Quantitation of HSV mass distribution in a rodent brain tumor model

Schellingerhout, Dawid; Rainov, Nikolai G.; Breakefield, Xandra O.; Weissleder, Ralph

doi:10.1038/sj.gt.3301272

Cited by 46 publications

(33 citation statements)

References 41 publications

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“…40 As expected, most of the virus went to the liver, 2.6%/g, followed by the lung, spleen, and kidney. In this model, there was only a small increase in the amount of virus in the brain tumor after BBBD with RMP7 (0.1 versus 0.17%/g).…”

Section: Oncolytic Hsv Therapy Of Brain Tumors After Bbbd R Liu Et Alsupporting

confidence: 67%

“…In this model, there was only a small increase in the amount of virus in the brain tumor after BBBD with RMP7 (0.1 versus 0.17%/g). 40 This small difference may have been due to the tumor model and the fact that this assay does not distinguish infectious from non-infectious virus or infected cells from extracellularly trapped virus. Interestingly, there was a 4two-fold decrease in the liver after BBBD.…”

Section: Oncolytic Hsv Therapy Of Brain Tumors After Bbbd R Liu Et Almentioning

confidence: 99%

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Intracarotid delivery of oncolytic HSV vector G47Δ to metastatic breast cancer in the brain

2005

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Delivery of viral vectors to tumors in the brain is a challenge, especially via systemic administration, which is key to targeting the invasive margins of malignant glioma and the multiple foci of metastatic disease. Like for other cancer therapeutics, the blood-brain barrier or even the bloodtumor barrier significantly limits delivery and efficacy. Bloodbrain barrier disruption (BBBD) is one strategy for transiting the cerebrovasculature. G47D is a third-generation oncolytic replication-competent herpes simplex virus (HSV) vector, containing deletions of the g34.5 and a47 genes and an inactivating LacZ insertion in UL39 (ICP6). Intracarotid artery delivery of G47D after BBBD with 25% mannitol significantly extended the life of nude mice bearing intracerebral human MDA-MB-435 breast tumors, whereas, G47D injection contralateral to the tumor, in the absence of mannitol or mannitol alone had no effect on survival. G47D replication was extensive after BBBD, as visualized by X-gal staining. Staining of peripheral organs, lung and liver, was minimal and not altered by BBBD. This is the first demonstration of intracarotid arterial delivery of oncolytic HSV vectors and antitumor efficacy in a mouse model and opens the door to the use of mouse syngenic tumor models and transgenic/ knockout animals. Gene Therapy (2005) 12, 647-654.

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Section: Oncolytic Hsv Therapy Of Brain Tumors After Bbbd R Liu Et Alsupporting

confidence: 67%

Section: Oncolytic Hsv Therapy Of Brain Tumors After Bbbd R Liu Et Almentioning

confidence: 99%

Intracarotid delivery of oncolytic HSV vector G47Δ to metastatic breast cancer in the brain

2005

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“…So far, viral vector imaging has only been achieved using whole-body nuclear imaging of rat 11 and rat brain. 12 Despite their sensitivity, the spatial resolution of nuclear imaging is poor (several millimeters), and the presence of ionizing radiation can be potentially harmful for cells. Also, the number of nuclear imaging scanners is clinically limited compared to MRI.…”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance imaging of viral particle biodistribution in vivo

et al. 2006

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We describe here a technique for the visualization of viral vector delivery by magnetic resonance imaging (MRI) in vivo. By conjugating avidin-coated baculoviral vectors (Baavi) with biotinylated ultra-small superparamagnetic iron oxide particles (USPIO), we are able to produce vector-related MRI contrast in the choroid plexus cells of rat brain in vivo over a period of 14 days. Ten microlitres of 2.5 Â 10 10 PFU/ml nuclear-targeted LacZ-encoding Baavi with bUSPIO coating was injected into rat brain ventricles and visualized by MRI at 4.7 T. As baculoviruses exhibit restricted cell-type specificity in the rat brain, altered MRI contrast was detected in the choroid plexus of the injected ventricles. No specific signal loss was detected when wild-type baculoviruses or intact biotinylated USPIO particles were injected into the lateral ventricles. Cryosectioned brains were stained for nucleartargeted b-galactosidase gene expression, which was found to colocalize with MRI contrast. This study provides the first proof of principle for robust and non-invasive viral vector MRI by using avidin-displaying viruses in vivo. Considering the widespread use of MRI in current medical imaging, the approach is likely to provide numerous future applications in imaging of therapeutic gene transfer.

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“…SPECT imaging involves the rotation of a photon detector array around the body to track the position and concentration of radionuclide distribution from multiple angles. SPECT has been used to follow the distribution of antibodies to the transmembrane receptor kinase, ERBB2, 28 herpes simplex virus 29 and receptor-binding molecules (Astatine-211). 30 SPECT has been used to image cell-surface-expressed receptors and transporters.…”

Section: Petmentioning

confidence: 99%