How to visualize tumors in vivo
One of the challenges of cancer therapy is to obtain a high accuracy map of the tumor distribution. This is further complicated by by the movement of tumor cells from their initial site to distal sites, via the process of metastasis. Whole body imaging techniques are excellent, however they may miss cancers that very closely resemble the tissues that surround them. A new study summarized at Science Daily, from the open access journal PLoS One, describes a novel way for trying to obtain images of tumors using non-invasive means.
Previous research has demonstrated that bacteria that are injected will with high efficiency begin to associate with tumors. Indeed, a posting here on the BIO230 blog last summer, found that the association of strictly anaerobic bacteria within the hypoxic environment found in a solid mass tumor could potentially be used as a novel form of anti-cancer therapy. This newer research is utilizing harmless bacteria normally found as part of the human gut flora, and are frequently taken as part of “probiotic” therapy to treat gastrointestinal disease. These bacteria do not normally cause human disease, and when they are injected into the circulatory system in mice, they appear to hone in on solid mass tumors.
The study reported here has taken advantage of that observation, and adapted it to develop a novel way to see tumors in a live patient. Several species of harmless bacteria (Escherichia coli, Bifidobacterium longum, and an attenuated strain of Salmonella Typhimurium) were modified molecularly to express the firefly luciferase gene. When these bioluminescent strains of bacteria are injected into a laboratory mouse, the bacteria quickly migrate and localize in solid mass tumors if they are present. Bioluminescence can then be detected through tissue by a technique called Bioluminescent Imaging (BLI) coupled with micro computerized tomography (μCT). The image at the top of this posting is taken from the PLoS article, and the middle panel (orange signal) indicates the localization of bacteria. The left panel indicates the location of bioluminescent tumor cells, and it is very apparent that the bacteria co-localize with the tumor mass.
It is important to note that tumor masses are bioluminescent on their own; the cancer cell lines in this study are engineered to give them that property, and consequently the colocalization of the tumor cells and bacteria seen above could potentially be a laboratory artifact. Control experiments in the study did eliminate this as a possibility. Further experiments will need to address whether the approach would be useful for spontaneously arising tumors of animals (and in humans!), and what the utility of the imaging technique would be for non-solid mass tumors.
I’ll use this opportunity to give a shout-out to my wife’s colleagues at the University of Virginia, with an article published in Cancer Research in 2008. She used the BLI technique to follow the development of brain tumors in mice, in a manner very analogous to what is summarized in the PLoS study. The top panel to the left is bioluminescence of engineered tumors, as visualized through the skull of living mice. The technique of course enables the researcher to follow the animal as the tumor continues to develop, and allows the researcher to begin to develop therapies designed to shrink and eliminate the tumor. The “old-school” approach in these experiments is detailed in the right hand panel, which is a histological post-mortem analysis, and only offers an endpoint in the tumor progression. As such, the utility of therapeutics can only be assessed indirectly.
Posted on January 26, 2012, in Microbes in the News, Strange but True and tagged Bifidobacterium longum, Bioluminescence, Cancer, Escherichia coli. Bookmark the permalink. Comments Off on How to visualize tumors in vivo.