practice of the target.
A new infrared imaging contrast agent highlights hydroxyapetite (purple), a mineral usually associated with malignant breast cancer.
John V. Frangioni and Bhushan Kumar R.
CHICAGO, ILLINOIS - mammography is still the gold standard for early detection breast cancer, but it is far from perfect: the technique lacks up to 20% of breast cancers. Soon, he can get some help. The researchers reported here today at the annual meeting of the American Chemical Society that they have developed a pair of compounds that help locate the tiny mineral deposits build up, a characteristic of breast cancer. If the compounds prove safe and effective in humans, they could prove a boon to the fight against a disease that affects 1-8 women in the United States at some point in their lives.
With mammography, radiologists use x-rays to identify the strong and the tiny calcium deposits in breast tumors. These deposits, called microcalcifications, are common to both benign and malignant tumors. While the most common mineral in benign tumors is called calcium oxalate, another called hydroxyapetite is more common malignancies. Mammography can not distinguish the two. But researchers have known for years that a drug against osteoporosis called bisphosphonates can, as it binds to hydroxyapetite.
thereseveral years, the chemist John Frangioni and colleagues at Harvard Medical School in Boston, Massachusetts, began to connect different imaging molecules called bisphosphonate contrast agents in the hope that they could use the drug to target tumors with contrast agents. They hit on a called PAM800 which is a combination of the bisphosphonate and a fluorophore which emits infrared light. Initial tests showed the compound worked to highlight hydroxyapetite microcalcifications in mice. But researchers could not produce sufficient compound to continue their studies.
So, for their ongoing work, Bhushan Kumar, a postdoctoral assistant in the laboratory of Frangioni, returned to the drawing board and came up with a new scheme for the synthesis of large amounts of PAM800. This allowed researchers to study the compound in pigs. And animal studies reported today show that subcutaneous injections of PAM800 easily allowed them to highlight microcalcifications in animals.
team Frangioni also reported that they created another series of hydroxyapetite-spotting compounds that not only gives off an infrared signal, but also hosts a chemical group gadolinium giving a strong signal in MRI machines. Although researchers have not yet tested this compound in animal studies, Bhushan said they hope it will eventually give doctors a way to identify tumors with ultra-sensitivity infrared imaging combined with the ability of the MRI to pinpoint their location in three dimensions.
"This looks like a good approach," said Bimal Banik, a medicinal chemist at the University of Texas Pan American, Edinburg. Banik warns that neither of contrast agents has been tested yet on animals injected with cell lines of breast cancer, which he called an important step to take. But the early work is promising, he says, because it offers hope that physicians will soon be able to cancer breast image with several techniques simultaneously, which greatly increases the chances of identifying the disease in its early stages.
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