Three new radiotracers now available for clinical use at Mallinckrodt Institute of Radiology are revolutionizing the way certain cancers are detected and ultimately treated. When paired with a PET/CT scanner, the new tracers — C-11 choline, F-18-fluciclovine (FACBC) and Ga-68 dotatate — provide essential information previously unattainable.
According to Richard L. Wahl, MD, director of MIR and head of the Department of Radiology, the new oncologic PET examinations are highly sensitive. “It’s about knowing if there’s cancer, where it’s located, if it’s localized or disseminated, and then using that information to more precisely inform and guide treatment,” says Wahl. “We’re talking about precision cancer imaging.”
Early Detection for Prostate Cancer
C-11 choline and FACBC are used to detect suspected, biochemically recurrent prostate cancer as indicated by rising PSA levels after prior treatment. Of the two radiopharmaceuticals, C-11 choline is produced on site at MIR.
“We’re one of a handful of institutions across the nation with FDA (U.S. Food and Drug Administration) approval to manufacture C-11 choline,” says Barry Siegel, MD, professor of radiology and of medicine, Senior Vice Chair and director of the MIR’s Division of Nuclear Medicine.
Access to C-11 choline is limited to facilities that have an on-site cyclotron and FDA approval to produce the radiopharmaceutical. MIR has four cyclotrons in use.
“The application is expensive, the approval process is stringent, and the tracer is short lived,” Siegel says. C-11 choline loses half of its radioactivity every 20 minutes. Because it decays so quickly it must be produced on site, he adds.
C-11 choline PET is so sensitive it can detect tiny pockets of cancer before a tumor becomes visible through conventional imaging. Men diagnosed with a biochemical recurrence at this early stage have more options for curative treatment.
Both oncologic tracers are used with a PET scanner, which tracks the localization of the radiopharmaceutical throughout the body. Because cancer cells accumulate the C-11 choline or FACBC, the increased uptake appears as “hotspots” on the scan.
“Of all the men who have curative therapy for prostate cancer, at least 30% of them will experience biochemically recurrent disease,” Siegel says.
Not only can the exam detect if there is a recurrence of prostate cancer, it can pinpoint the exact location of the relapse. However, a biopsy is still typically needed to confirm cancer.
Although the molecular mechanism behind each radiopharmaceutical is different, C-11 choline PET and FACBC PET exams have largely similar detection rates. FACBC has a longer half-life (110 minutes) but is made offsite and is currently available at MIR once a week. C-11 choline is offered five days a week.
Candidates for C-11 Choline & FACBC
“In general, we’re selecting men whose bone scans and CT/MRI scans are either negative or equivocal (non-informative) for disease,” says Siegel, “then using the new PET studies to define the active disease and its location so the referring physician can make a treatment decision.”
While the purpose of either scan is to map out the full extent of the disease, the broader goal is to see if a cure can be achieved without resorting to systemic therapy, which has multiple side effects and usually leads to the tumor ultimately becoming resistant to treatment.
How Low Can You Go?
Mallinckrodt will consider imaging patients with PSAs as low as 0.2 after a prostatectomy, Siegel says. But the scans perform better with men who have higher levels, he adds.
Ralph Erickson, 72, from Kirkwood, MO, has had two relapses. He’s also had C-11 choline and FACBC PET examinations. The former test was performed in 2013 at the Mayo Clinic in Rochester, MN, (the only site at the time with C-11 choline) and the latter at Mallinckrodt in 2017. Both exams found a cancerous lymph node.
“PSA level is a surrogate for how much tumor volume is likely to be present. Therefore, the sensitivity of the tracers increases as the PSA level increases,” Siegel says. Erickson’s PSA levels reached 1.7 ng/mL when his C-11 choline PET exam was performed, and 1.3 ng/mL when his FACBC PET exam was performed. Both detected early stage cancer.
In the past, patients like Erickson would have been followed until their PSAs were higher. But the game is changing, says Siegel.
Finding the NETs
Ga-68 dotatate, the third new oncologic PET tracer, is used for localizing neuroendocrine tumors, or NETs, expressing somatostatin receptors (SSTRs) in adults and children. Made daily at Mallinckrodt, the tracer is dramatically changing how these tumors are found.
NETs develop in the hormone-producing cells of the body’s neuroendocrine system and most often occur in the lungs, appendix, small intestine and pancreas. According to Farrokh Dehdashti, MD, a professor of radiology in the Division of Nuclear Medicine, they are rare and “very difficult to detect.”
Left: Reproduction image of Ga-68 dotatate PET with multiple meta static foci
Conventional imaging with computed tomography (CT) and magnetic resonance imaging (MRI) scans often miss them, and the imaging agent (indium-111 pentetreotide or Octreoscan) that’s been used for years to detect NETs has a low detection rate.
NETs have receptors for somatostatin, a hormone that regulates the endocrine system. Ga-68 dotatate works by binding to these receptors, which sit on the surface of cancerous cells. The result is superior images and vastly better detection.
Better, Faster, Costs the Same
“Ga-68 dotatate is a huge improvement in our ability to diagnose and detect the presence and extent of neuroendocrine disease,” Dehdashti says. “With this agent, we see so many very small lesions, even those you wouldn’t consider as disease by conventional imaging.”
Information from the exams also helps with selecting the most appropriate therapy, as well as with follow-up evaluation of that therapy. In addition to being far more effective than the previous standard diagnostic agent, imaging with Ga-68 dotatate is also quicker than that with indium-111 pentetreotide. The latter is performed over a two-day period with an injection on day one and a scan on day two. With Ga-68 dotatate PET, patients are scanned in a single session lasting less than two hours. And it turns out Ga-68 dotatate doesn’t cost any more, says Wahl.
The Next Best Thing
Nuclear imaging is evolving at a rapid clip with new tracers replacing older ones all the time. The ability to make the oncologic radiopharmaceuticals on-site is increasingly important, especially for those tracers
with shorter half-lives.
Above: Barry Siegel, MD, with Farrokh Dehdashti, MD, in front of a PET sacnner at the Center for Clinical Imaging Research.
“We have a state-of-the-art cyclotron, and state-of-the art radiopharmacy and radiochemistry facilities that allow us to manufacture radiopharmaceuticals that are patient-grade,” Wahl says.
But having world-class facilities is not enough. You have to know how to interpret information provided from advanced imaging techniques, he adds. And in order to do that, “you need to have enough volume so you become expert at reading them.”
C-11 choline, FACBC and Ga-68 dotatate with PET/CT and PET/MRI are approved by the U.S. Food and Drug Administration for clinical use and covered by Medicare for the aforementioned indications. All tests can be ordered via Allscripts or by calling (314) 362-8275.