Cre/lox-assisted non-invasive in vivo tracking of specific cell populations by positron emission tomography

Thunemann, Martin; Schörg, Barbara F.; Feil, Susanne; Lin, Yuan; Voelkl, Jakob; Golla, Matthias; Vachaviolos, Angelos; Kohlhofer, Ursula; Quintanilla-Martı́nez, Leticia; Olbrich, Marcus; Ehrlichmann, Walter; Reischl, Gerald; Griessinger, Christoph M.; Langer, Harald F.; Gawaz, Meinrad; Läng, Florian; Schäfers, Michael; Kneilling, Manfred; Pichler, Bernd J.; Feil, Robert

doi:10.1038/s41467-017-00482-y

Cited by 37 publications

(31 citation statements)

References 54 publications

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“…Smal l-animal in vivo imaging has revealed its striking potential as a research tool to noninvasively study the onset and progression of multiple diseases (1,2), to evaluate novel PET tracers (3,4), or to contribute to drug development (1,5,6). It further enables in vivo therapy monitoring and bridges the gap of straightforward translation to clinical applications (1,3,7,8).…”

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confidence: 99%

Reproducibility and Comparability of Preclinical PET Imaging Data: A Multicenter Small-Animal PET Study

et al. 2019

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The standardization of preclinical imaging is a key factor to ensure the reliability, reproducibility, validity, and translatability of preclinical data. Preclinical standardization has been slowly progressing in recent years and has mainly been performed within a single institution, whereas little has been done in regards to multicenter standardization between facilities. This study aimed to investigate the comparability among preclinical imaging facilities in terms of PET data acquisition and analysis. In the first step, basic PET scans were obtained in 4 different preclinical imaging facilities to compare their standard imaging protocol for 18 F-FDG. In the second step, the influence of the personnel performing the experiments and the experimental equipment used in the experiment were compared. In the third step, the influence of the image analysis on the reproducibility and comparability of the acquired data was determined. Distinct differences in the uptake behavior of the 4 standard imaging protocols were determined for the investigated organs (brain, left ventricle, liver, and muscle) due to different animal handling procedures before and during the scans (e.g., fasting vs. nonfasting, glucose levels, temperature regulation vs. constant temperature warming). Significant differences in the uptake behavior in the brain were detected when the same imaging protocol was used but executed by different personnel and using different experimental animal handling equipment. An influence of the person analyzing the data was detected for most of the organs, when the volumes of interest were manually drawn by the investigators. Coregistration of the PET to an MR image and drawing the volume of interest based on anatomic information yielded reproducible results among investigators. It has been demonstrated that there is a huge demand for standardization among multiple institutions.

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confidence: 99%

Reproducibility and Comparability of Preclinical PET Imaging Data: A Multicenter Small-Animal PET Study

et al. 2019

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“…Traditional methods for detecting the distribution and therapeutic effects of targeted therapeutic genes in tumor tissues are often based on invasive methods. However, molecular imaging can observe the effects of gene therapy on liver cancer at an early stage and continuously in vivo, and it plays an important role in revealing the mechanism-of-action of targeted drugs [14,15]. Therefore, it is very important to study a method for non-invasive monitoring of the dynamic distribution and curative effect of the targeted therapeutic gene in vivo.…”

Section: Ivyspringmentioning

confidence: 99%

“…It introduces an exogenous gene (reporter gene) into cells, and the reporter gene expresses specific products such as enzymes, receptor proteins, or transporters. The technique of imaging analysis is then performed using a substrate of the radionuclide-labeled gene expression product [14,18]. Molecular imaging technology of reporter genes can non-invasively, repeatedly, and quantitatively observe gene expression in living tissues, which can be used as a useful tool to detect gene transfer and distribution in vivo [17,19], thus showing great potential for monitoring gene therapy.…”

Section: Ivyspringmentioning

confidence: 99%

“…Molecular imaging technology of reporter genes can non-invasively, repeatedly, and quantitatively observe gene expression in living tissues, which can be used as a useful tool to detect gene transfer and distribution in vivo [17,19], thus showing great potential for monitoring gene therapy. Herpes simplex virus type 1 thymidine kinase (HSV1-TK) is one of the most common and sensitive reporter genes [14]. Furthermore, 9-[4-[ 18 F] fluoro-3-(hydroxymethyl) butyl] guanine ( 18 F-FHBG) is the most studied positron emission tomography (PET) imaging probe that can be combined with the HSV1-TK expression product specifically.…”

