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Molecular Spies for Personalised Imaging

By Prof Dr Hans Ringertz, MD, Phd, Lecture at the STAR Programme 2006

(Reproduced with permission)

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If an alien civilisation from outer space would approach the earth and wanted to understand all aspects of life on the planet it would not be enough to study the geography in more or less detail. Even if the morphology of our buildings, vehicles, and biological creatures could be observed from outer space, the detailed function of our different societies would not be even approxi¬mately understood. In order to fully understand our life, the alien civilisation would have to send spies disguised as humans down to earth to live their lives in our different environments.

In the same way, morphology and external physiological observations are not enough to study the detailed function of the human body on the cellular and molecular level the genomic and proteomic cellular function in addition to the microscopically observed morphology.

The course of biology has been driven by morphological observations ever since the first microscope was built in the late sixteenth century. It would have been hard to conceive even a couple of decades ago the extent to which progress would be made in observations of living subjects afforded by modern-day imaging techniques. Molecular imaging is the latest addition in this astounding imaging evolution, bringing observations in living subjects to a more meaningful dimension.

For the first time, molecular imaging is helping to shed new light on function in addition to structure in intact living subjects by way of novel approaches that visualize and characterize living biological systems at the cellular and even molecular levels.

Exactly What Is Molecular Imaging?

Molecular imaging is a rapidly emerging biomedical research discipline that may be defined as the visual representation, characterization, and quantification of biological processes at the cellular and sub-cellular levels within intact living organisms. This is a novel multidisciplinary field, where the images produced reflect cellular and molecular pathways and in vivo mechanisms of disease present within the context of physiologically authentic environments. The term ‘molecular imaging’ implies the convergence of multiple image-capture techniques, basic cell/molecular biology, chemistry, pharmacology, medical physics, biomathematics, and bioinformatics into a new imaging paradigm.

Current imaging technologies rely mostly on non-specific macroscopic physical, physiological, or metabolic changes that differentiate pathological from normal tissue rather than identifying specific molecular events (e.g. gene expression) responsible for disease. Molecular imaging usually exploits specific molecular probes as the source of image contrast. This change in emphasis from a non-specific to a specific approach represents a significant paradigm shift, the impact of which is that imaging can now provide the potential for understanding of integrative biology, earlier detection and characterisation of disease, and evaluation of treatment.

The emergence of molecular imaging strategies is largely due to recent unprecedented advances in molecular and cell biology techniques, the use of transgenic animal models, availability of newer imaging drugs and probes that are highly specific, and successful development of small-animal imaging instrumentation. These factors, along with continued expansion of scientific horizons in the current post-genomic era, have been pivotal in the drive toward a new standard that allows linking established in vitro and cell culture experimental assays to imaging studies within living subjects.

This now creates the possibility of achieving several important goals in biomedical research, namely:

to develop non-invasive in vivo (within a living organism, in this case, human body) imaging methods that re¬flects specific cellular and molecular processes, e.g. gene expression, or more complex molecular interactions such as protein-protein interactions;
to monitor multiple molecular events near-simultaneously;
to follow trafficking and targeting of cells;
to optimize drug and gene therapy;
to image drug effects at a molecular and cellular level;
to assess disease progression at a molecular pathological level; and
to create the possibility of achieving all of the above goals of imaging in a rapid, reproducible, and quantitative manner, so as to be able to monitor time-dependent experimental, developmental, environmental, and therapeutic influences on gene products in the same animal or patient.

For radiologists around the world this is the time to focus on the recent advances in the rapidly expanding field of molecular imaging. Advances in the field should lead to significant contributions in fundamental biology and the clinical management of cancer, neurological diseases, as well as many other disease states but we need to be prepared

to oversee the imaging aspects and
to lead the following translational research.

SUGGESTED READING

Herschman HR
Molecular Imaging: Looking at Problems, Seeing Solutions.
Science 24, 2003; 302(5645):605-608
Massoud T, Gambhir SS
Molecular Imaging in Living Subjects: Seeing Fundamental Biological Processes in a New Light.
Genes & Development 2003; 17(5):545-580
Gambhir SS
Molecular Imaging of Cancer with Positron Emission Tomography.
Nature Reviews Cancer 2002; 2(9):683-693
Weissleder R
Scaling down imaging: molecular mapping of cancer in mice.
Nature Reviews Cancer 2002; 2:11-18
Weissleder R
A clearer vision for in vivo imaging.
Nature Biotechnology 2001; 19:316-317

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Last Updated:
Monday, 20 March 2006