Direct correlation between positron emission tomographic images of two reporter genes delivered by two distinct adenoviral vectors

Yaghoubi, SS; Wu, Lily; Liang, Qianwa; Toyokuni, Tatsushi; Barrio, JR; Namavari, Mohammad; Satyamurthy, Nagichettiar; Phelps, M.E.; Hr, Herschman; Gambhir, SS

doi:10.1038/sj.gt.3301490

Cited by 101 publications

(46 citation statements)

References 30 publications

(25 reference statements)

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“…The advantage of Sindbis viral gene therapy vectors for tumor detection is that the vector can markedly amplify the signals by overexpression of the transgene markers. Although luciferase expression may not be suitable for imaging of tumor cells in humans, because of the potential greater depths at which such cells might be found in humans versus mice, other more tissue penetrating reporter genes, such as the herpes simplex virus type-1 thymidine kinase (HSV1-tk) and dopamine-2 receptor (D 2 R) genes, can be incorporated into Sindbis vectors for tumor detection using positron emission topography (22).…”

Section: Discussionmentioning

confidence: 99%

Using Sindbis Viral Vectors for Specific Detection and Suppression of Advanced Ovarian Cancer in Animal Models

et al. 2004

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We studied the therapeutic value of Sindbis vectors for advanced metastatic ovarian cancer by using two highly reproducible and clinically accurate mouse models: a SCID xenograft model, established by i.p. inoculation of human ES-2 ovarian cancer cells, and a syngenic C57BL/6 model, established by i.p. inoculation of mouse MOSEC ovarian cancer cells. We demonstrate through imaging, histologic, and molecular data that Sindbis vectors systemically and specifically infect/detect and kill metastasized tumors in the peritoneal cavity, leading to significant suppression of the carcinomatosis in both animal models. Use of two different bioluminescent genetic markers for the IVIS Imaging System permitted demonstration, for the first time, of an excellent correlation between vector delivery and metastatic locations in vivo. Sindbis vector infection and growth suppression of murine MOSEC tumor cells indicate that Sindbis tumor specificity is not attributable to a species difference between human tumor and mouse normal cells. Sindbis virus is known to infect mammalian cells using the M r 67,000 laminin receptor. Immunohistochemical staining of tumor cells indicates that laminin receptor is elevated in tumor versus normal cells. Down-regulated expression of laminin receptor with small interfering RNA significantly reduces the infectivity of Sindbis vectors. Tumor overexpression of the laminin receptor may explain the specificity and efficacy that Sindbis vectors demonstrate for tumor cells in vivo. We show that incorporation of antitumor cytokine genes such as interleukin-12 and interleukin-15 genes enhances the efficacy of the vector. These results suggest that Sindbis viral vectors may be promising agents for both specific detection and growth suppression of metastatic ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Using Sindbis Viral Vectors for Specific Detection and Suppression of Advanced Ovarian Cancer in Animal Models

et al. 2004

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“…In general, researchers have used four approaches to link the expression of two genes in the context of an adenoviral vector. One approach is based on the use of two adenoviral vectors (Kwong et al, 1997;Yaghoubi et al, 2001). However, this approach cannot guarantee uniform infection of all cells with both vectors because of the relative inefficiency of gene transfer procedures.…”

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confidence: 99%

Circumventing Recombination Events Encountered with Production of a Clinical-Grade Adenoviral Vector with a Double-Expression Cassette

Белоусова

Harris²,

Zinn³

et al. 2006

Mol Pharmacol

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Delivery of multiple exogenous genes into target cells is important for a broad range of gene therapy applications, including combined therapeutic gene expression and noninvasive imaging. Previous studies (Mol Ther 4:223-231, 2001) have described the adenoviral vector RGDTKSSTR with a double-expression cassette that encodes herpes simplex virus thymidine kinase (HSVtk) for molecular chemotherapy and human somatostatin receptor subtype-2 (hSSTR2) for indirect imaging. In this vector, both genes are inserted in place of the E1 region of the adenoviral genome and expressed independently from two cytomegalovirus (CMV) promoters. During production of clinical-grade RGDTKSSTR, we found that the CMV promoters and simian virus 40 (SV40) poly(A) regions located in both expression cassettes provoked homologous recombination and deletion of one of the cassettes. To resolve this problem, we designed a strategy for substituting the duplicate promoters and poly(A) regions. We placed the hSSTR2 gene in the new Ad5.SSTR/TK.RGD vector under the control of a CMV promoter with a bovine growth hormone poly(A) region, whereas the SV40 promoter, enhancer, and poly(A) signal controlled HSVtk expression. This use of different regulatory sequences allowed independent expression of both transgenes from a single adenoviral vector and circumvented the recombination problem. Reconstruction of the vector with a double-expression cassette enables its use in human clinical trials.

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“…Similarly, small antibody fragments, such as scFv, F(ab ¶) 2 , or diabodies, are preferred over intact antibodies to overcome their long whole-body residence time and slow excretion (12). For example, the F(ab ¶) 2 (26,27). Although some extracellular proteases can be imaged using radiolabeled antibodies, such as ProstaScint imaging of the prostate-specific membrane antigen acting as a glutamate carboxypeptidase (28), targeting of proteases is extremely challenging.…”

Section: Probes and Probe Developmentmentioning

confidence: 99%

Nuclear Imaging Probes: from Bench to Bedside

Wester

2007

Clinical Cancer Research

103

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The availability of specific imaging probes is the nuclear fuel for molecular imaging by positron emission tomography and single-photon emission computed tomography. These two radiotracer-based imaging modalities represent the prototype methods for noninvasive depiction and quantification of biochemical processes, allowing a functional characterization of tumor biology. A variety of powerful radiolabeled probesötracersöare already established in the routine clinical management of human disease and others are currently subject to clinical assessment. Emerging from investigations of the genomic and proteomic signatures of cancer cells, an increasing number of promising targets are being identified, including receptors, enzymes, transporters, and antigens. Corresponding probes for these newly identified targets need to be developed and transferred into the clinical setting. Starting with a brief summary of the characteristics and prerequisites for a ''good tracer,'' an overview of tracer concepts, target selection, and development strategies is given. The influence of the imaging concepts on tracer development is also discussed.

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Direct correlation between positron emission tomographic images of two reporter genes delivered by two distinct adenoviral vectors

Cited by 101 publications

References 30 publications

Using Sindbis Viral Vectors for Specific Detection and Suppression of Advanced Ovarian Cancer in Animal Models

Using Sindbis Viral Vectors for Specific Detection and Suppression of Advanced Ovarian Cancer in Animal Models

Circumventing Recombination Events Encountered with Production of a Clinical-Grade Adenoviral Vector with a Double-Expression Cassette

Nuclear Imaging Probes: from Bench to Bedside

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