Molecular Imaging in Alzheimer Disease: The Future is Promising

Editor’s Note: Moderated by Lawrence Tanenbaum, MD, FACR, Applied Radiology hosted a series of conversations with experts on Alzheimer disease imaging and management at the 2024 Radiological Society of North America Annual Meeting and Scientific Exhibition.

In this discussion, Dr Tanenbaum, Ana Franceschi, MD, associate professor of radiology at Lenox Hill Hospital, Hofstra/Northwell in New York City; and Adam Samchuck, senior product manager for PET Solutions at Siemens Healthineers, North America, explore the evolving role of molecular imaging in Alzheimer disease (AD) diagnosis, as well as the impact of emerging AD therapeutics.

Not that long ago, Alzheimer disease (AD) could be definitively diagnosed only at autopsy, when the deceased patient’s brain could be examined for the amyloid plaques and neurofibrillary tangles that characterize this insidious, fatal disease.

But the advent of positron emission tomography (PET) and molecular neuroimaging has paved the way to earlier diagnosis, as well as to new treatments that enable patients to maintain a higher quality of life for increasingly longer periods of time.

“About a third of patients diagnosed with Alzheimer's disease actually lack AD type pathology at autopsy. Similarly, in the community setting, about a third of patients with early signs and symptoms of Alzheimer's disease go undiagnosed,” says Ana Franceschi, MD, associate professor of radiology at Lenox Hill Hospital in New York City. But now, Dr Franceschi says, “Molecular imaging [allows us to] essentially differentiate patients with Alzheimer's disease from other types of neurodegenerative disorders” and to identify and select the proper candidates for treatment.

The Shift from FDG-PET to Amyloid and Tau Imaging

Prior to the emergence of amyloid and tau imaging, FDG-PET was the primary tool for evaluating neurological diseases. While FDG-PET (metabolic imaging) remains valuable for differential diagnoses, amyloid and tau PET imaging offer a significant advantage: definitive AD diagnosis while the patient is still alive.

“FDG helps differentiate underlying pathologies, while amyloid imaging confirms Alzheimer disease (pathology),” Dr Franceschi says, pointing out the importance of integrating both approaches to patient management.

The introduction of disease-modifying therapies (DMTs) such as anti-amyloid monoclonal antibodies dramatically increased demand for amyloid PET imaging, says Dr Tanenbaum, citing a “5000% increase over six months” in certain imaging regions.

Technological Advances and Efficiency in Imaging

Siemens Healthineers is addressing this rising demand. According to Adam Samchuck, senior product manager for PET Solutions at Siemens Healthineers, the company’s Biograph PET/CT systems offer high-resolution imaging with time-of-flight capabilities to increase diagnostic speed and accuracy.

“We focused on improving PET performance so clinics could increase their clinical offerings and flexibility,” Mr Samchuck explains. He adds that high-resolution imaging and quantification improve diagnostic confidence, particularly with respect to determining amyloid and tau burden.

Siemens Healthineers also recently announced plans to introduce a new, integrated MR-PET system, which could have the potential to provide further insights for Alzheimer’s imaging by combining highly sensitive molecular information with high-resolution anatomical MRI data. The panelists emphasized potential for hybrid imaging in this field.

The Role of Quantification

Amyloid and tau quantification are transforming clinical practice. Historically, amyloid PET has been viewed as a binary tool—positive or negative. However, as Dr. Franceschi explains, “ten to 15 percent of scans fell into a gray zone.” Quantification provides clarity to aid treatment decisions. FDA-approved platforms now allow quantitative amyloid values in clinical settings, aligning with clinical trials for monoclonal antibodies. Tau quantification is also promising. Lower tau burden correlates with better response to anti-amyloid therapies, making tau imaging crucial for treatment planning.

Reimbursement, Practical Impacts on Molecular Imaging Adoption

Although tau PET has primarily been used for research, recent changes in Medicare reimbursement are leading to its increased use in the clinical setting. These include the unbundling payments for PET scans and molecular imaging agents.

Until recently, many institutions, especially those that don't have more than one PET center, were faced with a decision of whether to allow this or not operate at all,” Dr. Franceschi notes. “Now, in terms of the role of tau PET, I think it is on the precipice of becoming truly clinically relevant.”

“We went from scanning maybe five to 10 patients before October 2023 to scanning 80 to a hundred patients a month immediately after CMS put out that statement highlighting their coverage of more than one scan per patient per lifetime,” she adds.

Neuroradiologists’ Role in Molecular Imaging

The growing demand for tau imaging highlights the need for neuroradiologists to engage more actively in molecular neuroimaging, with greater spatial resolution of PET/MRI systems compared to other modalities is critical for imaging brain structure, says Dr Tanenbaum. Dr Franceschi agrees and argues for integrating molecular and structural imaging data to further improve AD diagnosis and treatment.

“The findings of structural imaging such as the degree of vascular burden, atrophy pattern, the presence or absence of microhemorrhages really do impact how I interpret my PET imaging. And I think providing both sets of information to the clinicians at the same time again really does impact patient care in a meaningful way.”

Mr Samchuck finds this prospect exciting; he cites reduced radiation exposure (by avoiding CT for attenuation correction) and a more patient-centered and efficient workflow as benefits of the combined imaging approach.

A Promising Future

Ultimately, molecular neuroimaging is expected to play a transformative role in diagnosing and monitoring the treatment of Alzheimer disease. As technologies advance and new therapies emerge, collaboration between clinicians, manufacturers, and policymakers will be essential to the advancement of AD treatment.

“Just two years ago, we were at a place where there was not a single new therapeutic for Alzheimer's disease in 20 years,” says Dr Franceschi. “Now we have two drugs that have … FDA approval. I'm just excited to see what we'll be discussing at the next round table at RSNA 2025.”