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St. Jude creates powerful tracer molecules to hasten our understanding of childhood cancers.
Early on a misty morning, 11-year-old Latrevious Moore arrives at St. Jude Children’s Research Hospital for a test that is an essential part of his cancer therapy. As the procedure begins, the sleepy sixth-grader listens to a favorite radio station and anticipates the upcoming day’s activities—breakfast, followed by a clinic appointment and an enjoyable afternoon of playing video games.
Latrevious undergoes positron emission tomography (PET) scans as part of his treatment for Hodgkin lymphoma, a cancer of the immune system that can affect the lymph nodes, bone marrow, spleen and other internal organs. Before dawn broke this morning, scientists in a basement laboratory were racing to produce the radioactive drug that now moves through Latrevious’ body.
The radioactive chemicals used in that drug are created in a powerful machine called a cyclotron, or a particle accelerator. The St. Jude cyclotron is the only one of its kind solely dedicated to producing radioactive “tracer molecules” for pediatric treatment and research.
PET scanning is an extremely sensitive imaging technology that can measure biological processes as they occur in real time. Scientists start with a compound normally used by the body—such as glucose, water or ammonia—and tag it with a radioactive atom called an isotope. A technologist then injects a small amount of that material into the patient. Clinicians use the PET scanner to track the movement of the tagged molecule, or tracer, as it travels through the body. With this special camera, they can diagnose illnesses, measure blood flow, monitor tumor growth and track the progress of therapy.
“PET scanning is what we call functional imaging,” explains Barry Shulkin, MD, chief of Nuclear Medicine. “It not only tells you what something looks like, but more importantly, it tells you what it is doing. MRI and CT are principally anatomic imaging; they tell you what something looks like—but not always what it is doing.”
The challenge of using PET is that the radioactive isotopes used have short lifespans. Only one PET drug is commercially available—a tracer called fluorodeoxyglucose, or FDG. This drug has a two-hour half life, which means that half of its radioactivity dissipates every two hours. Most hospitals obtain FDG from local producers, who deliver the drug as soon as it has been produced. Other PET imaging drugs have half-lives of only 10 to 20 minutes, so they must be produced at the facility where they will be used. Several years ago, St. Jude clinicians and researchers realized that these drugs would help them accelerate the treatment and research of childhood cancer. As a result, in 2008 St. Jude obtained the most powerful medical cyclotron available—the first one of its kind installed in the United States.
The ability to create radiopharmaceuticals has enabled St. Jude researchers to pursue new areas of investigation that have exciting implications for children with cancer. Several days each week, scientists in the Molecular Imaging Research laboratories produce carbon-11 (C-11) methionine, a drug with a half-life of 20 minutes. Methionine is a type of amino acid, a building block of proteins. Because tumor cells grow rapidly, they create many new proteins. “Using carbon-11 methionine, you can measure how fast the tumor is making new proteins or making new components for the cell,” says Scott Snyder, PhD, director of Molecular Imaging Research. “The advantage of methionine is that it only accumulates in tissues that are actively producing new tissue.”
When compared with FDG, the drug C-11 methionine is much better suited for brain imaging. The brain and its tumor both absorb FDG, so brain tumors are not easily visible in scans created using that drug.
“If you use fluorodeoxyglucose in the brain, it’s kind of like seeing the stars when the sun is out,” Shulkin says. “The stars are there, but you can’t see them, because there is so much light in the background.”
On the other hand, tumors absorb C-11 methionine but the surrounding brain does not take up that drug; thus, scans created using C-11 methionine provide clearer images. Shulkin and his colleagues are also using C-11 methionine on other kinds of tumors to determine whether that drug can provide new information as well as predict the outcome of therapy.
C-11 methionine has a long lifespan when compared with N-13 ammonia, a radiopharmaceutical that has a half-life of only 10 minutes. This drug can be used to measure blood flow in the heart.
“Eventually we want to help evaluate some long-term survivors of childhood cancer and determine their risk for coronary disease,” Shulkin says. “We’re also interested in looking at patients who have more recently had therapy to determine very early whose hearts may have been affected by therapy. If we can identify people who are at risk, then we can help doctors determine whether an intervention—say, medicine or exercise—could help prevent that possible side effect.”
Two upcoming studies using radiopharmaceuticals may also hold promise for children with neuroblastoma. Shulkin is collaborating with chemists at the National Institutes of Health to test a radioactive drug called fluorodopamine for use in
children with neuroblastoma.
“We believe that neuroblastomas will have excellent uptake of this drug,” he observes.
Another project involves the neuroblastoma antibody that is currently in production at St. Jude.
“What we want to do is to attach a little bit of radioactivity to that antibody to tell us where the cells are and whether the treatment has a likelihood of success in a patient,” Shulkin explains.
Someday, doctors may use a drug called C-11 acetate to monitor how well children like Latrevious Moore are responding to therapy. Typically, clinicians measure tumors, administer treatment and then measure the tumors again in six months or so. But Snyder predicts that C-11 acetate may help change that scenario.
“We might be able to tell as little as a few days after the therapy whether or not the treatment is actually working,” he says. “Instead of going through three six-week courses of chemotherapy, a patient might be able to go through the first six weeks, take a week or two off and get this scan to tell whether the chemo is working. If it has worked very well, then the child might not have to go the entire 18 weeks of doses; if it has not worked, then we will know early on that we should try something else.”
Latrevious is not interested in the latest radiopharmaceutical drugs or the science behind PET scanning. He is much more intrigued with the possibility of learning the saxophone, planning his birthday and mastering his latest video game.
“They do PET scans to see if my chemo’s working,” he says matter-of-factly, as he rewinds the string on his yo-yo.
For Latrevious, that’s the bottom line: PET scanning gives doctors information that will save his life—and make all of his plans possible.
Birth of a PET drug
Reprinted from Promise Summer 2010