Berkeley Lab's R&D 100-winning scanner could let doctors see where alpha-particle cancer drugs go

For years, doctors prescribing one of the most promising new classes of targeted cancer therapy have had to take it on faith. The drugs fire alpha particles directly at tumors, but the moment they enter a patient, the radiation becomes largely invisible to the scanners clinicians normally use to confirm a treatment is working. That blind spot has shaped how nuclear oncologists plan dosing, schedule follow-up, and explain risk.

That may be changing. A team at Lawrence Berkeley National Laboratory (Berkeley Lab), a U.S. Department of Energy research facility, has built a scanner that can image the faint gamma ray cascade left behind as alpha-emitting drugs decay inside a patient. The technology, called Time-of-Flight Cascade Gamma-ray Imaging (TOF-CGI), was named a 2026 R&D 100 Award winner on August 11, a recognition R&D Magazine presents each year to a hundred of the year's most disruptive new technologies.

Alpha-emitting drugs such as Actinium-225 work by hitching a radioactive payload to a molecule that hunts for a specific tumor marker. Once bound, the alpha particles shred the cancer cell's DNA over a range of only a few cell widths, sparing nearby healthy tissue. The biology is precise, and a growing pipeline of Ac-225 and Pb-212 therapies has produced striking early responses in prostate cancer, neuroendocrine tumors, and some leukemias. The problem is the diagnostic side. Traditional PET and SPECT scanners, the workhorses of nuclear medicine, struggle to image the high-energy gammas that Ac-225 emits in tiny amounts. Clinicians can give the drug, but they cannot easily see whether it reached the tumor, whether it landed in the right places, or how much of it ended up somewhere it should not.

TOF-CGI is designed to close that gap. Instead of trying to image a single gamma photon the way PET does, it looks at the cascade, the chain of gammas an alpha-emitting isotope emits in rapid succession as it decays. By measuring the timing of those emissions, the system can pinpoint where the decay happened without the heavy lead collimators SPECT relies on. The result, in principle, is a much more sensitive image of where the therapy actually went.

In a pilot study presented in June at the Society of Nuclear Medicine and Molecular Imaging annual meeting, the Berkeley Lab team ran the technique on a standard clinical time-of-flight PET scanner and reported a central sensitivity of 76.6 counts per second per megabecquerel, a measure of how well the scanner picks up faint signals, along with a markedly better signal-to-noise ratio than SPECT produces for the same isotope. The work was published as an abstract in the Journal of Nuclear Medicine's meeting supplement, and the underlying technology disclosure was filed through Berkeley Lab's intellectual property office in December 2025.

The pilot result is an abstract, not a full peer-reviewed clinical trial, and the team, led by Javier Caravaca Rodriguez at Berkeley Lab, is still working through the institutional technology disclosure process before any commercial path becomes concrete. Ac-225's broader supply chain, which has long been the binding constraint on alpha therapy, is a separate problem that TOF-CGI does not touch. And the lab's own framing, that the technology "paves the way" for advanced therapies, is the right register. It is a diagnostic step, not a clinical product.

What TOF-CGI has shown is a method that can run on scanners already installed in hospitals. That matters because the bottleneck for alpha therapy has not really been the drugs. The therapeutic isotopes, including Ac-225, Pb-212, and a growing list of next-generation candidates, have been improving for years. What has been missing is a way to plan treatment, verify delivery, and catch off-target exposure before it causes harm. If TOF-CGI holds up in larger studies, clinicians would gain a tool that today simply does not exist: a high-sensitivity way to watch an alpha-emitting therapy do its work, dose by dose.

The R&D 100 gala is scheduled for November 19 in Phoenix. The bigger question is what comes after: whether the cascade-imaging approach survives a full clinical trial, whether manufacturers can fold the technique into existing PET hardware, and whether the first patients to benefit will be the ones already enrolled in alpha-therapy studies, or the many more who might be, if clinicians can finally see what they are prescribing.