Drug Delivers Longer-Lasting Isotopes to Tumors

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In the movies, Lex Luthor was always scheming to bring Superman within reach of Kryptonite's deadly radiation¿the closer to the hero, the better. If only Lex had what researchers now do: a way of treating each cell in a tumor to its very own radioactive atom for days on end, from the inside. This molecule-sized delivery system, crafted by a team at the Memorial Sloan-Kettering Cancer Center in New York, could make radiation therapy for a wide variety of cancers safer for patients, who suffer side effects when the killing rays invariably overshoot their cancerous mark and damage healthy tissues. A report published today in the journal Science describes the first results in mice of these so-called nanogenerators.

Senior author David Scheinberg first targeted radioactive molecules to tumors 20 years ago. But despite recent successes, the 45-minute half-life of the most often used element limited application of this technique to certain cancers. So the researchers turned to actinium-225, which decays by half every 10 days and, along with the series of isotopes it generates, fires off short-range, high energy rays called alpha particles capable of devastating cancer cells in close proximity. To accomplish this trick, the team caged actinium atoms inside rings of carbon and attached them to antibodies that specifically recognize cancer cells. This setup allowed each isotope to burrow straight to the heart of its target and destroy a cell from within. "These are extraordinarily potent drugs. One atom will kill a cell," Scheinberg says.

Tiny doses of nanogenerators built from different antibodies were able to kill a range of human cancer cells in the laboratory, including leukemia, lymphoma, breast, prostate and ovarian. In experiments on mice with prostate cancer and lymphoma, they kept nearly half of both groups of animals alive for 300 days. Left untreated, the rodents all died within two to three months. Human trials could begin as early as next year, Scheinberg says. Actinium's long half-life, he adds, should make it effective against large tumors and easy to distribute widely.

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