Developing improved non-invasive imaging for assessing heart damage

Ex vivo scans of hearts from fibrotic (left) and control mice which were administered a unique fluorescent peptide that targets collagen type I. A striking enhancement of the damaged heart ventricles is observed. Image: Figure 5 in study

Cardiac fibrosis is a scarring process causing excess deposition of collagen in the heart, leading to distortion of its architecture and function. It is a significant disease feature in many cardiac conditions, including heart failure, atrial fibrillation (AF) and myocardial infarction (MI).

Current imaging techniques of cardiac fibrosis using Magnetic Resonance Imaging (MRI) suffer substantial limitations. Nevertheless, the use of clever imaging molecules that directly bind collagen could overcome these shortfalls and allow more sensitive detection of the fibrotic heart, resulting in earlier diagnosis and better treatment of heart disease.

A collaborative project, conducted at the Australian Centre for Blood Diseases (ACBD) by final-year doctoral student Martin Ezeani, under the supervision of Professor Christoph Hagemeyer and Dr Be'eri Niego from the NanoBiotechnology group, tested new peptide tracers that tightly bind various types of collagen and enable the delivery of imaging agents (such as near-infrared fluorophores and radioactive materials) to the affected heart.

A cross-institutional team provided essential expertise for the study, including chemists from Bio21 (Prof Paul Donnelly and Dr Asif Noor – a co-first author), a cardiologist (Dr Sean Lal from the University of Sydney) and Monash’s Dr Karen Alt, who heads the NanoTheranostics group at the ACBD.

Senior author Dr Niego said, "We successfully employed this novel molecular imaging approach to demonstrate diffuse cardiac fibrosis in a transgenic mouse model of heart disease (the β2-adrenergic receptor overexpressing mouse). This form of cardiac pathology is notably challenging to image by current medical imaging technologies. We further took an important step towards translation by showing that these peptide probes can enhance the fibrotic areas in diseased human cardiac tissue obtained from the Sydney Heart Bank.

"With encouraging results currently accumulating also in mouse models of MI and AF, using clinically-relevant imaging modalities like positron-emission tomography (PET), this exciting project is on track to yield clinically-compatible breakthroughs for the detection of heart fibrosis, with significant impacts on the management of cardiac patients."

Reference

Ezeani M, Noor A, Alt K, Lal S, Donnelly PS, Hagemeyer CE, Niego B. Collagen-Targeted Peptides for Molecular Imaging of Diffuse Cardiac Fibrosis. J Am Heart Assoc. 2021 Sep 13:e022139. doi: 10.1161/JAHA.121.022139. Epub ahead of print. PMID: 34514814.