FDA Accepts NDA for 18F-FET PET Imaging Agent in Glioma Management

The US FDA has accepted a new drug application (NDA) for ¹⁸F-fluroethyl-L-tyrosine (Pixclara; TLX101-Px), a PET imaging agent indicated for the characterization of progressive or recurrent glioma. The agent, also known as ¹⁸F-FET, is being developed to address a critical gap in neuro-oncology: the differentiation of true tumor progression from treatment-induced changes, such as pseudo-progression or radiation necrosis.¹

“Distinguishing tumor progression from treatment-related change remains one of the most challenging aspects of glioma care. PET imaging with ¹⁸F-FET is an important tool in clinical practice worldwide, and the FDA’s acceptance of this application is a meaningful step toward broader access for patients and clinicians in the United States,” said Patrick Wen, MD, E. Antonio Chiocca, MD, PhD, Family Endowed Chair in Neuro-Oncology at Mass General Brigham Cancer Institute, in a news release.

Addressing the Diagnostic Challenges in Neuro-Oncology

The management of adult and pediatric gliomas remains a complex challenge for oncologists and neuroradiologists. While MRI is the current standard of care for monitoring brain tumors, its specificity is often limited in the posttreatment setting. Standard MRI sequences frequently fail to distinguish between recurrent neoplastic tissue and radiation-induced effects, which can appear identical on contrast-enhanced scans.

According to the developer, Telix Pharmaceuticals, ¹⁸F-FET targets the large amino acid transporter (LAT1 and LAT2) systems. These transporters are significantly upregulated in gliomas compared with healthy brain parenchyma. Unlike ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG), which is limited by high baseline glucose metabolism in the brain, ¹⁸F-FET provides a high tumor-to-background ratio, allowing for more precise visualization of metabolic tumor volume.

Clinical Utility and Mechanism of Action

¹⁸F-FET is a synthetic amino acid analog. Its uptake into tumor cells is mediated by the LAT system, which reflects the increased protein synthesis and metabolic demands of malignant glial cells. By providing a metabolic map of the lesion, ¹⁸F-FET PET can assist clinicians in identifying the optimal biopsy site, planning radiation therapy volumes, and monitoring response to systemic treatments.

The clinical utility of ¹⁸F-FET is supported by its inclusion in several international guidelines, including those from the European Association of Neuro-Oncology (EANO) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). In the US, however, there is currently no FDA-approved amino acid PET agent specifically indicated for glioma imaging, making the review of ¹⁸F-FET a potentially significant shift in the domestic regulatory landscape.

Integration with Therapeutic Pipelines

The NDA submission for ¹⁸F-FET is part of a broader theranostic strategy in neuro-oncology. The imaging agent is being utilized as a companion diagnostic for the investigation of TLX101, a targeted 131I-labeled synthetic amino acid therapy. In the ongoing phase 1/2 IPAX-2 trial (NCT05450744), 18F-FET is used to evaluate treatment response and patient selection for the therapeutic candidate in the frontline setting for glioblastoma.²

Additionally, ¹⁸F-FET was employed in the completed IPAX-1 study (NCT04410887), which evaluated the safety and synergy of TLX101 with external beam radiation therapy in patients with recurrent glioblastoma. The data from these trials underscore the role of molecular imaging in quantifying tumor burden and refining the therapeutic window for radiopharmaceutical treatments.³

Regulatory Path and Future Outlook

The FDA has previously granted ¹⁸F-FET fast track designation, a process intended to facilitate the development and expedite the review of drugs that treat serious conditions and fill an unmet medical need.¹

Telix previously submitted an NDA for ¹⁸F-FET, which received a complete response letter in May 2025, requiring more clinical evidence to support the application.⁴

Kevin Richardson, CEO, Telix Precision Medicine, added in the news release, “The FDA’s acceptance of our NDA resubmission is an important milestone for Telix. We appreciate the FDA’s constructive engagement and look forward to working closely with the agency to urgently obtain approval and then bring this product to market for the benefit of patients.”

REFERENCES

1. FDA Accepts NDA for TLX101-Px (Pixclara®). News release. Telix. April 10, 2026. Accessed April 13, 2026. https://tinyurl.com/4xrje3zf

2. 131I-TLX-101 for Treatment of Newly Diagnosed Glioblastoma (IPAX-2) (IPAX-2). ClinicalTrials.gov. Updated January 21, 2026. Accessed April 13, 2026. https://clinicaltrials.gov/study/NCT05450744

3. Pichler J, Traub-Weidinger T, Spiegl K, et al. Results from a phase I study of 4-l-[131I]iodo-phenylalanine ([131I]IPA) with external radiation therapy in patients with recurrent glioblastoma (IPAX-1). Neurooncol Adv. 2024 Jul 29;6(1):vdae130. doi: 10.1093/noajnl/vdae130. PMID: 39211520; PMCID: PMC11358817.

4. Telix provides regulatory update on TLX101-CDx. News release. Telix Pharmaceuticals. May 1, 2025. Accessed April 13, 2026. https://tinyurl.com/4dmb647b