Preclinical and preliminary clinical evaluation of [¹⁸F]Florbetazine for non-invasive PET detection of cardiac amyloidosis.

Abstract

Early detection of cardiac amyloidosis (CA) remains challenging, and a PET tracer capable of directly visualizing amyloid deposits could improve diagnosis. Given the shared β-sheet structure of amyloid deposits in CA and Alzheimer's disease (AD), this study aimed to evaluate the suitability of the AD amyloid tracer [¹⁸F]Florbetazine for non-invasive detection of CA via preclinical assessments and preliminary clinical evaluation. Specific binding and affinity of [¹⁸F]Florbetazine to amyloid light-chain (AL) and transthyretin (ATTR) deposits were assessed via in vitro autoradiography on human myocardial sections. Pharmacokinetics and biodistribution were characterized by dynamic micro-PET/CT imaging in healthy Sprague Dawley (SD) rats. Whole-body PET/CT imaging was performed in two healthy volunteers to estimate normal-organ background, and in a single patient with biopsy-proven AL amyloidosis to preliminarily explore diagnostic feasibility. Autoradiography confirmed specific binding of [¹⁸F]Florbetazine to both AL and ATTR deposits with high binding affinities (K_d = 20.85 nM and 54.10 nM, respectively). In rats, [¹⁸F]Florbetazine exhibited rapid myocardial and renal uptake followed by efficient clearance from normal tissues. In healthy volunteers, background myocardium and renal activity was minimal by 40 min post-injection. In the AL amyloidosis patient, delayed-phase PET/CT imaging (60-70 min) revealed intense myocardium and renal uptake, correlating with renal biopsy findings. These integrated preclinical and preliminary clinical evaluation demonstrates that [¹⁸F]Florbetazine binds cardiac amyloid with high affinity and displays favorable pharmacokinetics, warranting further investigation in larger, systematically designed clinical studies. Clinical trial registry NCT06593626 (registered 24 May 2024) and NCT06725706 (registered 5 Dec 2024).