Biological Molecular Imaging Section

Molecular imaging allows detection of specific targets in vivo, including visualization of the presence of targets, as well as the quantification of their spatial and temporal distribution. A target may be a single key protein or a particular pathway related to certain pathological processes.  Our lab develops probes of small organic molecules, polypeptides, proteins, antibodies or aptamers by phage peptide display library screening, single chain antibody library screening, and systematic evolution of ligands by exponential enrichment (SELEX). The newly developed probes are then modified and optimized for in vivo molecular imaging application.

Fluorophores, isotopes, and other detectable labels are most commonly introduced into a protein through in vitro modifications with suitable amine or thiol reactive reagents. Non-specific labeling of protein probes will cause heterogeneity and inaccuracy of quantification in the imaging process. Our lab engineers protein probes to accomplish site-specific modification. For example, with a system utilizing an mRNA template with an amber codon (UAG), instead of a normal initiating codon (AUG) and a complementary misaminoacylated initiator suppressor tRNA capable of initiating protein synthesis from the UAG codon, an artificial amino acid can be introduced into the N-terminal of synthesized proteins. Enzymatic post-translational modification of proteins utilizing inteins-mediated protein splicing is an alternative approach for site-specific labeling.

Therapeutic efficacy is a key question that needs to be answered for ever drug or drug candidate. Molecular imaging is able to provide information to evaluate pharmacological effects. For instance, solid tumors are often characterized by having high glucose utilization, tumor cell proliferation, hypoxia with sustained angiogenesis and evasion of apoptosis. The influence of compounds targeting these characteristics of cancer biology can be selectively visualized by molecular imaging techniques. Examples include FDG PET to image glucose transport and metabolism, and FLT PET to evaluate the proliferating status. Additionally, some imaging strategies can focus on one particular pathway such as apoptosis and hypoxia or a single molecular target to access specific drugs.

As a unique branch of molecular imaging, various reporter genes have been developed, and expression of reporter genes can be evaluated by multiple imaging modalities, including optical imaging, SPECT/PET or MRI. With split reporter gene or bioluminescence resonance energy transfer (BRET) system, protein-protein interactions can be visualized in living organisms.  Our lab develops and applies reporter gene imaging to corroborate probe-based non-invasive imaging.