Abstract

KC Li
NIH Clinical Centre, Bethesda, Maryland, USA

Molecular imaging is an important new technology for imaging gene expression and protein synthesis non-invasively, in vivo with high temporal and spatial resolution. Currently, the focus of molecular imaging has been on constructing new probes that are sensitive to gene expression and that change image contrast when a protein or other factors are up- (or down) regulated in a particular region of tissue. These probes include PET sensitive molecules activated by the upregulation of thymidine kinase, gamma imaging probes that are sensitive to apoptosis using Tc99-Annexin, MRI T1-sensitive probes that can detect the gene marker b-galactosidase (b-gal) for imaging gene transfection, the visualization of the presence of cell-surface molecules using targeted MR imaging agents with high relaxivity, optical probes that can image cell trafficking or gene therapy using molecules such as luciferase or green fluorescent protein (GFP), and other fluorescent probes such as a near-infrared cyanine fluorochromes that are sensitive to the presence of proteases such as cathepsin D.

Approaches to molecular imaging based on the development of probes for specific genes and proteins can have some major limitations. First, many of the materials being studied, e.g., vascular endothelial growth factor (VEGF), often have dramatic effects on changing many other important factors that are not being measured by the probe designed to target VEGF. Secondly, the origin of contrast-enhancement is a complex process related not only to the gene (or protein) expression under investigation, but also to such factors as vascular permeability and interstitial pressures, which have significant influence on the ability to deliver the imaging probes to the intended targets in vivo. These potential limitations are even further magnified when studying new therapeutic interventions such as gene therapy in ischemic tissues, anti-inflammatory agents used for multiple sclerosis, and anti-angiogenesis treatment for cancer, which are areas where molecular imaging probes are being developed to follow new therapeutic interventions.

In this presentation, different approaches for developing various types of molecular imaging probes and their limitations will be discussed.



Keywords: molecular imaging, contrast agent, development