IMAGING TECHNOLOGY AND MOLECULAR PROBES ADVANCE GASTROINTESTINAL THERAPY

New developments in imaging tech­nology have enabled physicians to identify cancer in its earliest manifes­tations, which is critical for treatment. In addition, a more thorough under­standing of the numerous molecular pathways involved in tumor cell proliferation has allowed physicians to adopt a personalized approach with targeted cancer therapies.

Thomas D. Wang, MD, PhD, associate professor of internal medicine, biomedical engineering and mechanical engineering, and H. Marvin Pollard collegiate professor of endoscopy research at the University of Michigan Health System, is devel­oping very specific molecular probes to be used in conjunction with new optical imaging to identify precancerous lesions in the gastrointestinal tract.

Dr. Wang, Xiyu Duan and Gaoming Li, pictured left to right, work with a laser as part of Dr. Wang’s research.

“We are currently developing peptides that bind to molecular targets expressed in diseases of the biliary tract, colon, esophagus, and liver,” said Dr. Wang, a gastroenterologist whose research has centered on molecular imaging.

PEPTIDE-BASED PROBES

Although most existing targeted cancer thera­pies are based on monoclonal antibodies that attach to target proteins on the exterior of cancer cells, Dr. Wang is concentrating on peptide-based compounds that are considerably smaller.

“These peptide-based probes provide an attrac­tive alternative for visualizing tissue targets that would otherwise be difficult to penetrate or access,” Dr. Wang said. “This work alters current diagnostic paradigms because diagnoses can now be made based on microscopic increases in the expression of molecular targets specific to certain diseases rather than on the gross visible appear­ance of mass lesions.”

Peptides also are safe for systemic use and are less immunogenic than antibodies. Additionally, peptides can be transformed anatomically to increase stability against proteolytic degradation and can be labeled with fluorophores that will permit imaging several targets at the same time.

Dr. Wang is part of a collaboration that is respon­sible for “developing novel molecular imaging methodologies to visualize cell surface targets that are either gene amplified and/or highly overexpressed in EAC [esophageal adenocarci­noma],” as compared with Barrett’s esophagus. These cell surfaces will be seen using “highly specific peptides that are fluorescently labeled for real-time endoscopic imaging to rapidly assess esophageal mucosa” for the existence of early neoplasia.

Dr. Wang hopes that with additional research and development of peptide-based probes for molec­ular imaging, physicians will have a more precise representation of cellular and molecular activities in all areas of the GI tract.

“We have developed novel molecular probes that bind to cell surface targets that are overexpressed in a number of human diseases,” he said. “I expect to find new uses for these molecular probes to detect diseases beyond their original purpose for development.”

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