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

“Molecular imaging enables us to visualise functions and target structures using targeted tracers. This is vital for delivering precision medicine and tailoring treatment to the individual patient,” says Matthias Brendel, Deputy Director of the Department of Nuclear Medicine at LMU Munich. “Enormous progress is being made, particularly in the characterisation and therapeutic monitoring of neurodegenerative diseases, above all in Alzheimer’s disease.”

Confirming the diagnosis before treatment

According to the World Health Organization, 57 million people were living with dementia worldwide in 2021. Alzheimer’s disease is the most common form of dementia, accounting for 60% to 70% of all cases.
“With an amyloid PET scan we can visualise the amyloid in the brain of a person with dementia and determine whether it is actually Alzheimer’s disease or another form of dementia,” explains Brendel. “This is important because the new therapy using monoclonal antibodies against beta-amyloid – lecanemab and donanemab, which have been approved in recent years by the FDA and the European Commission – can only be effective in cases of Alzheimer’s disease.”
Blood and cerebrospinal fluid biomarkers can also support the diagnosis but in many cases leave some uncertainty, according to Brendel, who recommends an amyloid PET scan for confirmation before starting treatment.

Showing how treatment is working

Amyloid PET can also help clinicians monitor the response to treatment. “The scan shows at what point the amyloid level in the brain falls below the detection limit, meaning the scan is amyloid-negative. Many patients experience this after taking donanemab for 12 months, even though the treatment is generally designed to last 1.5 years. In a phase 3 trial for donanemab published in the Journal of the American Medical Association (JAMA), 52% of participants who received the drug completed their entire course of treatment in less than 12 months. Once the amyloid has been cleared, clinicians may be able to consider ending treatment,” says the nuclear medicine specialist.

Treating Alzheimer’s before symptoms progress

Amyloid-beta is a protein that occurs naturally in the brain. In people with Alzheimer’s disease, it accumulates between the brain cells, initially forming small clumps and later developing into large plaques. This process begins years before the first symptoms.
“The tracers used in PET scans bind to the compact plaques and visualise them, while the drugs act on the early aggregates and can therefore slow the progression of the disease by up to 30% at an early stage, according to clinical trials,” points out Brendel.
The earlier treatment can be started, the better, according to the nuclear medicine specialist. Lecanemab and donanemab are therefore aimed at patients in the early stages of the disease, at mild cognitive impairment or mild dementia.

Tau PET: predicting the course of the disease

In Alzheimer’s disease, amyloid-beta works together with another protein, tau, to disrupt communication between nerve cells, which then die off progressively. Although no approved drug yet targets tau deposits, tau PET scans are already of great value, says Brendel.
“At our clinic alone, more than 500 amyloid and tau PET scans are carried out each year to diagnose Alzheimer’s disease. Using the tracer employed at the LMU Medical Centre, we also obtain a binding curve which allows us to determine whether there are amyloid-beta-associated tau deposits and to assess the extent of neuronal damage. This enables us to make accurate predictions regarding the progression of the disease and the likelihood of a positive response to treatment.”
The same phase 3 trial with donanemab published in JAMA showed that patients with low levels of tau respond better to the new drugs than those with high levels of tau in the brain. “Amyloid PET is important for establishing a definitive diagnosis of Alzheimer’s in general,” says Brendel. “Tau PET has the greatest potential because it can help us determine, with a high degree of certainty, who is particularly suitable for the therapies that are already available and who would benefit little from them.”

Looking ahead: a new antibody in development

A phase 3 trial for trontinemab, an amyloid antibody that crosses the blood-brain barrier using its own shuttle mechanism, is currently underway. “This could significantly increase the availability of the antibody in the brain and reduce side effects. Treatment could then be completed more quickly, possibly within three to four months. Here too, amyloid PET would be needed to confirm that treatment has been successful, but we must, of course, await the completion of the regulatory approval trials,” adds Brendel.

About IAKW-AG and EANM

IAKW-AG (Internationales Amtssitz- und Konferenzzentrum Wien, Aktiengesellschaft) is responsible for the maintenance of the Vienna International Centre (VIC) and the operation of the Austria Center Vienna. With 21 halls, 134 meeting rooms and around 26,000 m² of exhibition space, the Austria Center Vienna is Austria’s largest conference centre and ranks among the leading players in the international conference industry. The European Association of Nuclear Medicine (EANM) is based in Vienna and is Europe’s largest non-profit medical organisation dedicated to nuclear medicine. Since its foundation in 1985, the EANM has been bringing together healthcare professionals, other medical societies, EU policy-makers and industry representatives to ensure that patients across Europe have easy access to nuclear medicine.

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