Cardiac amyloidosis, also known as Alzheimer’s disease of the heart, can be inherited or acquired. Systemic amyloidosis is an incurable disease in which abnormal amounts of proteins build up in tissues and organs. Treatment advances Cardiac amyloidosis Although prognosis has improved significantly, median survival remains poor at approximately 3 to 5 years.
Over time, the protein builds up and damages the heart, causing it to be unable to pump properly, leading to congestive heart failure and death. Symptoms of cardiac amyloidosis include, but are not limited to, swollen legs, shortness of breath, cardiac weakness, dizziness, fatigue, sleep problems, liver enlargement, kidney damage, irregular heartbeat, and thickening or hardening of the heart muscle. Approximately 20% of people with amyloid protein buildup in the heart die prematurely.
“Although treatments have been developed to slow the progression of amyloid deposits, they are ineffective in patients with advanced disease, making the ability to detect cardiac amyloidosis early critical,” notes Jonathan Wall, PhD, professor and director of the Amyloidosis and Cancer Theranostics Program at the University of Tennessee College of Medicine in Knoxville, Tenn. “Unfortunately, there are currently no Food and Drug Administration (FDA)-approved imaging agents to detect cardiac amyloidosis.”
To address this issue, researchers have developed a new radiotracer that can produce high-quality, easily interpretable images of cardiac amyloidosis. 99mTc-p5+14, the first amyloid-specific and pan-amyloid-binding radiotracer designed for planar and SPECT/CT imaging, may play an important role in the early detection and treatment of cardiac amyloidosis. The findings were presented at the 2024 Society of Nuclear Medicine and Molecular Imaging Annual Meeting.
In a first-in-human study, a technetium-99m-labeled variant of the pan-amyloid-reactive peptide p5+14 (99mTc-p5+14) was tested in five healthy volunteers, and 30 patients with newly diagnosed light-chain or transthyretin amyloidosis underwent 99mTc-p5+14 imaging with standard planar gamma scintigraphy and SPECT/CT.
Blood was drawn to assess serum biomarkers, transthoracic echocardiography was performed, and standard 99mTc-pyrophosphate imaging was performed in most patients 72 hours after 99mTc-p5+14 image acquisition. Planar and SPECT/CT images generated with 99mTc-p5+14 were of high quality and easily interpretable at both 1 and 3 hours after 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 essential to ensure the best outcomes for patients,” said Wall. “Imaging with 99mTc-p5+14 may provide an easy-to-use, easy-to-interpret technology that can be used in the future as a rapid screen for amyloid cardiomyopathy in community cardiology settings where SPECT imaging is common.”
The radiotracer is currently being used in early-stage clinical evaluation to assess safety and efficacy in patients with cardiac amyloidosis and healthy subjects at the University of Tennessee School of Medicine in collaboration with Attralus, Inc. Data and insights from this study are expected to support future initiation of Phase 3 trials and submission for FDA approval.
Abstract 241277. “Preliminary Evaluation of 99mTc-Labeled Peptide p5+14 for Detection of Cardiopulmonary Amyloidosis Using SPECT/CT and Planar Gamma Scintigraphy 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 College of Medicine, Knoxville, TN.
