Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals

MacLaren, Duncan C.; Gambhir, Sanjiv S.; Satyamurthy, Nagichettiar; Barrio, Jorge R.; Sharfstein, Susan T.; Toyokuni, Tatsushi; Wu, Lily; Berk, Arnold; Cherry, Simon R.; Phelps, Michael E.; Herschman, Harvey R.

doi:10.1038/sj.gt.3300877

Cited by 332 publications

(166 citation statements)

References 36 publications

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“…Optical candidates include luciferase, 32 GFP, 33 protease activatable fluoroscopic dyes, 34 while MR techniques include engineered internalizing receptors 35 or tyrosinase. 36 PET agents include reporter probes such as FESP (an agonist for dopamine receptors) 37 and 18-FIAU or 18-F gancyclovir/pencyclovir for imaging thymidine kinase. 38,39 The ideal gene therapy paradigm for brain tumors has yet to be evolved, but may consist of a combination of intratumor injection and intra-arterial administration of vectors bearing therapeutic transgenes.…”

Section: Discussionmentioning

confidence: 99%

Quantitation of HSV mass distribution in a rodent brain tumor model

Schellingerhout¹,

Rainov

Breakefield

et al. 2000

Gene Ther

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A number of different viral vectors have been used for gene therapy of tumors, with many more under construction, ultimately designed to improve tumor targeting and transduction efficiency. It has become apparent that insufficient viral delivery can be a key limitation to treatment efficacy. We have studied the in vivo mass distribution of a herpes simplex virus type 1 (HSV) vector, hrR3, by radiolabeling it with 111 In-oxine. The virus was administered to intracerebral 9L glioma bearing Fisher (F-344) rats by intracarotid and intratumoral injection. The blood half-life of the virus was 1 min (fast component, 10% contribution) and 180 min (slow component, 90% contribution). Approximately 20% of activity had been excreted by 24 h. With intracarotid injection, the total amount of virus that accumulated in tumor was 0.10 ± 0.07% of the injected dose (ID)/g at 1 h and 0.19 ± 0.01% ID/g at 24 h. By comparison, co-injection of RMP-7,

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Section: Discussionmentioning

confidence: 99%

Quantitation of HSV mass distribution in a rodent brain tumor model

Schellingerhout¹,

Rainov

Breakefield

et al. 2000

Gene Ther

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“…Currently, the somatostatin receptor gene 5,6 the HSV1-tk gene [9][10][11][12][13][14][15] and the D2R gene 8,20 have been the subject of the most extensive analyses for in vivo reporter gene development, using positron-emitting, radiolabeled probe detection systems.…”

Section: Discussionmentioning

confidence: 99%

“…MicroPET (a small animal positron emission tomograph (PET) scanner 7 ) can be used, following systemic FESP injection, to image hepatic D2R reporter gene expression in mice injected with an adenovirus in which the D2R is driven by a cytomegalovirus promoter. 8 A second approach to in vivo imaging uses enzymes as reporter genes and radiolabeled substrates as reporter probes that are converted to sequestered forms by the activities of the reporter enzymes. The most popular enzyme reporter gene is herpes simplex virus 1 thymidine kinase (HSV1-tk).…”

Section: Introductionmentioning

confidence: 99%

Monitoring adenoviral DNA delivery, using a mutant herpes simplex virus type 1 thymidine kinase gene as a PET reporter gene

et al. 2002

Self Cite

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Current gene therapy protocols often suffer from an inability to monitor the site, level and persistence of gene expression following somatic DNA delivery. Herpes simplex virus 1 thymidine kinase (HSV1-tk) is currently under intensive investigation as a reporter gene for in vivo imaging of reporter gene expression. The presence of the HSV1-tk reporter gene is repetitively and non-invasively monitored by systemic injection of positron-emitting, radionuclide-labeled thymidine analogues or acycloguanosine HSV1-TK substrates and subsequent detection, by positron emission tomography, of trapped, phosphorylated product. To improve the efficacy of the HSV1-tk PET reporter gene system, both alternative substrates and mutations in the HSV1-tk gene have been described. We used a replication defective adenovirus to deliver the HSV1-sr39tk mutant enzyme and the wild-type HSV1-tk enzyme to mice. HSV1-sr39TK demonstrates greater sensitivity than wild-type HSV1-TK enzyme in vivo, using 9-[(4-[ 18 F]fluoro-3-hydroxymethylbutyl)guanine as probe, following adenovirus-mediated hepatic expression in mice. Using this adenoviral delivery system, the location, magnitude and duration of HSV1-sr39tk PET reporter gene expression could be non-invasively, quantitatively and repetitively monitored for over 3 months by microPET.

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“…17,18 Endogenous cellular receptors are also being developed for in vivo imaging such as the dopamine D2 receptor (D2R) for selective uptake of the radiotracerlabeled antagonist 3-(2 0 -[ 18 F]-fluoroethyl)-spiperone. 19,20 Good correlations with image signal have been demonstrated in vivo, but D2R is also expressed in the brain stratum and in the pituitary glands, 21,22 limiting the specificity of D2R. In addition, D2R reporter gene expression can lead to initiation of intracellular signaling through ligand binding.…”

Section: Introductionmentioning

confidence: 99%

A membrane antibody receptor for noninvasive imaging of gene expression

Roffler

Wang²,

Yu³

et al. 2005

Gene Ther

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Monitoring gene expression is important to optimize gene therapy protocols and ensure that the proper tissue distribution is achieved in clinical practice. We developed a noninvasive imaging system based on the expression of artificial antibody receptors to trap hapten-labeled imaging probes. Functional membrane-bound anti-dansyl antibodies (DNS receptor) were stably expressed on melanoma cells in vitro and in vivo. A bivalent (DNS) 2 -diethylenetriaminepentaacetic 111 Indium probe specifically bound to cells that expressed DNS receptors but not control scFv receptors.Importantly, the 111 In probe preferentially localized to DNS receptors but not control receptors on tumors in mice as assessed by gamma camera imaging. By 48 h after intravenous injection, the uptake of the probe in tumors expressing DNS receptors was 72 times greater than the amount of probe in the blood. This targeting strategy may allow noninvasive assessment of the location, extent and persistence of gene expression in living animals and in the clinic. Gene Therapy (2006) 13, 412-420.

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Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals

Abstract: Reporter genes (eg ␤-galactosidase, chloramphenicol-aceimage reporter gene expression following somatic gene tyltransferase, green fluorescent protein, luciferase) play transfer.

Cited by 332 publications

References 36 publications

Quantitation of HSV mass distribution in a rodent brain tumor model

Quantitation of HSV mass distribution in a rodent brain tumor model

Monitoring adenoviral DNA delivery, using a mutant herpes simplex virus type 1 thymidine kinase gene as a PET reporter gene

A membrane antibody receptor for noninvasive imaging of gene expression

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