Deep Tissue Imaging

Monitoring tumor cell colonization, regression and elimination via light emission is a powerful potential advance in medical imaging. To date, non-invasive fluorescence and/or low light bioluminescence imaging have been the mainstay of preclinical imaging, yet these optical imaging modalities provide little data concerning organs or deep tissues. Optical imaging modalities are limited by light extinction in deep tissues and thus are best applied to small animal imaging and near-surface tissues.

Technologies such as MRI, SPECT, or PET imaging achieve a view at greater tissue depths or in larger animals and humans. Genelux scientists are designing viral and bacterial (live vector) constructs to use with MRI and PET for potential advances in deep tissue imaging.

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PET Imaging

Positron emission tomography (PET) is a nuclear medicine imaging technique which shows metabolic and biologic functions, and is often used to detect certain cancers, identifying lesions and also assessing organ health. PET produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically active molecule. Images of tracer concentration in 3-dimensional or 4-dimensional space (the 4th dimension being time) within the body are then reconstructed by computer analysis.

PET and Live Vector Technology

Genelux researchers have successfully been able, in preclinical studies, to utilize live vectors (e.g. tumor colonizing E.coli bacterum) in conjunction with radiotracers to perform PET imaging to visualize malignant tissues. This system, if one day applied in larger animals and humans has the potential to track bacteria and their gene expression during tumor colonization or disease progression, while providing concomitant anatomical information

PET Image of mouse bearing tumors, one injected with virus expressing hNET (right front leg armpit in sketch), and the other no virus. The radiotracer [124I]-MIBG allows for PET visualization of the virus-infected tumor in the color image (tumor is bright white image, top right)

MoBiVir Program

Genelux GmbH in Bernried, Germany is developing deep tissue imaging applications for PET based on the Company’s vaccinia virus platform, leading a consortium program entitled Research of New Recombinant Vaccinia Viruses and Radiotracers for the Molecular PET-Diagnostics of Tumors (Acronym: MoBiVir) under the grant 13N10451 from the German Ministry for Education and Research (BMBF).

The project targets collaborative research and development of all enabling components of a novel PET imaging system based on the Genelux platform technology, including reagents, hardware, software, protocols and working together with scientists from:

–     ABX (Radeberg, Germany), a radiochemical and precursor provider;

–     Raytest, GmbH (Straubenhardt, Germany), an equipment provider;

–     University Clinics for Nuclear Medicine (University of Wurzburg and

–     University of Freiburg, Germany); and,

–     Bayer Schering Pharma AG (BSP), associated and consulting member.

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MR Imaging

Magnetic resonance imaging (MRI) is primarily a noninvasive medical imaging technique used in radiology to visualize detailed internal structure and limited function of the body. It is the preferred imaging technology for evaluating soft tissues and organs and, with respect to oncology, detects primarily soft tissue masses and brain tumors.

MRI uses a strong magnetic field to align the nuclear magnetization of (usually) hydrogen atoms in water in the body. Radio frequency (RF) fields are used to systematically alter the alignment of this magnetization. This causes the hydrogen nuclei to produce a rotating magnetic field detectable by the scanner. MRI provides much greater contrast between the different soft tissues of the body than other techniques (e.g. CT), and is used in oncological, neurological (brain), musculoskeletal and cardiovascular imaging.

MRI and Live Vector Technology

Genelux scientists are developing tumor-colonizing live vector systems to work with MRI technology to achieve improved deep tissue tumor detection. Recent studies have shown that human ferritin (a molecule with iron accumulation properties) can be used as a reporter of gene expression for MRI. To this end, our researchers examined three ferritin type molecules, including bacterioferritin occurring in bacteria as a reporter of gene expression. After injecting tumor-bearing mice with probiotic E. coli Nissle 1917 bacteria over expressing each of the three molecules, it was determined that bacterioferritin provided the highest contrast in colonized tumors.

This research suggests that, in the future, tumor-colonizing live vector systems (e.g. bacteria) may be used in conjunction with MRI contrast enhancers like ferritin to become an important procedure for diagnosis and therapy of tumors in humans and for monitoring infectious disease models in larger mammals.