RAD 101 Demonstrates Positive Results in Brain Metastases

Interim data from a phase 2b clinical trial (NCT06777433) show that the novel imaging agent for patients with brain metastases, RAD 101, reached the trial’s primary end point and demonstrated significant and selective tumor uptake.^1,2

The analysis of the first 12 patients of the trial showed that 92% (n = 11/12) achieved concordance with MRI imaging.

The results showed significant and selective uptake of the agent in brain metastases, confirming metabolic activity. This is particularly valuable in cases with equivocal MRI findings.

“These compelling interim data significantly strengthen confidence in the success of our [p]hase [2] trial of RAD 101 and provide a strong foundation for initiating a pivotal study by the end of 2026,” said Riccardo Canevari, CEO and managing director of Radiopharm Theranostics, in a news release.¹ “Integrating RAD 101 [Pivalate; PET] with standard MRI has the potential to transform patient management and enable better treatment decisions for the more than 300,000 patients in the US diagnosed with brain metastases each year.”

RAD 101 is a novel small-molecule imaging agent designed for the diagnosis of suspected recurrent brain metastases originating from various solid tumors. The agent is radiolabeled with fluorine-18 (¹⁸F-RAD101).

It targets fatty acid synthase (FASN), a multi-enzyme protein that is overexpressed in many solid tumors, including cerebral metastases. Targeting FASN activity is intended to allow for more accurate detection of cancer cells.

Positive data from the phase 2a (NCT04807582)³ imaging trial at the Imperial College London showed significant tumor uptake with ¹⁸F-RAD101, independent of the primary tumor's origin. That study also indicated a potential for PET-MRI to serve as a noninvasive predictor of overall survival.

The ongoing phase 2b trial is a multicenter, open label, single-arm study evaluating the diagnostic performance of ¹⁸F-RAD101.²

The primary objective of the study is to measure concordance between ¹⁸F-RAD101 positive lesions and those identified via conventional imaging (MRI with gadolinium) in 30 patients with suspected recurrent brain metastases.

The secondary objective is to determine the accuracy, sensitivity, and specificity of RAD 101 in identifying tumor recurrence vs radiation necrosis in brain metastases previously treated with stereotactic radiosurgery (SRS).

Patient eligibility criteria includes but is not limited to patients having previously undergone SRS for brain metastases with preplanning images available for central review; having suspected recurrence in 1 to 5 previously treated lesions, identified via gadolinium-enhanced volumetric MRI; an ECOG performance status of 0 to 2; a life expectancy of ≥ 4 months; and a creatinine clearance of ≥ 60 mL/min (according to the Cockroft-Gault formula).

The study includes a 4-week screening phase, a 3-day imaging and safety window, and a 6-month data collection period. On day 1, patients will receive a single 370 MBq (10 mCi) with an allowable range of 10% above or below the target, administered over up to 30 seconds, followed by a saline flush. A whole-brain PET scan will occur approximately 60 minutes after dosing, with a window of 10 minutes before or after. High-resolution MRI will be conducted either simultaneously or later that day.

In June 2025, RAD 101 received fast track designation from the US FDA for distinguishing between recurrent disease and treatment effects in brain metastases, including cases involving leptomeningeal disease.¹

Radiopharm Theranostics plans to initiate a pivotal study by the end of 2026.

REFERENCES

1.Radiopharm Theranostics achieves primary endpoint in 92% of patients at interim analysis of RAD 101 phase 2b imaging trial in brain metastases. BioSpace. News release. December 15, 2025. Accessed December 18, 2025. https://tinyurl.com/2r44y73x

2.Phase 2b imaging study of RAD101 in participants with suspected recurrent brain metastases (RAD101). ClinicalTrials.gov. Updated November 24, 2025. Accessed December 18, 2025. https://clinicaltrials.gov/study/NCT06777433

3.Islam S, Inglese M, Aravind P et al. A hybrid [18F]fluoropivalate PET-multiparametric MRI to detect and characterise brain tumour metastases based on a permissive environment for monocarboxylate transport. Eur JNucl Med Mol Imaging  52, 2290–2306 (2025). doi: 10.1007/s00259-025-07118-0