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

PURPOSE: 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.

METHODS

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.

RESULTS

Autoradiography confirmed specific binding of [18F]Florbetazine to both AL and ATTR deposits with high binding affinities (Kd = 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.

CONCLUSIONS

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.

TRIAL REGISTRATION: Clinical trial registry NCT06593626 (registered 24 May 2024) and NCT06725706 (registered 5 Dec 2024).