Cardiac Amyloidosis: Alzheimer’s Disease Of The Heart

Over time the protein buildup can damage the heart, and the heart struggles to pump, leading to congestive heart failure and death. Symptoms of cardiac amyloidosis include but are not limited to leg swelling, shortness of breath, heart weakness, dizziness, fatigue, disrupted sleep, swollen liver, kidney problems, and irregular heartbeat, as well as thickening and stiffening of the heart muscle.  Around 20% of people with amyloid proteins built up in their hearts will experience early death.

“Therapies that slow the progression of amyloid deposition have been developed; however, they are not effective in patients with late-stage disease. Therefore, the ability to detect cardiac amyloidosis early is critical,” noted Jonathan Wall, PhD, director of the Amyloidosis and Cancer Theranostics Program and professor at the University of Tennessee Graduate School of Medicine in Knoxville, Tennessee. “Unfortunately, there are currently no Food and Drug Administration (FDA)-approved imaging agents that detect cardiac amyloidosis.”

To help address this issue, researchers have developed a novel radiotracer that can produce high-quality and readily interpretable images of cardiac amyloidosis. As the first amyloid-specific and pan-amyloid binding radiotracer designed for planar and SPECT/CT imaging, 99mTc-p5+14 could play an important role in the early detection and treatment of cardiac amyloidosis. The findings from this research were presented at the 2024 Society of Nuclear Medicine and Molecular Imaging Annual Meeting.

In the first-in-human study, the technetium-99m labeled variant of the pan-amyloid reactive peptide p5+14 (99mTc-p5+14) was tested in five healthy volunteers and 30 patients newly diagnosed with light chain or transthyretin amyloidosis underwent 99mTc-p5+14 imaging with standard planar gamma scintigraphy and SPECT/CT. 

Blood was collected to assess serum biomarkers, and a transthoracic echocardiogram was performed. Standard 99mTc-pyrophosphate imaging was also performed on most patients at 72 hours after 99mTc-p5+14 image acquisition. The planar and SPECT/CT images generated using 99mTc-p5+14 were of high quality and readily interpretable at both one and three hours post-injection. Patients with amyloid cardiomyopathy had significant 99mTc-p5+14 uptake in the heart, whereas no cardiac uptake was observed in healthy subjects.

“Early and accurate diagnosis of cardiac amyloidosis is crucial to ensure the most positive outcomes for patients,” said Wall. “Imaging with 99mTc-p5+14 could provide an easy-to-use and interpret technology that could be employed in the community cardiology setting, where SPECT imaging is common, as a rapid screen for amyloid cardiomyopathy in the future.”

Currently, the radiotracer is involved in ongoing early-stage clinical evaluation at the University of Tennessee Graduate School of Medicine in conjunction with Attralus Inc., to assess safety and efficacy in patients with cardiac amyloidosis and healthy subjects. Data and insights from the research are expected to support the initiation of a Phase 3 study and the approval submission to the FDA in the future. 

Abstract 241277. “Preliminary Evaluation of 99mTc-Labeled Peptide p5+14 for the Detection of Cardiopulmonary Amyloidosis Using SPECT/CT and Planar Gamma Scintigraphic Imaging,” Jonathan Wall, Emily Martin, Alan Stuckey, Bryan Whittle, Joseph Jackson, Angela Williams, Trevor Hancock, R. Eric Heidel, Muddassir Mehmood, Anne Kassira, Ronald Lands, Hannah Watson, Rebecca Hung, Stephen Kennel, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee.