What does the natural imaging potential of melanin have in common with the ability of recombinant Vaccinia viruses to target and replicate within tumor cells? Perhaps nothing, until they are combined. Now, thanks to the work of scientists at Genelux Corp., these factors have enabled cancer theranostics: treatment and deep tissue imaging, as a newly published study explains.1
Melanin is a pigment produced by melanoma and other types of cancer that appears very bright in magnetic resonance imaging (MRI). Its expression by the engineered virus achieved concentrations sufficient to enable enhanced MRI and optoacoustic (a.k.a. photoacoustic) imaging, as well as thermotherapy (laser-induced thermal lysis) of melanin-producing tumors. The approach can serve as a visible marker during surgery, as a mediator of laser-induced phototherapy, and as a reporter (an easily identified and measurable gene product). This achievement results from characteristics of the Vaccinia virus, which replicates only in the cell's cytoplasm: It has large foreign-gene-carrying capacity and efficiently colonizes tumors, according to Aladar Szalay, Ph.D., senior study author and founder and CEO of Genelux.
Researchers at the company have been working to develop recombinant Vaccinia virus strains for deep tissue imaging. To facilitate melanin production, they inserted the genetic information encoding melanin-producing enzymes into the genome of strains able to infect cancer cells. MRI effectively detected the resulting melanin production and localization in both solid tumors and very small metastases. Szalay noted that the experiments enable design and production of imaging agents without needing added substrates, which currently limit the utility of imaging agents.
The team also used near-infrared (NIR) lasers to increase the temperature of the light-absorbing, melanin-producing tumor cells and tissues to >150°F, which effectively destroyed the tumors in live animals. By comparison, healthy cells allowed little light absorption and could only be heated by a few degrees; no cell death was observed.
The study also found new melanin-encoding viral strains useful for generating specific signals in multispectral optoacoustic tomography (MSOT), a novel technology for high-resolution, deep-tissue molecular imaging that generates 3D views of site(s) absorbing the greatest amount of light. MSOT signals were very intense in virus-colonized, melanin-producing tumors and metastases, allowing excellent imaging. William G. Bradley, M.D., Ph.D., FACR, chair of the Department of Radiology at the University of California, San Diego (UCSD) School of Medicine and study co-author, said that the use of melanin-producing enzymes as reporters will likely have a significant impact on basic research, and also possibly aid medical applications, beginning with clinical trials for cancer. "One day we may see laser-mediated thermal ablation of melanin-producing tissues when surgical removal is not an option," he said.
1. J. Stritzker et al., Proc. Nat. Acad. Sci., 110, 9, 3316–3320 (2013).