Biomarker Development - Research

Our research is focused on the discovery and development of biomarkers as molecular imaging radiopharmaceuticals with applications in the areas of oncology, infection, and vascular disease. Biomarkers may be defined loosely as imaging agents that localize in mamailian subjects usually by some well-defined biochemical process and whose distribution may be determined by external, noninvasive molecular imaging to provide useful information on physiology and pathology.

Current Projects in the lab

At present, the research of this laboratory is largely, but not exclusively, devoted to investigating the potential of DNA and its analogues (oligomers) as radiolabeled or optically labeled biomarkers. These activities may be further divided into pretargeting applications (P.I.:. Dr. G. Liu) and antisense applications (P.I.: Dr. X. Liu). In addition to a focus on oligomers, the laboratory is also interest in biomarker development involving bacteriophages, for example as is for infection specific imaging or as a tool for biomarker identification by phage display (P.I.: M. Rusckowski).

BiomarkerWhole body 188Re images of two tumored animals obtained simultaneously and superimposed on a photograph taken during imaging to provide accurate registration. The animals were imaged at 19 h post administration with the study animal on the right and the control animal on the left. In both cases, the tumor is in the left thigh.

Detection and treatment of cancers by pretageting has many recognized advantages over conventional antitumor antibody targeting. Pretargeting with complementary oligomers has been developed in this laboratory and is proving to have many advantages over the two earlier approaches. We recently described the first semiemperical model of pretargeting, the first use of linear duplexed oligomers for optical pretargeting, and the first radiotherapy study of oligomer pretargeting. In collaboration with colleagues in the Department of Medicine, we obtained encouraging results in vitro and in vivo of pretargeting applied to measuring the beta cell mass in diabetes.

Nanoparticle This laboratory has taken the lead in developing antisense tumor targeting with radiolabeled DNAs, and have expanded this study into optical antisense imaging. We are exploring the use of antisense targeting of tumor to deposit Auger emitting radionuclides in tumor for improved radiotherapy of micrometastesis. In this connection we are developing a non-covalent streptavidin-based nanoparticle consisting of an anti-tumor antibody, a cell penetrating peptide and the antisense oligomers designed to improve the targeting of tumors following intravenous administration.

GroupPhotoWe are also extending our experience with oligomers by using radiolabeled or fluorescent tagged antisense DNAs against bacterial ribosomal RNA to distinguish infection from inflammation. This laboratory was the first to radiolabel bacteriophages themselves to detect sites of infection through imaging. In addition to oligomers, we have identified unique peptides by phage display methods that serve as markers of cancer cell membrane proteins such as TAG-72 and EGF while others show specificity for arterial vulnerable plaques that will be used to identify clots leading to stroke or heart disease.