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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.

SUBMITTER: Stritzker J

PROVIDER: S-EPMC3587225 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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

Stritzker Jochen J Kirscher Lorenz L Scadeng Miriam M Deliolanis Nikolaos C NC Morscher Stefan S Symvoulidis Panagiotis P Schaefer Karin K Zhang Qian Q Buckel Lisa L Hess Michael M Donat Ulrike U Bradley William G WG Ntziachristos Vasilis V Szalay Aladar A AA

Proceedings of the National Academy of Sciences of the United States of America 20130211 9

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 pr ...[more]

PMID: 23401518

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Project description:ObjectivesTo develop, test and evaluate improved 2D and 3D protocols for proton resonance frequency shift magnetic resonance temperature imaging (MRTI) of laser interstitial thermal therapy (LITT). The objective was to develop improved MRTI protocols in terms of temperature measurement precision and volume coverage compared to the 2D MRTI protocol currently used with a commercially available LITT system.MethodsFour different 2D protocols and four different 3D protocols were investigated. The 2D protocols used multi-echo readouts to prolong the total MR sampling time and hence the MRTI precision, without prolonging the total acquisition time. The 3D protocols provided volumetric thermometry by acquiring a slab of 12 contiguous slices in the same acquisition time as the 2D protocols. The study only considered readily available pulse sequences (Cartesian 2D and 3D gradient recalled echo and echo planar imaging [EPI]) and methods (partial Fourier and parallel imaging) to ensure wide availability and rapid clinical implementation across vendors and field strengths. In vivo volunteer studies were performed to investigate and compare MRTI precision and image quality. Phantom experiments with LITT heating were performed to investigate and compare MRTI precision and accuracy. Different coil setups were used in the in vivo studies to assess precision differences between using local (such as flex and head coils) and non-local (i.e., body coil) receive coils. Studies were performed at both 1.5 T and 3 T.ResultsThe improved 2D protocols provide up to a factor of two improvement in the MRTI precision in the same acquisition time, compared to the currently used clinical protocol. The 3D echo planar imaging protocols provide comparable precision as the currently used 2D clinical protocol, but over a substantially larger field of view, without increasing the acquisition time. As expected, local receive coils perform substantially better than the body coil, and 3 T provides better MRTI accuracy and precision than 1.5 T. 3D data can be zero-filled interpolated in all three dimensions (as opposed to just two dimensions for 2D data), reducing partial volume effects and measuring higher maximum temperature rises.ConclusionsWith the presented protocols substantially improved MRTI precision (for 2D imaging) or greatly improved field of view coverage (for 3D imaging) can be achieved in the same acquisition time as the currently used protocol. Only widely available pulse sequences and acquisition methods were investigated, which should ensure quick translation to the clinic. Lasers Surg. Med. 51:286-300, 2019. © 2019 Wiley Periodicals, Inc.

Dataset Information

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

Publications

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

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