Early Phase 2b imaging readouts from the first three patients showed selective 18F-RAD101 uptake in brain metastases where MRI findings were equivocal, consistent with prior Phase 2a signals. The U.S. multicenter, single-arm study has reached 50% of its 30-patient enrollment target, with topline data expected in the first half of 2026.
Radiopharm Theranostics is advancing RAD101, a FASN-targeted PET tracer, in patients with brain metastases following radiotherapy, where distinguishing tumor recurrence from radiation necrosis remains a routine clinical impasse. The Phase 2b trial’s primary endpoint is concordance between 18F-RAD101–positive lesions and gadolinium-enhanced MRI, with secondary endpoints focused on accuracy, sensitivity, and specificity for identifying recurrence versus radiation necrosis in stereotactic radiosurgery–treated disease. The program holds an FDA Fast Track designation for differentiating recurrent disease from treatment effect, including in leptomeningeal involvement.
Strategically, the company is positioning a novel metabolic target to challenge the current imaging workflow in neuro-oncology, which leans on contrast MRI and, in select centers, amino-acid PET tracers. The choice to anchor the Phase 2b primary endpoint on concordance with MRI looks pragmatic rather than aspirational: it creates a regulatory bridge to existing standards while amassing the case mix needed to power a registrational design around diagnostic performance for recurrence versus necrosis. The signal from the first three Phase 2b patients is directionally supportive, but the pivotal hurdle is not uptake per se; it is establishing truth-standarded accuracy in a population where pathology is scarce and clinical adjudication is noisy. A global Phase 3 will depend on regulator alignment around reference standards and the extent to which the readout must demonstrate clinical utility beyond image quality.
Sites should anticipate operational lift around radiopharmacy logistics and standardization of image acquisition and central reads. The 18F label eases distribution compared to short-lived tracers yet will still require reliable regional production and tight scheduling against PET-CT or PET-MR capacity. For neuro-oncology and radiation oncology practices, a validated FASN PET signal could reduce diagnostic latency after SRS, potentially curbing unnecessary biopsies or steroid escalations. CROs supporting imaging trials will see familiar complexities: lesion-level adjudication, inter-reader agreement, and spectrum bias control across tumor origins and prior therapies. Payers and guideline bodies will look for more than concordance—change in management rates and downstream outcomes will influence adoption and reimbursement, particularly in the U.S., where new PET agents face heterogeneous coverage at launch.
The near-term watch items are straightforward. Completion of enrollment sets the stage for a dataset that must quantify sensitivity and specificity against a defensible truth model, ideally with a prospectively defined surgical or long-term follow-up subset. Inter-reader variability and performance in SRS-treated lesions and leptomeningeal disease will matter for label language and real-world utility. Any Phase 3 blueprint should clarify whether the aim is superiority over MRI in equivocal cases, non-inferiority with additive value, or a management-impact design. Commercial readiness—radiopharmacy partnerships, reader training, and alignment with RANO and NCCN-aligned workflows—will be as decisive as the statistics. If the Phase 2b accuracy metrics are compelling and regulators accept the reference framework, Radiopharm can move quickly under Fast Track; if not, the path could lengthen into additional, utility-focused studies before broad uptake.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
