FDA Grants Fast Track Designation to RAD101 Imaging for Brain Metastases

RAD101, an imaging small molecule that targets fatty acid synthase, a multi-enzyme protein that catalyzes fatty acid synthesis, which is overexpressed in various solid tumors, including cerebral metastases.

The FDA has granted fast track designation to RAD101, an imaging small molecule that targets fatty acid synthase (FASN), to distinguish between recurrent disease and the treatment effect of brain metastases that originate from different solid tumors including leptomeningeal disease, according to a press release from the developer, Radiopharm Theranostics.¹

FASN is a multi-enzyme protein that catalyzes fatty acid synthesis, which is overexpressed in various solid tumors, including cerebral metastases.

RAD101 is currently under investigation in a multicenter, open-label, single-arm phase 2b trial (NCT06777433) that is evaluating the image performance of ¹⁸F-RAD101 PET in those with suspected recurrent brain metastases from solid tumors.

“The FDA’s fast track designation for RAD101 highlights the seriousness of recurrent brain metastases as a condition and the unmet medical need for innovative products that can differentiate between tumor recurrence and radiation necrosis or pseudoprogression,” Riccardo Canevari, chief executive officer and managing director of Radiopharm Theranostics, stated in the press release.¹ “RAD101 represents a promising advancement in improving diagnostic precision for brain metastases, offering hope for more effective clinical decision-making in the over 300,000 patients diagnosed annually in the US. We are excited to advance our phase 2 clinical trial and anticipate sharing topline results in the second half of 2025.”

The trial enrolled a total of 30 patients with confirmed recurrent brain metastases from solid tumors of different origins. Study treatment consisted of a single dose of ¹⁸F-RAD101 at a maximum of 370 MBq (10 mCi) as a slow intravenous bolus injection over a maximum of 30 seconds on day 1, followed by a saline flush.²

Patients were 18 years or older with a histopathologically confirmed advanced solid tumor diagnosis—lung, breast, colon, kidney, or melanoma—and a known history of brain metastases who previously underwent stereotactic radiosurgery (SRS) for their brain metastases prior to study screening. It was also required that patients had suspected, not confirmed, recurrent brain metastases in at least 1 but no more than 5 lesions previously treated with SRS within 6 weeks of study day 1. An ECOG performance status from 0 to 2, a life expectancy of at least 4 months, and creatinine clearance of at least 60 mL per minute via the Cockroft-Gault formula were also required.

Exclusion criteria included a history of known additional malignancy progressing or requiring treatment, brain surgery within 4 weeks before the screening MRI; whole-brain radiation therapy or SRS within 6 weeks of day 1, any medical condition that would prevent the patient’s full study participation in the investigator’s judgement, and history of uncontrolled allergic reactions and/or known hypersensitivity to RAD101 or any of its excipients.

The primary end point of the study was concordance between ¹⁸F-RAD101–positive lesions and those seen in conventional imaging using MRI with gadolinium in patients with suspected brain metastases. Secondary end points included the accuracy, sensitivity, and specificity of RAD101 in identifying tumor recurrence vs radiation necrosis in previously SRS-treated brain metastases.

It was noted that positive data from the Imperial College of London’s phase 2a imaging trial (NCT04807582) demonstrated that RAD101 showed significant tumor uptake, independent from the tumor of origin, and that PET-MRI may represent a non-invasive prediction of overall survival.³

The results from this trial, which were published in the European Journal of Nuclear Medicine and Molecular Imaging, highlighted that of 12 patients who were treatment-naïve and 10 patients who were previously treated with brain radiation, all brain metastases, regardless of tumor of origin, were detected by ¹⁸F-RAD101 imaging.

References

1. Radiopharm Theranostics granted U.S. Food and Drug Administration fast track designation for RAD101 imaging in brain metastases. News release. June 11, 2025. Accessed June 12, 2025. https://tinyurl.com/3ankvc2u
2. Phase 2b imaging study of RAD101 in participants with suspected recurrent brain metastases (RAD101). ClinicalTrials.gov. Updated March 17, 2025. Accessed June 12, 2025. https://tinyurl.com/24fsb6z5
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 J Nucl Med Mol Imaging. 2025;52(7):2290-2306. doi:10.1007/s00259-025-07118-0