Scientists in the Departments of Radiation Oncology and Medicine at the University of Washington (UW) and Fred Hutchinson Cancer Center (Fred Hutch) are directly targeting cancerous cells traveling through patients’ bloodstreams with diseases such as leukemia and lymphoma using an intravenous injection of the radioactive isotope astatine-211 (At-211). The work, its challenges, and its promise were described in a recent news release from the National Isotope Development Center (NIDC), which is managed by the Department of Energy’s Isotope Program.
According to the NIDC, early results of clinical trials with over 40 cancer patients at Fred Hutch suggest that At-211, with a 7.2-hour half-life, can deliver sufficient radiation therapy to patients with blood-borne cancers while minimizing exposure to the rest of the body and to health care teams. The team at UW is now developing an automated production process to share with other research facilities. The DOE’s University Isotope Network, of which the UW Medical Cyclotron Facility is part, is planning to integrate production sites to deliver short-lived isotopes to more medical facilities and patients across the United States.
Novel approach: Scientists at UW can produce At-211 at UW’s Medical Cyclotron Facility and deliver the treatment just hours later to Fred Hutch in what the organizations call a “bench-to-bedside” approach.
As an alpha emitter, At-211 releases just one alpha particle per decay and decays away to just 10 percent in 24 hours, rather than days or weeks for traditional beta emitters and some other alpha emitters. When combined with a biological targeting agent, such as a monoclonal antibody, capable of latching on to a cancerous cell in the bloodstream, that alpha particle can kill the targeted cell.
According to UW and Fred Hutch, the clinical trials now underway mark the first time At-211 has been injected intravenously to attack blood-borne cancers such as leukemia, lymphoma, myelodysplasia, or myeloma.
“We’re looking for a new way to treat blood-borne cancers that one day may eliminate the need for total body irradiation, so we only minimally expose healthy tissues to radiation,” said Scott Wilbur, professor and researcher in the Department of Radiation Oncology at UW, who has worked with At-211 for several years.
The process—at the cyclotron: To deliver doses of At-211 to patients in the afternoon, scientists must begin producing At-211 in the cyclotron at midnight, bombarding a bismuth target with alpha particles from a helium source for six to seven hours. Up to 130 millicuries of At-211 are required to produce a dose of At-211.
Robert Emery is director of the technical support group of the UW Medical Cyclotron Facility, which is the world’s leading producer of At-211. According to the NIDC, Emery and his team must keep the alpha beam stable through the night by continually adjusting the gas pressure and voltage of the helium source, in a process Emery likens to the give-and-take of adjusting the antenna on an old TV set to maintain a good signal.
The process—in the lab: For the next five hours, beginning at about 7 a.m., the newly produced At-211 is isolated, certified, and attached to the antibody in a sterile environment using a “wet chemistry” labeling technique.
Wilbur developed an antibody labeling process using a decaborate molecule with a cage-like structure to improve labeling speed and efficiency and significantly strengthen the At-211 bond, according to the NIDC. The labeling process is important to ensure the radioisotope does not separate from the antibody inside the patient and impact healthy parts of the body.
Benefits: UW and Fred Hutch researchers and clinicians believe that targeted alpha therapy (TAT) is particularly good at finding and targeting metastasized cells early and can eliminate them before they grow and harm to the tissues they invade. In one clinical trial, the use of At-211 has shown the potential to decrease disease levels to the point where patients become eligible for bone marrow transplants, according to the NIDC.
“If the gold standard of radiation therapy is to do maximum damage to cancer cells without damaging other healthy cells, then TAT is that just-right mix—the smart bomb of radiation therapy,” said Emery.