Dual-Purpose Imaging Agents for PET and MRI Scanners Could Diagnose Neurodegenerative Diseases Earlier

Alzheimer's disease, a neurodegenerative condition, impairs brain function and cognitive abilities. It is classified along with Parkinson's disease, amyotrophic lateral sclerosis, and other disorders as an amyloid disease. Amyloids, comprising small groups of abnormally fibrous or misfolded proteins, typically serve no functional purpose in the body. A hallmark of Alzheimer’s is the formation of amyloid plaques, which are accumulations of beta-amyloid peptide aggregates. These peptides, short chains of amino acids, are precursors to proteins. Neuroinflammation and oxidative stress in the brain are also significant indicators of Alzheimer's. The diagnosis and treatment of such neurodegenerative diseases are challenging due to the blood-brain barrier, a semipermeable system of blood vessels and capillaries that controls the flow of ions, molecules, and cells between the blood and the brain. For imaging and therapeutic agents, composed of molecules or antibodies, to be effective, they must be able to pass through this barrier.

Currently, diagnosing Alzheimer’s disease with high accuracy is possible only post-mortem by identifying amyloid aggregates. This necessitates the development of diagnostic tools capable of detecting soluble beta-amyloid peptide aggregates and larger amyloid plaques in living patients. PET and MRI are two non-invasive imaging techniques frequently used clinically. Yet, there are no MRI contrast agents targeting amyloid aggregates, and existing FDA-approved PET imaging agents either fail to detect small-scale amyloid abnormalities or sometimes result in false-positive test results for Alzheimer’s. Thus, it is vital to create diagnostic tools targeting smaller beta-amyloid peptides and other signs of neuroinflammation and oxidative stress.

Now, a research team from Beckman Institute (Urbana, IL, USA) comprising a synthetic chemist, medical imaging expert, and neurologist are developing enhanced diagnostic tools and imaging agents for early-stage Alzheimer’s detection and other neurodegenerative diseases. Supported by a USD 3 million grant from the U.S. National Institute on Aging of the National Institutes of Health, the team aims to create and test multi-modal imaging agents for Alzheimer’s and related dementias over five years. These agents, designed to penetrate the blood-brain barrier and be compatible with both PET and MRI scanners, will facilitate earlier detection of neurodegenerative diseases and significantly aid in advancing therapeutic approaches.

Developing multi-modal tools for use in both PET and MRI will provide deeper insights into Alzheimer's risk, diagnosis, and progression. The researchers have already synthesized specialized molecules that can cross the blood-brain barrier and detect both small soluble beta-amyloid peptides and larger insoluble amyloids. They have also developed a copper-based PET imaging agent, which successfully visualized amyloid plaques in transgenic Alzheimer’s mice. Going forward, the team anticipates that these agents can be adapted for human use, enabling earlier detection of multiple markers of Alzheimer’s and other neurodegenerative diseases.

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