A Bright Future for Nuclear Medicine in Neuro-Oncology Clinical Trials

By PSI radiopharmaceutical team: Rhonda Critchlow, Head of Therapeutic Strategy; Dylan Stoy, Director of RLT Therapeutic Strategy; Vince Calderon, Director of Therapeutic Strategy; Melissa Cohen, Site Technology Specialist

Our team recently attended the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2025 Annual Meeting, where the outlook for future therapies has never been so bright (pun fully intended).

From CZT scanners and their positive impact on dosimetry in clinical trials to novel uses for ⁴⁴Sc and ⁷¹As in radiopharmaceuticals, each session was full of exciting information. However, the most intriguing advances involved the future of nuclear medicine in neurological applications, with molecular imaging and radioligand therapy (RLT) in neuro-oncology at the forefront.

Diagnostics: Moving from MRI to Amino Acid PET

The therapeutic landscape for malignant brain tumors such as gliomas, which account for 22.9% of all brain and other CNS tumors and 80% of malignant brain tumors in the US, remains challenging.^[1],[2] Conventional treatment modalities such as surgery, chemotherapy and radiation can only extend survival for a short time due to the aggressive nature of these cancers and difficulty for other therapeutics to cross the blood-brain barrier (BBB).

The gold standard for diagnosis and imaging of brain tumors is MRI, as it provides highly detailed images, but limitations exist in differentiating between healthy and malignant tissue. These limitations can cause issues for the patient and physician, including delays in treatment and incorrect treatment decisions.

Imaging with PET amino acids is one potential way to overcome these challenges. Researchers are examining the use of tracers such as ¹¹C-Met, ¹⁸F-FET, and ¹⁸F-FDOPA because L-type amino acid transporters (LATs), which are overexpressed in gliomas and brain metastases, facilitate their uptake. High radiopharmaceutical uptake in brain tissue and diminished uptake in healthy tissue generate excellent tumor differentiation and easy-to-read scans.

When comparing MRI to ¹⁸F-FET imaging of glioblastoma, ¹⁸F-FET PET was superior in determining tumor extent, improving parameters and radiation planning.^[3] This is important as overall survival is significantly improved when over 98% of the tumor volume is resected.^[4] The most common indication for Amino Acid PET imaging is to distinguish between recurrence or radiation necrosis. In one clinical study of 189 patients, ¹⁸F-FET resulted in a change in treatment of 53% of patients with suspected recurrent disease.^[5]

Treatment: The Role of Radioligand Therapy 

While treatment for brain tumors is challenging and complex, radioligand therapy offers a promising alternative. By combining tumor-specific ligands with radioactive isotopes, RLT enables the precise targeting of malignant cells while sparing healthy brain tissue. Early-phase clinical trials have shown encouraging results, with radioligands successfully crossing the BBB, delivering targeted radiation to the tumor.

One type of brain tumor that is highly suitable for RLT is meningiomas. While most meningiomas are benign and slow-growing, depending on their size and location, these tumors can cause a variety of symptoms. Approximately 20% of meningiomas are malignant, and the current preferred treatment option is complete resection and/or external beam radiation therapy, posing a challenge as surgical resection is not possible in 30-40% of meningiomas.^[6]

This is where RLT comes in. About 90% of meningiomas overexpress somatostatin receptors (SSTRs) on both the surface and endothelium of peritumoral vessels, making this cancer an excellent candidate for ¹⁷⁷Lu-DOTATATE therapy.^[7],[8]

Overcoming the challenges associated with delivering treatments across the BBB is essential, especially since brain tumors can compromise the integrity of this barrier. Brain RLT administration methods can be either systemic or localized to enhance efficacy. Innovative strategies include the use of direct catheters for targeted delivery, convection-enhanced delivery through microcatheters, focused ultrasound techniques that utilize low frequencies to open the BBB temporarily, and MRI-guided transcranial devices for precise treatment application.

Future Potential and Considerations for Clinical Research

Our radiopharmaceutical team began thinking of how RLT could potentially be combined with current treatment practices, asking questions such as:

• Can we use RLT to treat the tumor completely?
• What if we use it as a combination therapy to shrink the tumor first, then resect it or do radiation treatment?
• How do we successfully deliver drugs across the BBB and what are the implications and limitations of the more invasive administration methods?

As advancements in molecular imaging and RLT continue to transform the neurological diagnosis and treatment options, one thing is certain: delivering optimal care to these patients requires a collaborative, interdisciplinary approach that brings together cross-functional teams, including Neuro-oncology, Neurosurgery, Nuclear Medicine, and Radiation Therapy.

This teamwork is essential to ensure that patients receive the highest quality of care throughout clinical trials. This includes:

• managing the need for precise dosimetry to ensure patient safety while maximizing therapeutic efficacy.
• addressing potential regulatory challenges when combining radioactive components with biological targeting molecules.
• working to harmonize treatment standards across different countries and sites.

Mastering the clinical strategy and trial oversight is essential to a successful trial.