Section: Ivyspringmentioning

confidence: 99%

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Visualization of gene therapy with a liver cancer-targeted adeno-associated virus 3 vector

Liu¹,

Huang²,

Gao³

et al. 2020

J. Cancer

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Background: To evaluate the feasibility of a self-complementing recombinant adeno-associated virus 3 (scrAAV3) vector targeting liver cancer and non-invasively monitor gene therapy of liver cancer. Materials and methods: An scrAAV3-HSV1-TK-kallistatin (ATK) gene drug was constructed, which contained the herpes virus thymidine kinase (HSV1-TK) reporter gene and human endogenous angiogenesis inhibitor (kallistatin) gene for non-invasive imaging of gene expression. Subcutaneous xenografted tumors of hepatoma in nude mice were generated for positron emission tomography/computed tomography (PET/CT) imaging. The ATK group was injected with the ATK gene through the tail vein, and an imaging agent was injected 2 weeks later. PET/CT imaging was performed at 1 hour after injection of the imaging agent. The control group was injected with phosphate-buffered saline at the same volume as the ATK gene drug. HE staining is used for pathological observation of tumor sections. HSV1-TK and kallistatin expression was identified by immunofluorescence, real-time quantitative PCR, and western blotting. Results: Radioactivity on PET/CT images was significantly higher in the ATK group compared with the control group. 18F-FHBG uptake values of left forelegs in ATK and control groups were 0.591±0.151% and 0.017 ± 0.011% ID/g (n=5), respectively (P<0.05). After injection of the ATK gene drug, mRNA and protein expression of HSV1-TK and kallistatin in subcutaneous xenograft tumors was detected successfully. In vitro analysis demonstrated significant differences in the expression of HSV1-TK and kallistatin between ATK and control groups (P<0.05). Conclusions: The scrAAV3 vector has a strong liver cancer-targeting ability, and the ATK gene drug can be used for targeted and non-invasive monitoring of liver cancer gene therapy.

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“…Direct cell labelling in molecular in vivo imaging can be done by various compounds including radioactive, paramagnetic or fluorescent agents. 63 For MRI (magnetic resonance imaging), the nanoparticles consist of superparamagnetic iron oxide (SPIO) nanoparticles, perfluorocarbon nanoparticles, gadolinium-filled microcapsules and liposomes. 61,64 Direct cell labelling for nuclear imaging will be implemented with radioisotopes such as 111 Indium ( 111 In…”

Section: Direct Cell Labellingmentioning

confidence: 99%

Optical fluorescence imaging with shortwave infrared light emitter nanomaterials for in vivo cell tracking in regenerative medicine

Fath‐Bayati

Vasei

Sharif‐Paghaleh

2019

J Cellular Molecular Medi

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In vivo tracking and monitoring of adoptive cell transfer has a distinct importance in cell‐based therapy. There are many imaging modalities for in vivo monitoring of biodistribution, viability and effectiveness of transferred cells. Some of these procedures are not applicable in the human body because of low sensitivity and high possibility of tissue damages. Shortwave infrared region (SWIR) imaging is a relatively new technique by which deep biological tissues can be potentially visualized with high resolution at cellular level. Indeed, scanning of the electromagnetic spectrum (beyond 1000 nm) of SWIR has a great potential to increase sensitivity and resolution of in vivo imaging for various human tissues. In this review, molecular imaging modalities used for monitoring of biodistribution and fate of administered cells with focusing on the application of non‐invasive optical imaging at shortwave infrared region are discussed in detail.

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Cre/lox-assisted non-invasive in vivo tracking of specific cell populations by positron emission tomography

Cited by 37 publications

References 54 publications

Reproducibility and Comparability of Preclinical PET Imaging Data: A Multicenter Small-Animal PET Study

Reproducibility and Comparability of Preclinical PET Imaging Data: A Multicenter Small-Animal PET Study

Visualization of gene therapy with a liver cancer-targeted adeno-associated virus 3 vector

Optical fluorescence imaging with shortwave infrared light emitter nanomaterials for in vivo cell tracking in regenerative medicine

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