Time-resolved fluorescence demonstrates role of cytate in detection of prostate cancer

July 8, 2008--Researchers at the Institute for Ultrafast Spectroscopy and Lasers (IUSL) at The City College of New York (CCNY) have conducted time-resolved fluorescence measurement and optical imaging studies that demonstrate the efficacy of cytate as a fluorescence marker to detect prostate cancer.

Cytate, a contrast agent that conjugates to receptors on prostate cancer cells, exhibited greater fluorescence when applied to cancerous prostate tissue as opposed to normal prostate tissue.

Prostate cancer accounts for approximately 29% of cancer occurrences among men. Current noninvasive detection methods, which include digital exams, blood tests and ultrasound, have limited accuracy.

"There is a need to develop a noninvasive technique for early detection of prostate cancer with higher accuracy and resolution," said Dr. Robert R. Alfano, Distinguished Professor of Science and Engineering and Director of IUSL.

Cytate is dye-peptide conjugate consisting of Indocyanine Green (ICG), an FDA-approved near-infrared dye, and a somatostatin receptor ligand. Somatostatin is a small cyclic neuropeptide that is believed to regulate the production of other hormones and perform an important role in the cancer development. Previous studies had shown that cytate could target somatostatin receptor-rich pancreas tumors in animal model because of its high affinity for the receptors.

The researchers performed ultrafast time-resolved fluorescence polarization measurements on cytate solution as well as on cancerous and normal prostate tissue sample that were stained with cytate. In addition, they conducted fluorescence imaging of two small pieces of cytate-stained normal and cancerous prostate tissue sandwiched between larger pieces of normal prostate tissue.

While the latter technique reveals which sections of tissue indicate presence of cancer, the former how the molecules of cytate around the stained areas are behaving, explained Dr. Wubao Wang, a senior researcher at project leader at IUSL.

The time-resolved fluorescence polarization study found the ratio for peak fluorescence intensity between the cancerous and normal tissue was around 3.57.

"Somatostatin receptors are over-expressed on cancererous cells relative to normal cells, so they adsorb more of the Cytate," Prof. Alfano added. "Cytate essentially is a smart reagent that attaches to cancerous cells. It is an excellent contrast agent because its absorption and fluorescence spectra line in the near-infrared 'tissue optical window (800 nm  1 micron).'"

The next step in the investigation is development of an optical probe called the "photonic finger" that can perform imaging of the prostate from inside the body, he said. The project's ultimate goal is to develop reliable cancer detection techniques based on imaging as an alternative to biopsies.

The research project was supported by a grant from the U.S. Army Medical Research and Material Command. A new grant awarded to Dr. Wang is supporting development of the "photonic finger" near-infrared scanning polarization imaging unit. IUSL is seeking additional grants in biomedical optics to develop the compact unit and photonic explorers.

The research team: included Yang Pu, a Ph.D. candidate in electrical engineering; Dr. Wang; Dr. Bidyut Das, a scientist at IUSL; Dr. Samuel Achilefu, a researcher in the radiology department at Washington University School of Medicine, and Prof. Alfano.

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