LAUSR

The myocardial sympathetic innervation plays a pivotal role in the progression of heart failure and in the occurrence of lifethreatening arrhythmias. An impaired function of presynaptic sympathetic nerve terminals is considered to reflect impaired reuptake and thus impaired removal of the neurotransmitter from the synaptic cleft [1], resulting in overexposure of the myocardium to catecholamines and in a pre/post-synaptic signaling imbalance [2]. Consistent with this pathophysiologic model, prospective, large-scale clinical trials confirmed an excellent prognostic value of adrenergic imaging in patients with heart failure, both with single photon emission tomography (SPECT) and with positron emission tomography (PET) [3, 4]. Although extensively validated and embedded in clinical practice, the study of myocardial sympathetic innervation activity with standard SPECT suffers from evident limitations. In fact, its main prognostic parameters, i.e., the heart-tomediastinum ratio and the cardiac washout rate, are generally derived from planar scans of the chest, thus allowing only for a semiquantitative evaluation of the global activity of sympathetic innervation. But as underlined also by a recent report, the heterogeneity of innervation may be more prognostically relevant than the assessment of the degree of sympathetic denervation [5]. As such, an imaging modality able to allow for a regional assessment of myocardial sympathetic innervation would be highly desirable. In this regard, new heart dedicated camera systems equipped with cadmium-zinc-telluride (CZT) solidstate detectors may constitute a valid alternative. Owing to improved image quality and temporal and spatial resolution over standard SPECT, a regional assessment of sympathetic innervation activity is feasible and accurate [6, 7]. Unfortunately, despite its great advantages, this novel, recently available SPECT technology is not widely deployed yet. Hence, PET may be a preferred technique for the assessment of the cardiac sympathetic nervous system, able to yield a significantly higher impact on clinical practice. PET provides superior sensitivity and resolution over conventional nuclear imaging, thus allowing for a precise localization of innervation defects. To date, themain limitation of PET relates in the need of an on-site cyclotron, which is required to produce C–labeled radiotracers such as Chydroxyephedrine (HED) for the study of the sympathetic innervation activity. Implementing F–labeled tracers would, therefore, be essential for awider dissemination of PET imaging in clinical practice. In this issue of the Journal, Kobayashi and co-workers report on new promising F–labeled PET radiopharmaceuticals targeting the sympathetic nervous system [8]. Similarly to what was already established for F–FDG, the improved cost-effectiveness of the dispatch of fluorinated tracers from central cyclotron facilities is expected to enhance the diffusion of PET-based sympathetic innervation imaging. Of the new tracers, a phase-1 trial on 12 healthy subjects reported a favorable biodistribution for F–LMI1195, similar to that of metaiodobenzylguanidine (MIBG), as well as an acceptable radiation dose. These characteristics are conceivably expected to make this radiocompound the first choice for an easy implementation in clinical practice. Even more interestingly, another two radiopharmaceuticals, i.e., F–4F-MHPG and F–3F-PHPG, were proven in animal models to yield accurate quantitative measures of regional nerve density along with a favorable heart-to-liver ratio. This Editorial Commentary refers to the article: Higuchi et al. BNew horizons in cardiac innervation imaging: introduction of novel F-labeled PET tracers^. https://doi.org/10.1007/s00259-017-3828-8