PET/CT biomarkers enable clinicians to advance Alzheimer’s disease care

With the latest molecular imaging tools and biomarkers to enhance diagnostic accuracy and enable disease-modifying treatments, clinicians are paving the way for hope.

The burden of Alzheimer’s disease (AD) continues to threaten the world’s growing aging population, but progress in research, diagnostics, and new treatments offers patients hope to slow the progression of disease today and the promise of hope for the future. Medical imaging, and specifically PET/CT imaging with radiotracers targeting specific disease biomarkers, allows clinicians the opportunity to more accurately diagnose neurodegenerative disorders such as AD, quantify their pathology in the brain, and pursue disease-modifying therapies, much like oncologists’ approach to cancer diagnostics, staging, and treatment.

It is estimated that 40 million people are suffering from dementia throughout the world, and this number is predicted to double every 20 years until approximately 2050.¹ Though dementia is commonly associated with AD and may constitute 60-80 percent of AD cases², there are many other neurodegenerative disorders and clinical conditions that can also cause dementia, such as frontotemporal dementia, vascular brain disease, Parkinson’s disease, or structural abnormalities, such as a brain tumor.

The lack of non-invasive diagnostic imaging biomarkers has previously precluded accurate diagnosis and appropriate management of AD. The introduction of PET/CT imaging with a beta amyloid biomarker, also called amyloid PET imaging, to detect amyloid in living patients enables clinicians to evaluate patients for AD accurately.

In addition to structural and functional imaging information obtained with CT and MRI, evaluation with PET/CT and PET/MR can illustrate accumulation of amyloid plaques in the brain, hallmark characteristics of AD, helping clinicians to rule out other causes of dementia and confidently diagnose and manage patients with confirmed AD. The cognitive symptoms of AD are associated with the damage caused by the accumulation of these plaques. Although amyloid PET can illustrate the accumulation of plaques in the brain, other imaging modalities are still often utilized if clinicians have a differential diagnosis to consider.

From the perspectives of the treating physician and the radiologist who is part of the patient’s multidisciplinary care team, two leading physicians agree on imaging’s key role in enabling diagnostic accuracy in cases of neurodegenerative disorders and AD.

“One of the main reasons why a patient would be referred for brain PET/CT or PET/MRI would be dementia, or cognitive impairment with AD being a leading differential diagnostic consideration in many patients,” notes Dr. Jana Ivanidze, neuroradiologist and nuclear medicine physician practicing at a leading academic institution’s hospital in New York City, New York, USA. “Often, MRI is the preferred initial imaging exam for patients presenting with cognitive impairment to give us an understanding of brain volume loss pattern, whether it is global or regional because that might give us a clue as to the diagnosis. We also want to make sure we are excluding any structural problems, such as hydrocephalus or a brain tumor that could be causing memory impairment.”

Dr. Monica Crane provides comprehensive patient care for AD and related neurodegenerative dementias at the Tennessee Memory Disorders Foundation in Knoxville, Tennessee, USA. According to Dr. Crane, the number of patients who need care is staggering, and her team relies on medical imaging as a key diagnostic resource.

“In terms of progress and diagnostic accuracy [in AD], I feel like we’re retelling the cancer story. We can look historically at other diseases and care paths, like breast cancer, for example. When breast cancer was diagnosed in the past, a radical mastectomy was routine. We no longer do that. There are different types of treatments for different stages and cell types. The same is happening right now in AD. Imaging with targeted biomarkers allows us a sensitive and specific diagnosis of AD as well as the ability to quantify amounts of pathology and see where that pathology is located in the brain. AD itself is extraordinarily heterogeneous. But now we can pinpoint and better understand AD by capturing both the topographic and the magnitude of disease.” 

“PET/CT is vital in the diagnosis of AD and other neurodegenerative diseases,” Dr. Ivanidze concurs. “Additionally, the availability of more precise quantitative tools in recent years allows for the visualization of characteristic patterns and abnormalities in the cerebral cortex, which allows us to distinguish between AD, frontotemporal dementia, and DLB.”

2023 marked some significant milestones in the AD care path. Lecanemab became the first FDA-approved treatment to slow the decline of AD in adults following aducanumab, which was discontinued.³ This disease-modifying therapy is an antibody that removes the amyloid protein from the brain and reduces the amyloid plaque build-up that is thought to cause AD to worsen.

