Reston, Va.-In a study to determine safe dosages of the isotope astatine-211 for treating patients with recurring brain tumors, researchers were pleasantly surprised to find that not only was the isotope's potency sufficient to kill residual cancer cells without damaging sensitive healthy brain cells, but the patients experienced longer survival rates.

"Astatine-211 has as much as five times or more cell-killing efficiency than the standard treatments of external beam radiation or beta-particle injection," said Michael R. Zalutsky, professor of radiology and biomedical engineering at Duke University Medical Center in Durham, N.C. The ability to deliver such a potent cancer killer without causing neurotoxicity (damage to the delicate neurological system that controls brain function) would be a tremendous step forward in combating this lethal disease, he said.

In the past, surgeons have been able to remove the tumor bulk, Zalutsky added, but were unable to see and thereby identify any residual cancerous cells that had escaped into the margins of the healthy tissue surrounding the tumor. It is these cells, however, that continue to grow into new tumors and eventually kill the patient. Scientists have long believed that radioimmunotherapy (RIT) could be the best way to destroy these cells, but demonstrating the feasibility of delivering a sufficiently potent radioactive isotope without harming healthy brain tissue has been heretofore impossible.
In this study, reported in the Journal of Nuclear Medicine, astatine-211 was chemically linked to the antibody 81C6, known to seek out and bind specifically to brain cancer cells. It was then administered to 18 patients with recurrent malignant brain tumors by injection into a surgically created cavity from which the visible tumor had been removed. Because alpha particles, such as those emitted by astatine-211, are large and more highly charged, compared to the much smaller and faster beta particles, they are able to travel to a depth of only two to three cells into the affected area, which is enough to deliver the fatal payload. Compared to other alpha emitters, astatine-211 has a relatively short lifespan (approximately 7 hours), which means that the radioactivity falls off rapidly and patients experience few if any side effects.

In this first study evaluating astatine-211 as a targeted radiotherapeutic agent in cancer patients, researchers were expecting to determine only dose-limiting toxicity (the amount of isotope necessary to destroy the cancer without killing healthy tissue). In addition, they discovered that many patients experienced an extended survival rate, ranging from an average of 52 weeks to 3 years (compared to 26 weeks for most recurrent brain tumor patients).

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