image: Researchers developed a pill that lights up cancerous tumors in a mouse's breast tissue under near-infrared light. view more
Credit: Thurber lab
SAN DIEGO, March 15, 2016 -- The ongoing debate about breast cancer diagnostics has left many women confused -- particularly over what age they should get mammograms and who needs treatment. An issue with current methods is that they often identify lumps but cannot conclusively pinpoint which ones are cancerous. To help resolve this uncertainty, researchers have developed a pill that could improve imaging techniques so that only cancerous tumors light up.
Today, the researchers report their diagnostic approach at the 251st National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 12,500 presentations on a wide range of science topics.
"There's a lot of controversy right now about when patients should start screening for breast cancer," says Greg Thurber, Ph.D. "Screening can potentially catch the disease early in some patients, but false positives can lead to unnecessary, aggressive treatments in patients who don't need them. We don't know how to select the right patients to treat. Our work could help change that."
Breast cancer is the second most common cancer in women. Mammograms, the current standard for screening, are X-rays of breast tissue. They give doctors information about a lump's location and size, but they can't distinguish between cancerous and benign growths. To find out more, doctors have to take a biopsy, which can involve needles or surgery. Biopsies, however, aren't 100 percent conclusive.
When suspicious lumps are found, doctors and patients will often opt for treatment ranging from surgery to radiation or chemotherapy, which can take months and cause serious side effects.
To better weed out patients who don't really need treatment, Thurber's team from the University of Michigan developed an oral pill containing an imaging agent that selectively binds to cancer cells or blood vessels that are unique to tumors. Once attached to its target, the dye fluoresces under near-infrared light. Although at this wavelength, fluorescent tumors can only be detected 1 to 2 centimeters deep, Thurber says given the elasticity of breast tissue, pairing his technique with ultrasound in the same instrument should be able to detect most cancers.
Testing in mice showed that with the proper formulation, a considerable proportion -- 50 to 60 percent -- of the agent gets absorbed into the bloodstream. It also binds specifically to cancer cells with little background noise in the image. That is, the fluorescent signal from the tumor was far stronger than the signal from the surrounding tissue.
If his team succeeds in formulating the pill for human patients, Thurber says the high image contrast should bode well for women with dense breast tissue whose mammograms are difficult to read. Additionally, Thurber is designing the agent to specifically seek out aggressive tumors, an approach that could distinguish them from slow-growing cancers such as ductal carcinoma in situ, a noninvasive breast cancer.
Now Thurber is coupling the probe with molecules to make it easier for human patients to absorb. Predicting when his agent might go into human clinical trials is difficult, he says. However, the dye is already used in Europe for other clinical applications, which could help speed the approval process in the U.S.
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A press conference on this topic will be held Tuesday, March 15, at 2 p.m. Pacific time in the San Diego Convention Center. Reporters may check-in at Room 16B (Mezzanine) in person, or watch live on YouTube http://bit.ly/ACSliveSanDiego. To ask questions online, sign in with a Google account.
Thurber acknowledges funding from the National Institutes of Health and the University of Michigan.
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Title
Disease Screening Pill for Breast Cancer: In Vivo Demonstration of an Orally Available Near-Infrared Molecular Imaging Agent Using Mouse Xenografts
Abstract
Some of the most significant advances in disease treatment come from early detection and therapy. Minimally invasive blood tests and non-invasive imaging are two of the most widely used methods for screening patients, but improved methods would reduce morbidity and mortality for many diseases. Blood tests generate extensive molecular information, but the nature of the test loses all spatial information within the body. Imaging techniques yield accurate spatial information but often only provide anatomical results or require high cost and/or ionizing radiation for molecular imaging. We report the development of an orally available near infrared molecular imaging agent that can be delivered and detected in a needle-free completely non-invasive manner with no ionizing radiation. A series of probes with varying physicochemical and optical properties was tested to determine the required balance of molecular imaging agent properties. The use of a permeability enhancer to transiently loosen tight junctions and an ion-pairing agent to shield the negative charge of the cyanine fluorescent dye increased bioavailability over an order of magnitude and allowed efficient uptake of a highly specific targeted probe. By selecting an agent with the proper balance of oral bioavailability, specific tumor targeting, and ideal optical properties, we demonstrated whole animal target to background ratios of 4.7 and tumor to muscle ratios over 20 following oral gavage in an orthotopic breast cancer mouse model. These results can be used to optimize molecular imaging agents and design new probes for orally available near-infrared non-invasive disease screening.