UCSF and Berkeley Lab researchers have demonstrated a new way of using standard positron emission tomography scanners to track radioactive cancer therapies in a patient, overcoming a long-standing limitation of the technology.
This advance could eventually allow clinicians to more precisely monitor targeted therapies as they move through the body and make treatment decisions based on how the drug is distributed.
“I had this idea a few years ago, and the biggest challenge was to find the industry support and the equipment necessary to realize our proof of concept,” said Lawrence Berkeley National Laboratory scientist Javier Caravaca, who worked on the research, in an email. “We collaborated with SIEMENS Healthineers US, which was extremely helpful in giving us access to their scanner as a research tool.”
Targeted alpha therapy is a type of cancer treatment in which targeting molecules, called radiopharmaceuticals, deliver radioactive atoms, called alpha emitters, directly to cancer cells. These molecules deliver atoms that release ionizing radiation, which is fatal to cancer cells, while ideally limiting damage to surrounding healthy tissue.
However, in practice, some of the radiopharmaceuticals in targeted alpha therapy can also collect in healthy organs, and radioactive atoms can detach from the targeting molecules and accumulate elsewhere in the body. Because of this risk, being able to visualize where the treatment is going and how much is reaching different parts of the body proves vital for monitoring its effectiveness and safety.
Thus, the challenge facing researchers is to find a way to image these therapies. Positron emission tomography is one of the most efficient and precise imaging modalities, but conventional PET scanners are designed to detect a specific type of subatomic particle called positrons.
Targeted alpha therapies, which in this study uses actinium-225, or Ac-225, do not typically produce positrons, according to Caravaca. As a result, conventional PET cannot directly track where the treatment is distributed in the body.
To overcome the problems around tracking these therapies, the research team developed a new approach called time-of-flight cascade gamma-ray imaging, or TOF-CGI. Rather than detecting positrons, the technique uses gamma rays produced during the rapid decay of Ac-225’s daughter isotope, thallium-209.
These gamma rays are released in a rapid cascade. Measuring the time and location of these gamma rays enables researchers to construct a 3D image showing where the Ac-225-related emissions wound up in the body.
The researchers conducted a pilot imaging study using a single prostate cancer patient. Using a commercial PET scanner, the team could produce an image of the Ac-225-related emissions in the patient.
This new technique could help monitor patients over the dayslong period of treatment that these radiopharmaceutical therapies require.
“Thanks to this, clinicians could make decisions based on imaging that wasn’t possible before, such as, stopping, continuing or changing treatment based on how the drug is distributing in the body,” Caravaca said in the email.
The pilot study was conducted with a single patient, but the team expects to image more patients in the near future. According to Caravaca, the technique could also extend to any cancer treatment modality using Ac-225 or other similar alpha emitters.