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Vaccinia virus-mediated melanin production allows MR and optoacoustic deep tissue imaging and laser-induced thermotherapy of cancer.

Abstract
We reported earlier the delivery of antiangiogenic single chain antibodies by using oncolytic vaccinia virus strains to enhance their therapeutic efficacy. Here, we provide evidence that gene-evoked production of melanin can be used as a therapeutic and diagnostic mediator, as exemplified by insertion of only one or two genes into the genome of an oncolytic vaccinia virus strain. We found that produced melanin is an excellent reporter for optical imaging without addition of substrate. Melanin production also facilitated deep tissue optoacoustic imaging as well as MRI. In addition, melanin was shown to be a suitable target for laser-induced thermotherapy and enhanced oncolytic viral therapy. In conclusion, melanin as a mediator for thermotherapy and reporter for different imaging modalities may soon become a versatile alternative to replace fluorescent proteins also in other biological systems. After ongoing extensive preclinical studies, melanin overproducing oncolytic virus strains might be used in clinical trials in patients with cancer.
AuthorsJochen Stritzker, Lorenz Kirscher, Miriam Scadeng, Nikolaos C Deliolanis, Stefan Morscher, Panagiotis Symvoulidis, Karin Schaefer, Qian Zhang, Lisa Buckel, Michael Hess, Ulrike Donat, William G Bradley, Vasilis Ntziachristos, Aladar A Szalay
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 110 Issue 9 Pg. 3316-20 (Feb 26 2013) ISSN: 1091-6490 [Electronic] United States
PMID23401518 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Melanins
Topics
  • Animals
  • HeLa Cells
  • Humans
  • Hyperthermia, Induced (methods)
  • Infrared Rays
  • Lasers
  • Magnetic Resonance Imaging
  • Melanins (biosynthesis)
  • Mice
  • Neoplasm Metastasis
  • Neoplasms (metabolism, pathology, therapy)
  • Photoacoustic Techniques (methods)
  • Vaccinia virus (metabolism)

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