Safety, Biodistribution, Dosimetry and Diagnostic Performance of [18F]FIDT-10b in Healthy Subjects and Patients With Cardiac Amyloidosis

Light chain cardiac amyloidosis (AL-CA) and transthyretin cardiac amyloidosis (ATTR-CA) are the two leading causes of cardiac amyloidosis with tremendous impact on patients. Regardless of the underlying cause, the clinical course of cardiac amyloidosis ultimately culminates in impaired cardiac function resulting from amyloid deposition, manifesting as infiltrative cardiomyopathy, conduction abnormalities, and cardiac sympathetic and parasympathetic denervation. These cardiac functional impairments are irreversible. Therefore, early etiological diagnosis and effective therapeutic intervention prior to the progress of severe cardiac dysfunction are importance.

There is an urgent need for non-invasive, sensitive, accurate, and visualizable approaches for the diagnosis and subtyping of cardiac amyloidosis. Current guidelines recommend bone scintigraphy for the non-invasive diagnosis of ATTR-CA, with a diagnostic specificity exceeding 90% but a sensitivity of only approximately 71%, raising the possibility of missed diagnosis or delayed diagnosis in a subset of patients. This has further propelled the development of PET molecular probes that specifically target amyloid proteins.

The investigators have preclinical data demonstrating that [18F]FIDT-10b selectively binds to ATTR deposits with high affinity in vitro via a combination of intermolecular forces, including van fer Waals forces, hydrophobic- hydrophobic interactions, π-π stacking, and hydrogen bonds, with the β-sheet architecture, supporting its potential utility for specific imaging of affected myocardium in patients with ATTR-CA. The investigators propose that this agent has significant potential for clinical translation. This first-in-human study is designed to evaluate the safety, pharmacokinetics, biodistribution in patients with cardiac amyloidosis and healthy participants (Part 1), and diagnostic performance of [18F]FIDT-10b in individuals with suspected or confirmed ATTR-CA (Part 2). This study will provide critical insights into the performance of [18F]FIDT-10b PET imaging as a potential non-invasive imaging tool for the detection of ATTR-CA and compared with routine clinical 99mTc-PYP SPECT imaging.