“Changing the narrative is so important right now in AD,” explains Dr. Crane. “The availability of the first monoclonal antibody really opened the door. It was a huge and momentous achievement and allowed lecanemab to emerge. Lecanemab is offering tremendous hope in the field.”

“And in the past year, we saw the expansion of amyloid PET insurance coverage,” adds Dr. Ivanidze, “which represents a major milestone, and we are now seeing amyloid PET enter clinical practice in the work-up of patients with cognitive impairment and suspected AD.”

To be considered for lecanemab therapy, a confirmed diagnosis of AD needs to be obtained through one of two avenues: amyloid PET imaging or biomarkers found in cerebral spinal fluid (CSF). While the CSF measurement method has been clinically available for a longer time and may be more widely accessible, there can be drawbacks.

“With CSF measurements, there are inconsistencies between reference ranges, just like any lab test is going to be a bit different depending on where it’s getting sent,” Dr. Ivanidze explained. “Other conditions may also be present in a patient with AD that can affect the concentration of AD biomarkers in the CSF. Also, there may be inconsistencies with the collection process. It is overall a more invasive experience for the patient, requiring a lumbar puncture. The advantage of amyloid PET imaging is that it is a noninvasive procedure that allows quantitative assessment of the geographic distribution of cortical beta amyloid plaque deposition.”

Having that information can help clinicians see how the quantity of plaque changes over the course of Lecanemab therapy. “What exactly do we do with that information?” Dr. Ivanidze explains. “We have to learn more about it. For example, serial amyloid PET can help us assess the change in cortical beta-amyloid plaque burden after a patient undergoes lecanemab therapy. While amyloid PET follow-up is not written into the clinical management protocols in patients undergoing lecanemab therapy at the moment, evaluating change in beta-amyloid burden over time and how it is associated with change in cognitive symptoms is a key focus area of research. Does the patient’s cognition improve as their beta amyloid burden decreases? These are things we need to continue to study, but that’s another big advantage of amyloid PET. It gives us this regional information and we can evaluate changes over time. At the moment, amyloid PET follow-up is not written into the clinical management protocols, but that’s something that all of us are very interested in seeing.”

Dr. Crane has been an active participant in many clinical trials involving AD radiotracers and treatments. Siemens Healthineers PETNET Solutions, Inc., has been a supplier of amyloid PET radiotracer imaging agents since trial stages and continues to provide widespread access for amyloid PET scanning.

“I believe in participating in the trials,” Dr. Crane explains, “even with the understanding that some of them will be more or less successful. But I feel like the individual patients that had access to radiotracers before it was available to the public, that was an incredible gift.”

To support continued growth in PET/CT imaging so that more patients can have access to care, PETNET Solutions operates an expansive network of cyclotron-equipped radiopharmacies that are needed to manufacture and distribute radiotracers and targeted biomarkers. PETNET Solutions also supports the growing portfolio of research radiopharmaceuticals that are continually being developed to target additional diseases.

Crane continues, “PETNET Solutions has allowed us to access the latest radiotracers. It’s fabulous that PETNET Solutions is reaching out to partner with smaller organizations to allow broader access to these tracers outside of the large research centers. The aging population is growing, and we serve a very wide community of patients.”

Despite the progress made in diagnosing and treating AD, the growing aging population presents a looming challenge. The Tennessee Memory Disorders Foundation not only provides comprehensive care for AD patients and patients with related dementias but also encourages students and professionals to pursue careers in the dementia field.

“One big need is that there are very few clinical providers in this space,” says Dr. Crane. “So, part of my goal is to really inspire others to pursue this field. We have a very large undergraduate and postgraduate internship program. We have been very successful in our efforts, and I have seen a number of my mentees pursue the fields of geriatrics, neurology, aging, and other specialties. I think students come away with an experience, understanding, and a respect for the disease.”

Dr. Crane is also focusing on changing the narrative in AD care to be more optimistic and to provide education where patients get their primary healthcare assessments. “AD is everyone’s problem. We are focused on teaching and outreach in the primary care world. We are all in this together. It’s about education and community. I’ve always been an optimist, and I have always believed that AD will be cured. This future thinking can push the field as opposed to getting stuck with how things are done now. It’s possible that capturing the data on the quantity and location of disease in the brain may help us understand and stage the disease even more accurately. As progress continues to be made, we will be able to understand even more about the differences and nuances of AD. That’s where we are making the most headway.”

Claudette Lew is a freelance medical writer and editor.