New radiotracer yields high-quality images of 'heart Alzheimer's'

A groundbreaking imaging agent, known as 99mTc-p5+14, has been developed to produce clear and easily interpretable images of cardiac amyloidosis – a condition often dubbed the "Alzheimer's disease of the heart." This innovative radiotracer is the first of its kind specifically designed for planar and SPECT/CT imaging, and it holds significant promise for the early detection and management of cardiac amyloidosis. The details of this research were unveiled at the 2024 Society of Nuclear Medicine and Molecular Imaging Annual Meeting.

Cardiac amyloidosis is part of a broader group of diseases known as systemic amyloidosis, where abnormal protein deposits accumulate in tissues and organs. This incurable condition is particularly deadly when it affects the heart, with around 20% of patients experiencing early death. Despite advancements in treatment, the median survival for patients with cardiac amyloidosis remains bleak, typically ranging from three to five years.

Jonathan Wall, PhD, director of the Amyloidosis and Cancer Theranostics Program at the University of Tennessee Graduate School of Medicine, emphasized the critical need for early detection. "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," he said. Wall also pointed out the current lack of FDA-approved imaging agents for detecting this condition.

In response to this significant gap, researchers created the technetium-99m labeled version of the pan-amyloid reactive peptide p5+14 (99mTc-p5+14). In a pioneering first-in-human study, 35 participants, including five healthy volunteers and 30 newly diagnosed patients with light chain or transthyretin amyloidosis, underwent imaging using 99mTc-p5+14 with standard planar gamma scintigraphy and SPECT/CT. The study also included blood tests to measure serum biomarkers and transthoracic echocardiograms. Most patients also received a standard 99mTc-pyrophosphate imaging session 72 hours post 99mTc-p5+14 imaging.

The results were promising, showing that images obtained using 99mTc-p5+14 were of high quality and easily interpretable at both one and three hours post-injection. Significant 99mTc-p5+14 uptake was observed in the hearts of patients with amyloid cardiomyopathy, while healthy subjects showed no such uptake.

"Early and accurate diagnosis of cardiac amyloidosis is crucial to ensure the most positive outcomes for patients," Wall noted. He added that 99mTc-p5+14 imaging could become a straightforward and easily interpretable technology for community cardiology settings, where SPECT imaging is commonly available. This could serve as a rapid screening tool for amyloid cardiomyopathy in the future.

Currently, the 99mTc-p5+14 radiotracer is undergoing early-stage clinical evaluation at the University of Tennessee Graduate School of Medicine, in collaboration with Attralus Inc. The aim is to assess its safety and efficacy in both patients with cardiac amyloidosis and healthy subjects. The insights gained from this research are expected to support a pivotal Phase 3 study and subsequent FDA approval submissions in the forthcoming years.

The study, titled "Preliminary Evaluation of 99mTc-Labeled Peptide p5+14 for the Detection of Cardiopulmonary Amyloidosis Using SPECT/CT and Planar Gamma Scintigraphic Imaging," was conducted by a team of researchers including Jonathan Wall, Emily Martin, Alan Stuckey, and others from the University of Tennessee Graduate School of Medicine.