New contrast agent guides breast cancer surgery
Mammography is the current gold standard for detecting breast cancer, but it is limited by its relatively low sensitivity and specificity. Investigators therefore have devoted considerable effort to developing alternative techniques that address these drawbacks. In the Oct. 22 issue of Angewandte Chemie International, researchers with Beth Israel Deaconess Medical Center/Harvard Medical School in Boston reported a technique that takes advantage of microcalcifications that result from the deposition of calcium salts in breast tissue. Using a simplified, reproducible synthesis strategy, they developed a near-infrared fluorescent optical contrast agent specific for hydroxyapatite, one of the more common forms of the salts.
Researchers have reported a near-infrared fluorescence optical contrast agent for the detection of breast cancer. The contrast agent takes advantage of microcalcifications resulting from the deposition of calcium salts in breast tissue. It also enables real-time near-infrared fluorescence imaging of normal bones during surgery, as demonstrated in these images of bones in a 30-kg Yorkshire pig. Images courtesy of Barbara L. Clough.
The investigators characterized the agent, named Pam800, by confirming that its maximum absorption and emission (778 nm and 799 nm, respectively) fell within the “near-infrared window” — the region of the spectrum most conducive to near-infrared measurements — and by showing that it has more than eightfold specificity for hydroxyapatite with respect to other calcium salts, thus allowing high-sensitivity near-infrared fluorescence detection of the target compound.
They sought to validate its in vivo performance during image-guided surgery. They used 30-kg Yorkshire pigs, whose organs are approximately the same size as those of humans.
After administering the Pam800, they performed image-guided surgery using a custom intraoperative near-infrared fluorescence imaging system. An array of 10 1-W LEDs made by Marubeni Epitex of New York provided near-infrared excitation, while an array of four white LEDs made by Philips Lumileds Lighting Co. of San Jose, Calif., provided white light; all of the near-infrared wavelengths were filtered out of the latter. A dichroic mirror deflected the visible light (400 to 700 nm) to a color videocamera made by IMI Technology Co. of Seoul, South Korea. After traveling through a long-wave pass filter, the near-infrared fluorescence (>785 nm) was sent to a near-infrared-sensitive camera made by Hamamatsu of Bridgewater, N.J.
The researchers had injected the pigs with hydroxyapatite and calcium oxalate crystals to mimic the microcalcifications that would be found during breast cancer surgery — calcium oxalate typically is found in benign lesions but rarely in malignancies. They noted that the contrast agent detected the former but not the latter and thus could guide surgeons in identifying malignancies in the breast.
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