Molecular imaging of gene therapy for cancer

Shah, Khalid; Jacobs, Alice K.; Breakefield, Xandra O.; Weissleder, Ralph

doi:10.1038/sj.gt.3302278

Cited by 178 publications

(106 citation statements)

References 79 publications

(89 reference statements)

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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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“…26 The imaging of hNIS-expressing tissues is particularly versatile since hNIS can promote cellular uptake of different radioisotopes 123 I (SPECT), 124 I (PET), 99m Tc (SPECT), 131 I (scintigraphic imaging). 19,[25][26][27][28] In the present study, we have generated two replication-competent adenoviruses (AdIP1 and AdAM6) encoding the hNIS cDNA. AdIP1 is a 'wild-type' virus based on the Ad-5 serotype in which the only modification is the replacement of the gp19k gene in the E3 region by the hNIS cDNA.…”

Section: Introductionmentioning

confidence: 99%

SPECT/CT imaging of oncolytic adenovirus propagation in tumours in vivo using the Na/I symporter as a reporter gene

et al. 2007

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Oncolytic adenoviruses have shown some promise in cancer gene therapy. However, their efficacy in clinical trials is often limited, and additional therapeutic interventions have been proposed to increase their efficacies. In this context, molecular imaging of viral spread in tumours could provide unique information to rationalize the timing of these combinations. Here, we use the human sodium iodide symporter (hNIS) as a reporter gene in wild-type and replication-selective adenoviruses. By design, hNIS cDNA is positioned in the E3 region in a wild-type adenovirus type 5 (AdIP1) and in an adenovirus in which a promoter from the human telomerase gene (RNA component) drives E1 expression (AdAM6). Viruses show functional hNIS expression and replication in vitro and kinetics of spread of the different viruses in tumour xenografts are visualized in vivo using a small animal nano-SPECT/CT camera. The time required to reach maximal spread is 48 h for AdIP1 and 72 h for AdAM6 suggesting that genetic engineering of adenoviruses can affect their kinetics of spread in tumours. Considering that this methodology is potentially clinically applicable, we conclude that hNIS-mediated imaging of viral spread in tumours may be an important tool for combined anticancer therapies involving replicating adenoviruses.

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“…[37][38][39] BLI has been used to monitor tumor cell growth and regression 40,41 to visualize the kinetics of tumor cell clearance by chemotherapeutics 42 and to track gene expression. 43 …”

Section: Bioluminescence Imagingmentioning

confidence: 99%

Molecular optical imaging: Applications leading to the development of present day therapeutics

Shah

Weissleder

2005

Neurotherapeutics

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Summary:A number of advances in the molecular imaging field have led to the sensing of specific molecular targets and pathways in living animals. In the optical imaging field, these include the designing of biocompatible near-infrared fluorochromes, development of targeted and activatable "smart" imaging probes, and engineering of activatable fluorescent and bioluminescent proteins. The current advances in molecular optical imaging will help in early disease diagnoses, functioning of a number of pathways and finally help speed drug discovery. In this review, we will describe the near infrared fluorescent and bioluminescence imaging modalities and how these techniques have been employed in current research. Furthermore, we will also shed some light on the use of these imaging modalities in neurotherapeutics, for example imaging different parameters of vector-mediated gene expression in glioma tumors and stem cell tracking in vivo.

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Molecular imaging of gene therapy for cancer

Cited by 178 publications

References 79 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

SPECT/CT imaging of oncolytic adenovirus propagation in tumours in vivo using the Na/I symporter as a reporter gene

Molecular optical imaging: Applications leading to the development of present day therapeutics

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