Biomedical Engineering Reference
In-Depth Information
13
ImagIng genetIc InformatIon
John-Stephen Taylor
Department of Chemistry, Washington University, St. Louis, MO, USA
13.1
IntroductIon
Almost all disease states can be attributed to genetic or epigenetic information found
within the diseased host that is different from that of the normal host, with the exception
of prion diseases [1-4]. The disease-causing genetic information might reside in the
genomic DNA or RNA, or in a virus, bacterium, or other pathogen, or from alterations
in the methylation pattern of DNA, which in turn alters RNA expression levels. The
altered or foreign genetic information can result in the synthesis of mutated or nonna-
tive proteins or cause changes in the expression of normal proteins that in turn can
affect the expression of other proteins and downstream metabolites that themselves
can cause alterations in protein expression and epigenetic modifications. As a result,
diseased tissue in a person can be imaged by the accumulation of a probe targeted to
a disease-specific biomolecule by a process known as molecular imaging [5, 6]
(Fig. 13.1). Because proteins are present in much higher concentration than the DNA
or mRNA that encodes them, most imaging agents for diseases are targeted to disease-
specific proteins. Of the many possible protein targets, those that are on a cell surface
are the most desirable target because they are the most accessible and don't require
intracellular entry of the imaging agent. The diseased cell or disease-causing organism
can then be recognized by a small molecule ligand for a receptor or enzyme [7] or by
a protein binding molecule, such as an antibody, minibody [8], or aptamer [9, 10].
If the diseased cell does not express a unique or overexpressed cell surface target
that is specific for the disease state, then an internal target is necessary. Small molecule
ligands for target proteins make excellent imaging agents because they are often
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