of plasmids encoded with the AFP promoter. Thus, the objective of our study was to investigate whether the transfection of Fth gene modified with AFP promoter (AFP@Fth) could be used for early diagnosis and enhanced treatment of HCC. Methods: The AFP@Fth plasmid was transfected into AFP positive cells. The expression of intracellular Ferritin was verified by Western blot, and the upregulation of TfR was confirmed by immunofluorescence and flow cytometry analysis. Cellular iron accumulation resulting in decreased imaging signals was examined by magnetic resonance imagining. Doxorubicin liposome modified with transferrin (Tf-LPD) was prepared to investigate the efficiency of the subsequent treatment after transfection. The enhanced drug distribution and effects were investigated both in vitro and in vivo. Results: Both Ferritin and TfR were overexpressed after transfection. The transfected cells showed higher intracellular iron accumulation and resulted in a lower MR T2-weighted imaging (T2WI) intensity, suggesting that the transfection of AFP@Fth could be a potential strategy for early diagnosis of liver cancer. The following treatment efficacy was revealed by Tf-LPD. As compared with un-transfected cells, transfected cells exhibited higher uptake of transferrin-modified liposomes (Tf-LP), which was due to the specific interaction between Tf and TfR overexpressed on the transfected cells. This is also the reason why Tf-LPD showed better in vitro and in vivo anticancer ability than doxorubicin loaded liposome (LPD). These results suggested that transfection of AFP@Fth could result in enhanced therapy of liver cancer. Conclusion: Transfection of AFP@Fth could be used for early diagnosis and for enhanced treatment of live cancers.

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Section: Methodsmentioning

confidence: 99%

<p>Dual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma</p>

Zhou

Gao

et al. 2020

IJN

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“…The herpes simplex virus type-1(HSV1-tk) and its mutant HSV1-sr39tk from thymidine kinase (TK) are enzyme-based reporter genes for PET imaging with 124 I-FIAU (2-fluoro-2-deoxy-1-β-D-arabinofuranosyl-5-iodouracil) or 18 F-FHBG (9-(4- 18 F-Fluoro-3-[hydroxymethyl]butyl)guanine) 49 . Human ferritin heavy chain (hFTH) is a novel gene reporter in magnetic resonance imaging 50 . The overexpression of transferrin receptors (TfR) induces a significant reduction in T2-weighted signal intensity on MRI 51 .…”

Section: Direct Imaging Strategy Vs Reporter Genmentioning

confidence: 99%

Multimodality reporter gene imaging: Construction strategies and application

Li¹,

Wang²,

Liu³

et al. 2018

Theranostics

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Molecular imaging has played an important role in the noninvasive exploration of multiple biological processes. Reporter gene imaging is a key part of molecular imaging. By combining with a reporter probe, a reporter protein can induce the accumulation of specific signals that are detectable by an imaging device to provide indirect information of reporter gene expression in living subjects. There are many types of reporter genes and each corresponding imaging technique has its own advantages and drawbacks. Fused reporter genes or single reporter genes with products detectable by multiple imaging modalities can compensate for the disadvantages and potentiate the advantages of each modality. Reporter gene multimodality imaging could be applied to trace implanted cells, monitor gene therapy, assess endogenous molecular events, screen drugs, etc. Although several types of multimodality imaging apparatus and multimodality reporter genes are available, more sophisticated detectors and multimodality reporter gene systems are needed.

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“…Modern molecular imaging can supply early tumor diagnosis, which used novel reporter genes for MRI gene expression, including ferritin, transferrin receptor, β-galactosidase, and tyrosinase [14,15,17]. As an endogenous contrast agent, ferritin reporter gene shows no cellular toxicity and can persistently produce a reduction of the signal intensity in MRI without fading over time comparing with exogenous contrast agents [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Enhanced transferrin modified targeting delivery system via AFP promoter MR imaging reporter gene transfection

Zhou

Gao

et al. 2020

Preprint

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Background: Effective treatment and early diagnosis is essential for patients with hepatocellular carcinoma. Nowadays, there is an increasing interest in the utilization of AFP/Fth as an endogenous contrast agent for the early diagnosis of liver cancers. The transfection of AFP/Fth also leads to a considerable upregulation of transferrin receptors (TfR), which might be a potential target for an enhanced delivery of nanomedicines. However, there is no information regarding the utilization of overexpressed TfR for the treatment of liver cancers. Thus, the objective of our study was to investigate whether the transfection of AFP/Fth could be used for the early diagnosis, but also for an enhanced treatment of live cancers. Results: It was found that both of ferritin and TfR were upregulated after the transfection of AFP/Fth plasmid. The transfected cells showed a higher uptake of ferric ion than the un-transfected ones, resulting in a lower T2WI intensity. This result was due to the upregulation of ferritin in transfected cells, suggesting that transfection of AFP/Fth plasmid could be a potential strategy for early diagnosis of liver cancer. As compared with the un-transfected cells, the transfected cells showed a higher uptake of transferrin-modified liposomes, which was due to the specific interaction between transferrin with TfR overexpressed on the transfected cells. This is also the reason why the transferrin modified doxorubicin loaded liposomes (Tf-LP/DOX) showed better in vitro and in vivo anticancer ability than the LP/DOX. This results also suggested that transfection of AFP/Fth could result in an enhanced therapy of liver cancer. Conclusions: Transfection of AFP/Fth could be used for the early diagnosis, but also for an enhanced treatment of live cancers.

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Ferritin heavy chain as a molecular imaging reporter gene in glioma xenografts

Abstract: Our study illustrated that hFTH generated cellular MR imaging contrast efficiently in glioma via regulating the expression of transferritin receptor. This might be a useful reporter gene in cell tracking and MR molecular imaging for glioma diagnosis, gene therapy and tumor metastasis.

Cited by 10 publications

References 36 publications

<p>Dual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma</p>

<p>Dual-Effect of Magnetic Resonance Imaging Reporter Gene in Diagnosis and Treatment of Hepatocellular Carcinoma</p>

Multimodality reporter gene imaging: Construction strategies and application

Enhanced transferrin modified targeting delivery system via AFP promoter MR imaging reporter gene transfection

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