Gene Therapy Progress and Prospects: Noninvasive imaging of gene therapy in living subjects

Min, Jung Joon; Gambhir, SS

doi:10.1038/sj.gt.3302191

Cited by 88 publications

(46 citation statements)

References 78 publications

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“…Measurements can be attained by different techniques, such as scintigraphy, magnetic resonance, ultrasound, bioluminescence or positron emission tomography (PET) imaging, with specific potential for different clinical applications. [5][6][7] In most instances, reporter genes whose function provides signal must be engineered to have behaviour similar to that of the therapeutic gene. Robust quantitative parameters allowing comparative studies would be very helpful.…”

Section: Introductionmentioning

confidence: 99%

PET imaging of thymidine kinase gene expression in the liver of non-human primates following systemic delivery of an adenoviral vector

et al. 2008

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and 4 CIBER en enfermedades hepáticas y digestivas, SpainNon-invasive in vivo imaging of transgene expression is currently providing very important means to optimize gene therapy regimes. Results in non-human primates are considered the most predictive models for the outcome in patients. In this study, we have documented that tumour and primary cell lines from human and non-human primates are comparably gene-transduced in vitro by serotype 5 adenovirus expressing HSV1-thymidine kinase. Transgene expression can be quantified in human and monkey cultured cells by positron emission tomography (PET) imaging when transduced cells are incubated with a fluoride-18 labelled penciclovir analogue. In our hands, PET images of cell cultures estimate the number of transduced cells rather than intensity of transgene expression once a threshold of TK per cell is reached. Interestingly, in vivo systemic administration of a clinical grade recombinant adenovirus expressing TK into macaques gives rise to an intense retention of the radiotracer in the liver parenchyma, providing an experimental system to visualize transgene expression that ought to be similar in human and macaques. Such imaging methodology might contribute to improve strategies based on adenoviral vectors.

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Section: Introductionmentioning

confidence: 99%

PET imaging of thymidine kinase gene expression in the liver of non-human primates following systemic delivery of an adenoviral vector

et al. 2008

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“…Imaging reporter gene expression with positron emission tomography (PET) is a growing field with many types of reporter genes/reporter probes under development and validation [1,2].…”

Section: Introductionmentioning

confidence: 99%

Semiautomated Radiosynthesis and Biological Evaluation of [18F]FEAU: A Novel PET Imaging Agent for HSV1-tk/sr39tk Reporter Gene Expression

et al. 2007

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2′-Deoxy-2′-[ 18 F]fluoro-5-ethyl-1-β-D-arabinofuranosyluracil ([ 18 F]FEAU) is a promisingradiolabeled nucleoside designed to monitor Herpes Simplex Virus Type 1 thymidine kinase (HSV1-tk) reporter gene expression with positron emission tomography (PET). However, the challenging radiosynthesis creates problems for being able to provide [ 18 F]FEAU routinely. We have developed a routine method using a commercial GE TRACERlab FX-FN radiosynthesis module with customized equipment to provide [ 18 F]FEAU. All radiochemical yields are decay corrected to end-of-bombardment and reported as means±SD. Radiofluorination (33±8%; n=4), bromination (85±8%; n=4), coupling reaction (83±6%; n=4), base hydrolysis steps, and subsequent high-performance liquid chromatography purification afforded purified [ 18 F]FEAU β-anomer in 5±1% overall yield (n=3 runs) after ∼5.5 h and a β/α-anomer ratio of 7.4. Radiochemical/chemical purities and specific activity exceeded 99% and 1.

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“…Several molecular imaging technologies have been used to try to monitor transgene expression for gene therapy, including MRI, optical imaging, and radionuclide imaging techniques such as PET and SPECT [10][11][12][13][14]. Reporter genes with optical signatures (e.g., fluorescence and bioluminescence) are low-cost alternatives for real-time analysis of gene expression in small-animal models.…”

Section: Molecular Imaging Modalities and Imaging Reporter Genesmentioning

confidence: 99%

Molecular Imaging of Biological Gene Delivery Vehicles for Targeted Cancer Therapy: Beyond Viral Vectors

Min

Nguyen

Gambhir

2010

Nucl Med Mol Imaging

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Cancer persists as one of the most devastating diseases in the world. Problems including metastasis and tumor resistance to chemotherapy and radiotherapy have seriously limited the therapeutic effects of present clinical treatments. To overcome these limitations, cancer gene therapy has been developed over the last two decades for a broad spectrum of applications, from gene replacement and knockdown to vaccination, each with different requirements for gene delivery. So far, a number of genes and delivery vectors have been investigated, and significant progress has been made with several gene therapy modalities in clinical trials. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications. However, both have limitations and risks that restrict gene therapy applications, including the complexity of production, limited packaging capacity, and unfavorable immunological features. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents such as bacteria, bacteriophages, and bacteria-like particles. Recently, many molecular imaging techniques for safe, repeated, and high-resolution in vivo imaging of gene expression have been employed to assess vector-mediated gene expression in living subjects. In this review, molecular imaging techniques for monitoring biological gene delivery vehicles are described, and the specific use of these methods at different steps is illustrated. Linking molecular imaging to gene therapy will eventually help to develop novel gene delivery vehicles for preclinical study and support the development of future human applications.

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Gene Therapy Progress and Prospects: Noninvasive imaging of gene therapy in living subjects

Cited by 88 publications

References 78 publications

PET imaging of thymidine kinase gene expression in the liver of non-human primates following systemic delivery of an adenoviral vector

PET imaging of thymidine kinase gene expression in the liver of non-human primates following systemic delivery of an adenoviral vector

Semiautomated Radiosynthesis and Biological Evaluation of [18F]FEAU: A Novel PET Imaging Agent for HSV1-tk/sr39tk Reporter Gene Expression

Molecular Imaging of Biological Gene Delivery Vehicles for Targeted Cancer Therapy: Beyond Viral Vectors

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