Fluorescent probe for breast cancer detection
Mammography is heralded as the best way to detect breast cancer early, and tumors found early are easier to treat successfully. However, the limitations of mammography — such as a 22 percent false-negative rate for women under 50 — have led researchers to look for other ways to screen and characterize breast cancer. Researchers at the University of Pennsylvania in Philadelphia and at University College London have coupled fluorescence diffuse optical tomography with the molecular contrast agent indocyanine green to create images of human breast cancer.
Using fluorescence diffuse optical tomography combined with indocyanine green (ICG), researchers can detect breast cancer by measuring total hemoglobin concentration, blood oxygenation, absorption at 786 nm and ICG concentration. Reprinted with permission of Optics Express.
The method was demonstrated by a team of scientists led by Arjun G. Yodh and including Alper Corlu, Regine Choe, Turgut Durduran, Mark A. Rosen, Mitchell D. Schnall, Martin Schweiger and Simon R. Arridge. Yodh explained that adding indocyanine green, a fluorophore approved for medical use since 1956, enhances the optical method’s specificity and sensitivity to breast tumors. Because tumors have leaky blood vessels, the fluorophore accumulates more in tumors than in normal tissue, which improves the contrast of the tumor. The ability to image in vivo fluorescence opens the door to probing the cellular microenvironment for oxygen pressure, pH and calcium concentration.
The researchers built a custom imaging instrument consisting of a table on which the patient lies facedown. The patient’s breasts are suspended in a box filled with a fluid that has optical properties similar to those of human tissue. One side of the box has a soft compression plate, and the other has a viewing window. The compression plate contains 45 optical fibers measuring 200 μm in diameter for excitation light, and nine fibers for detection. A Princeton Instruments CCD camera equipped with an 830-nm bandpass and a 785-nm notch filter is mounted outside the viewing window. A diode laser from CrystaLaser of Reno, Nev., operating at 786 nm with average power of 10 mW provided excitation.
After testing the system on tissue phantoms, the researchers used the instrument with three volunteers, ages 46, 54 and 52, all with significant breast cancer. Using the system, the investigators compared total hemoglobin concentration, blood oxygenation levels, tissue scattering and indocyanine green concentration with conventional MRI and mammograms. In each case, the system clearly resolved the cancer. However, the results indicate that a single endogeneous parameter, such as total hemoglobin concentration, alone may not be sufficient. Instead, the success of the system may depend on combining several parameters including indocyanine green.
Choe explained that the system’s structural resolution is roughly 5 to 10 mm. “If the contrast is increased, the resolution and sensitivity can be increased too,” she explained. “One way to increase the contrast is through the development of novel molecular probes.” Although the researchers have not focused on creating new probes, scientists elsewhere are working on agents that selectively bind to tumor cells using monoclonal antibodies or tumor-specific peptides. Joining these probes with near-infrared fluorochromes would enable much more specific fluorescence imaging based on diffuse optical tomography.
From here, Yodh said that the group plans to continue pilot studies, to explore the difference in the indocyanine green wash-out rate between normal and cancerous tissue, to carry out fluorophore lifetime studies and to test new fluorescent probes.
Optics Express, May 2007, pp. 6696-6716.
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