Brain PET scans help select and monitor patients for new Alzheimer's drugs

Brain PET scans are increasingly crucial in the diagnosis and treatment of Alzheimer's disease, providing clinicians with insights into the biological changes associated with the condition. Amyloid PET imaging confirms the presence of amyloid pathology, supporting treatment decisions for patients on anti-amyloid drugs, while tau PET scans offer additional information about disease progression and prognosis.

The 39th Annual Congress of the European Association of Nuclear Medicine, held in Vienna from October 17 to 21, will discuss the practical applications of these PET scans in routine clinical use and explore recent advancements in nuclear medicine. Matthias Brendel, deputy director of the Department of Nuclear Medicine at LMU Munich, emphasizes the importance of molecular imaging in delivering precision medicine and tailoring treatment to individual patients.

Progress in characterizing and monitoring neurodegenerative diseases, particularly Alzheimer's, is rapid. An amyloid PET scan can visualize amyloid in a person's brain to determine if they have Alzheimer's disease or another form of dementia, which is essential for determining the effectiveness of new therapies like monoclonal antibodies against beta-amyloid.

These therapies, such as lecanemab and donanemab, can only be effective in cases of Alzheimer's disease. Amyloid PET scans also help monitor treatment response, showing when amyloid levels in the brain fall below the detection limit, indicating amyloid-negative status. Many patients experience this after 12 months of donanemab treatment, despite the treatment typically lasting 1.5 years.

In a phase 3 trial for donanemab, 52% of participants who received the drug completed their entire course within 12 months. Once amyloid is cleared, clinicians may consider ending treatment. Amyloid-beta, a naturally occurring protein in the brain, accumulates in Alzheimer's disease, forming aggregates that disrupt nerve cell communication and lead to cell death.

Tau PET scans, although not yet an approved drug target, are valuable in assessing neuronal damage and predicting disease progression. These scans are already used in over 500 cases annually at the LMU Medical Centre. Tau PET can help identify patients particularly suitable for existing therapies and those who would benefit less from them.

A phase 3 trial for trontinemab, an amyloid antibody with a unique shuttle mechanism, is underway, which could significantly increase antibody availability in the brain and reduce side effects, potentially shortening treatment duration to three to four months. Amyloid PET scans are vital for confirming amyloid pathology and guiding anti-amyloid treatment in early Alzheimer's disease, while tau PET informs prognosis and predicts treatment response, with lower tau levels associated with better outcomes.