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  • Acquired Diseases
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Quantitation of HSV mass distribution in a rodent brain tumor model

Gene Therapy volume 7, pages 1648–1655 (2000)Cite this article

Abstract

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 111in-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, a synthetic bradykinin analog, with the virus, resulted in slightly increased tumor delivery of 0.17 ± 0.10% id/g (p 0.05) at 1 h. the 1 h organ distribution after intra-arterial injection (%id/organ) was as follows: liver 27.3 ± 2.86%, lung 2.10 ± 0.68% and kidney 1.78 ± 1.60% with lesser amounts in other organs. when virus was injected directly into the tumor, 71% of virus remained in tumor at 24 h (590 ± 212 %id/g, consistent with the small tumor mass containing most of the virus) with the following distribution regions: tumor > border zone > normal brain (99:40:1). These studies are the first quantitative mass distribution studies of HSV vectors in an experimental brain tumor model. Localization and quantitation of viral accumulation in vivo will enable detailed analysis of viral and organ interactions critical for advancing the therapeutic use of vectors.

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Acknowledgements

The help of Dr Cliff Eskey in data analysis is gratefully acknowledged. Dr Anna Moore kindly provided the cell lines used. Ms Deborah Schuback prepared and titered the hrR3 viral stocks. Thanks to Dr Alex Bogdanov for helpful discussions. These studies were supported in part by grants PO1CA48729, PO1CA69246 and RO1NS35258. NGR was supported in part by FKZ 2794A/0087H from the State of Saxony-Anhalt.

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  1. N G Rainov

    Present address: Department of Neurosurgery, Faculty of Medicine, Martin-Luther-University, Halle (Saale), Germany

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  1. Center for Molecular Imaging Research, Charlestown, MA, USA

    D Schellingerhout & R Weissleder

  2. Molecular Neurogenetics Unit, Neuroscience Center, Massachusetts General Hospital,

    N G Rainov & X O Breakefield

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Schellingerhout, D., Rainov, N., Breakefield, X. et al. Quantitation of HSV mass distribution in a rodent brain tumor model. Gene Ther 7, 1648–1655 (2000). https://doi.org/10.1038/sj.gt.3301272

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