[Advances in Cardiac Sympathetic PET Imaging: Development and Clinical Translation of 18F-fluproxadine (18F-AF78)].

The cardiac sympathetic nervous system plays an important role in the pathophysiology and prognosis of heart failure, ischemic heart disease, and arrhythmias. Cardiac sympathetic innervation has traditionally been assessed using 123I-meta-iodobenzylguanidine (123I-MIBG) SPECT and 11C-hydroxyephedrine (11C-HED) PET. However, these approaches have limitations related to spatial resolution, quantitative capability, physical half-life, and dependence on specialized facilities. 18F-fluproxadine, formerly known as 18F-AF78, is a novel PET tracer targeting the norepinephrine transporter (NET) at sympathetic nerve terminals. Preclinical studies have demonstrated its high NET affinity, favorable myocardial uptake, and potential to reflect intravesicular neuronal dynamics. In addition, structure-activity relationship analyses, investigations of interactions with organic cation transporters (OCTs), development of a clinical radiosynthesis method, and First-in-Human evaluation have provided a foundation for clinical translation. This review summarizes the development of 18F-fluproxadine PET and discusses future perspectives for cardiac sympathetic nerve imaging.