FDA Grants Fast Track Designation to RAD101 for Imaging of Brain Metastases

FDA

The FDA has granted fast track designation to RAD101, an investigational imaging agent, to differentiate between recurrent brain metastases and treatment-related effects in patients with cerebral metastases originating from various solid tumors, including those with leptomeningeal involvement.1

This designation is intended to facilitate the expedited development and review of therapies that address serious conditions and demonstrate the potential to fill unmet medical needs.

“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 pseudprogression,” Riccardo Canevari, chief executive officer and managing director of Radiopharm Theranostics, stated in a news release.

RAD101 is a novel small molecule that targets fatty acid synthase (FASN), a multi-enzyme protein involved in fatty acid synthesis that is frequently overexpressed in a range of solid tumors, including those with central nervous system involvement. By targeting FASN activity, RAD101 may enable more precise imaging of malignant lesions within the brain, potentially improving the diagnostic accuracy in differentiating tumor recurrence from post-treatment changes.

The agent is being investigated in an open-label, single-arm, phase 2b trial (NCT06777433).2 Investigators are enrolling patients at least 18 years of age with histopathologically confirmed advanced solid tumors with a known history of brain metastases. Eligible tumor types include lung, breast, colon, kidney, or melanoma. Prior treatment with stereotactic radiosurgery (SRS_ for brain metastases and pre-planning images are required. Patients need to have suspected but not confirmed recurrent brain metastases in at least 1 but not more than 5 lesions previously treated with SRS, based on gadolinium-enhanced volumetric MRI.

Other key inclusion criteria comprise an ECOG performance status of 0 to 2; a life expectancy of at least 4 months; and adequate creatinine clearance. Key exclusion criteria include a history of a known additional malignancy that is progressing or requires treatment; brain surgery within 4 weeks before screening MRI; and whole brain radiation or SRS within 6 weeks of the first day of the study.

On day 1, patients are receiving a single dose of RAD101 at a maximum 370 MBq (10 mCi).

The primary objective of the study is to evaluate the concordance between lesions identified by 18F-RAD101 positron emission tomography (PET) imaging and those detected through conventional magnetic resonance imaging (MRI) with gadolinium contrast.

Key secondary end points include the diagnostic accuracy, sensitivity, and specificity of 18F-RAD101 in distinguishing between true tumor recurrence and radiation necrosis in brain metastases previously treated with SRS. Investigators note that the ability to differentiate these entities is clinically important, as it informs appropriate management strategies and avoids unnecessary interventions.

The ongoing U.S. phase 2b clinical trial plans to enroll a total of 30 participants across multiple sites, all of whom have suspected recurrent disease following prior treatment.1

Phase 2a Trial

A previously published clinical study (NCT04807582) evaluated the novel radiotracer 18F-RAD101 in the detection of brain metastases using a hybrid imaging modality that integrates PET with MRI.3 The study included 22 patients, comprising 12 treatment-naive individuals and 10 patients who had received prior brain radiotherapy.

The analysis demonstrated that 18F-RAD101 successfully identified all brain metastases irrespective of the tumor of origin. The radiotracer exhibited high tumor-to-background uptake ratios, supporting its potential utility in detecting both previously treated and untreated lesions.

References

1. RAD granted US FDA fast track for RAD101 metastases imaging. News Release. Radiopharm Theranostics. June 11, 2025. Accessed June 11, 2025. https://investorhub.radiopharmtheranostics.com/announcements/6998425
2. Phase 2b imaging study of RAD101 in participants with suspected recurrent brain metastases (RAD101). ClinicalTrials.gov. Updated March 17, 2025. Accessed June 11, 2025. https://clinicaltrials.gov/study/NCT06777433
3. Islam S, Inglese M, P. Aravind, et al. A hybrid [18F]fluoropivalate PET-multiparametric MRI to detect and characterise brain tumour metastases based on a permissive environment for monocarboxylate transport. European Journal of Nuclear Medicine and Molecular Imaging. February 7, 2025. doi10.1007/s00259-025-07118-0