For patients who have undergone radiation treatment for brain metastases, finding a new abnormality on MRI does not always provide a clear answer about what is happening. Radiation itself can produce changes in brain tissue that resemble tumor progression, creating a difficult clinical question at exactly the point when physicians need to know whether a patient’s cancer has returned.
Radiopharm Theranostics is developing F-18 RAD101 as a PET imaging agent for that problem. The company announced this week that interim Phase 2b results have been selected for a late-breaking oral presentation at the 2026 Society for Neuro-Oncology Annual Meeting, adding another step toward a planned Phase 3 registrational program. The underlying Phase 2b results were initially reported in July, when Radiopharm said RAD101 met the trial’s primary endpoint.
RAD101 is a fluorine-18-labeled small molecule designed to target fatty acid synthase-related tumor metabolism. The Phase 2b study enrolled 30 patients at five U.S. centers who had previously received radiation for brain metastases and were suspected of having recurrent disease. Across evaluable lesions, RAD101 PET demonstrated 93% concordance with MRI, while preliminary follow-up and biopsy data from 14 patients produced sensitivity of 86%, or 12 of 14 patients. Specificity data are expected later in 2026.
MRI remains the central imaging tool for patients with brain metastases, but radiation can complicate interpretation. Treatment-related tissue injury can produce enhancement and other changes that resemble active tumor, while recurrent disease can appear similar on conventional imaging.
The distinction matters because the next steps can be very different. A patient with active recurrent cancer may need additional systemic therapy, surgery, radiation or another intervention, while treatment-related changes may call for observation or management of radiation injury rather than another cancer-directed treatment.
Radiopharm is positioning RAD101 as a complementary molecular imaging tool that could provide additional biological information when structural imaging leaves uncertainty. Rather than replacing MRI, the commercial opportunity would be to add a second layer of information in cases where physicians need greater confidence about whether a suspicious lesion represents viable tumor.
That is a familiar pattern in nuclear medicine. PET has historically been most valuable when it can answer a biological question that conventional anatomical imaging cannot answer reliably on its own.
Radiopharm now plans to move RAD101 into a multicenter, multinational Phase 3 registrational trial, with an FDA meeting scheduled for Oct. 1 to align on the pivotal study design. The company previously said it expects to initiate the Phase 3 program in the fourth quarter of 2026.
That transition is significant because RAD101 is currently Radiopharm’s most advanced diagnostic program. The company has received FDA Fast Track Designation for the agent and has also established a manufacturing and distribution relationship with Siemens Healthineers to support the Phase 3 trial with F-18-labeled RAD101 doses.
Using fluorine-18 gives the program a different commercial profile from tracers dependent on shorter-lived isotopes or generator-based production. F-18 can be manufactured at regional cyclotron facilities and distributed through established PET radiopharmacy networks, a model already used at scale for other molecular imaging products.
Radiopharm has estimated the imaging market for brain metastases at more than $600 million and has emphasized that there is currently no FDA-approved PET product specifically for this use. That estimate comes from the company, but the lack of an approved PET agent for the indication helps explain why Radiopharm sees an opportunity beyond simply developing another oncology tracer.
Brain metastases are considerably more common than primary brain tumors and can develop in patients with cancers including lung, breast and melanoma. Improvements in systemic cancer therapy have also allowed more patients to live long enough for brain metastases to become an increasingly important part of long-term cancer management.
That creates a difficult follow-up problem. As more patients undergo stereotactic radiosurgery and other radiation treatments, clinicians are increasingly confronted with post-treatment imaging abnormalities that can be difficult to characterize with certainty.
A molecular imaging agent that helps distinguish recurrence from radiation-related changes could therefore fit into a growing clinical workflow rather than requiring physicians to adopt an entirely new treatment paradigm. The practical question for RAD101 will be whether the Phase 3 program can show enough diagnostic accuracy and clinical utility to justify adding PET to that workflow.
Radiopharm has built a pipeline spanning both imaging and therapy, including Lu-177 programs targeting PD-L1 and HER2, a B7-H3-targeted radiotherapeutic being developed through its collaboration with MD Anderson Cancer Center, a terbium-161 prostate cancer program and the Ga-68 RAD301 imaging agent targeting integrin αvβ6 in pancreatic cancer.
RAD101 is different from many of those programs because it is not directly tied to a therapeutic counterpart. Its value proposition is instead based on solving a diagnostic problem that emerges after another therapy has already been delivered.
That makes its development a useful reminder that the growth of nuclear medicine is not limited to theranostics. Some of the field’s largest opportunities may come from using PET to resolve questions created by increasingly sophisticated cancer treatments, particularly when conventional imaging cannot confidently distinguish disease from the biological effects of treatment.
The next major test for RAD101 will come after the Oct. 1 FDA meeting, when Radiopharm expects to finalize the path into Phase 3. If the pivotal study confirms the Phase 2b findings, the company could eventually have a PET product aimed not at finding brain metastases for the first time, but at answering the question that comes later: after radiation has changed the image, is the cancer actually back?
