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

被引：98

作者：

Stritzker, Jochen ^{[1
,2
]}

Kirscher, Lorenz ^{[2
]}

Scadeng, Miriam ^{[3
]}

Deliolanis, Nikolaos C. ^{[4
,5
,6
]}

Morscher, Stefan ^{[4
,5
,7
]}

Symvoulidis, Panagiotis ^{[4
,5
]}

Schaefer, Karin ^{[4
,5
]}

Zhang, Qian ^{[1
]}

Buckel, Lisa ^{[2
]}

Hess, Michael ^{[2
]}

Donat, Ulrike ^{[2
]}

Bradley, William G. ^{[8
]}

Ntziachristos, Vasilis ^{[4
,5
]}

Szalay, Aladar A. ^{[1
,2
,9
]}

机构：

[1] Genelux, San Diego, CA 92109 USA

[2] Univ Wurzburg, Dept Biochem, Bioctr, D-97074 Wurzburg, Germany

[3] Univ Calif San Diego, Ctr Funct MRI, La Jolla, CA 92093 USA

[4] Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, D-85764 Neuherberg, Germany

[5] Tech Univ Munich, D-85764 Neuherberg, Germany

[6] Fraunhofer Project Grp Automat Med & Biotechnol, D-68167 Mannheim, Germany

[7] iThera Med, D-85764 Neuherberg, Germany

[8] Univ Calif San Diego, San Diego Med Ctr, Dept Radiol, San Diego, CA 92103 USA

[9] Univ Calif San Diego, Moores Canc Ctr, Dept Radiat Oncol, La Jolla, CA 92093 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 09期

基金：

欧洲研究理事会;

关键词：

translational medicine; personalized medicine; diagnosis; photoacoustic; whole-body imaging; GENE; EXPRESSION; TUMORS;

D O I：

10.1073/pnas.1216916110

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：3316 / 3320

页数：5