The Next Blockbusters
Take Apomate, a molecular-imaging agent made by Boston, MA-based Theseus Imaging (a subsidiary of North American Scientific) that gives physicians a novel view of a biological drama that plays out in the body all the time. The complex chain of events that leads to a cell’s death, a process that biologists call apoptosis, is central to everything from embryonic development to aging; Apomate allows researchers to directly observe these events. By imaging cells’ death throes, doctors might be able to see if a particular chemotherapy is successfully killing tumor cells, say, or more accurately assess damage caused by a heart attack.Like many of the other new imaging agents in development, Apomate draws on the recent explosion in biologists’ understanding of the details of the body’s molecular processes. Among other findings, scientists have begun to unravel the precise details of apoptosis. It turns out that dying cells expose a binding site that’s normally concealed. A naturally occurring protein then binds to that site, marking the cells for destruction by the immune system. Theseus created Apomate by engineering a synthetic version of the protein and linking it to a radioactive isotope that shows up under a scanner. When a patient is injected with Apomate, areas of the body where many cells are dying light up.
Apomate’s potential market is large because of the myriad roles apoptosis plays in the body and the many ways doctors could use the agent. In human trials-ongoing in Europe now and likely to begin shortly in the United States-doctors are giving Apomate to lung cancer patients shortly after their first injections of chemotherapy. The aim is to determine within a day or two of the injections whether the drug is actually killing tumor cells. Patients who aren’t helped by a particular chemotherapy drug can then be spared the wasted time and often debilitating side effects of the treatment-and can more quickly move on to explore other options. “Only 20 percent of these patients respond to the therapies, but 90 percent have side effects,” explains Allan M. Green, chief technology officer at North American Scientific and Theseus. “To recognize early responses patient by patient is the most important near-term contribution we can make.”
Theseus has also tested Apomate in more than 50 heart attack patients. Green says investigators have discovered a small subset of patients in whom apoptosis continues to take place in heart tissue even months after an attack. And researchers suspect these patients may be the most likely candidates for subsequent heart failure. If Apomate could help identify these patients, whose heart cells are continuing to die off, it could provide valuable clues as to who should be treated most aggressively-before their hearts begin to fail.
Researchers have also been using Apomate to try and identify unstable plaques in coronary blood vessels. It appears that the plaques most likely to rupture and cause heart attacks demonstrate a measurable amount of apoptosis as they crack and chip. If this work on imaging vulnerable plaques pays off, it could help doctors identify ahead of time some of the hundreds of thousands of people each year whose first indications of heart disease might otherwise be lethal heart attacks.
Doctors currently have ways of looking at structural changes in coronary arteries, but to find earlier danger signs “you need to know the biology,” says Stanford University radiologist Francis G. Blankenberg, a consultant to Theseus. Blankenberg says he envisions imaging schemes that look for apoptosis becoming part of a standard battery of tests for patients showing any kind of chest pain.