Custom Molecule Enhances Radiation Therapy

PHILADELPHIA--A molecule known for its Texas-sized girth now appears to be a promising new weapon against cancer. A pilot trial of the new heavy metal-bearing compound, described here Saturday at the annual meeting of the American Association for the Advancement of Science (which publishes ScienceNOW), has extended the lives of people with brain cancer.

Natural pigments called porphyrins, which ferry iron in the blood, home in on tumors. Jonathan Sessler, a chemist at the University of Texas, Austin, thought that porphyrins might become couriers for anticancer drugs. Because Sessler says everything is bigger in Texas, he first wedged a fifth link into the porphyrin molecule, which resembles a bracelet of four linked rings. This new "Texas-sized" molecule--suitably dubbed texaphyrin--had a 20% larger capacity, enough to carry an atom of the heavy metal gadolinium. The gadolinium's net positive charge would be able to absorb excess electrons, which tend to recombine with hydroxyl radicals--corrosive molecules formed during radiation therapy against a tumor--and eliminate their cancer-killing effects. Gadolinium, Sessler hoped, would prolong the hydroxyl radical's effects and therefore increase the potency of radiation therapy.

To see if texaphyrins gravitate to tumors just as their porphyrin cousins do, Sessler used magnetic resonance imaging (MRI) to scan cancerous mice before and after a texaphyrin injection. Gadolinium shows up strongly in MRI. Sessler and colleagues at Pharmacyclics in Sunnyvale, California, found that cancer cells appeared as bright white regions on MRI scans even several days after a texaphyrin injection. When the team irradiated these mice, the tumor cells decreased or disappeared and 50% of the mice survived the 140-day study. Only 10% of mice irradiated without texaphyrins survived.

In early clinical trials, Sessler and his colleagues treated 39 metastatic brain tumor patients with texaphyrins 2 hours before radiation therapy for 10 days. The patients, who had a life expectancy of 2 to 4 months, survived an average of 188 days. The patients in the highest dose group survived an average of 362 days. Although studies of the drug are not complete, Sessler says, "there are people alive who would ordinarily be dead." The National Cancer Institute has chosen texaphyrins as part of its NCI decision network--a group of what it considers to be the most promising up-and-coming therapies.