Zhen Cheng, assistant professor of radiology and a member of the Molecular Imaging Program at Stanford University, says that he is impressed by the specificity of Frangioni’s agent for hydroxyapatite: the agent binds to the molecule but not to other calcium-containing compounds. Frangioni has tested the agent in bones and soft tissue in pigs but has not done tests in a breast-cancer model. “The in vivo images [he] acquired are quite impressive,” says Cheng. The Harvard group’s next goal is to validate its work in human clinical trials.
Other researchers and oncologists are skeptical of the usefulness of the hydroxyapatite-targeting agent. “In theory, it sounds like an interesting idea,” says Elizabeth Steiner, assistant professor of family medicine at the Oregon Health and Sciences University. “But you can have benign calcifications.” That is, the presence or absence of hydroxyapatite is not enough to distinguish between cancerous and healthy breast tissue.
But the imaging researchers say that detecting cancer at the molecular level does not depend on the total absence of the targeted molecule from healthy tissue. Tromberg points to the example of herceptin, a drug that targets cell receptors present in normal tissue as well as breast-cancer tissue. “All the normal cells have it, but maybe there’s 10 percent more on tumor cells,” he says. A 10 percent difference in the levels of hydroxyapatite in cancerous and normal breast tissue would be more than enough to provide imaging contrast, he says.
However, Tromberg acknowledges that the technology faces many hurdles. It’s unlikely that patients will accept fluorescent dyes as a part of routine screening. “From a practical point of view, people don’t want to be injected with probes to do screening,” he says. The agents may be more tolerable to some groups of patients, such as women at high risk for breast cancer who are considered too young for mammography. The agents could also be used as follow-up testing for patients with suspicious mammograms or magnetic resonance imaging scans.
“The bottom line is, mammography is not a great test,” says Steiner, and any improvement in breast-cancer screening would be welcome.