Recent Advances and Clinical Applications of PET Cardiac Autonomic Nervous System Imaging

Abstract

Purpose of Review The purpose of this review was to summarize current advances in positron emission tomography (PET) cardiac autonomic nervous system (ANS) imaging, with a specific focus on clinical applications of novel and established tracers. Recent Findings [11C]-Meta-hydroxyephedrine (HED) has provided useful information in evaluation of normal and pathological cardiovascular function. Recently, [11C]-HED PET imaging was able to predict lethal arrhythmias, sudden cardiac death (SCD), and all-cause mortality in heart failure patients with reduced ejection fraction (HFrEF). In addition, initial [11C]-HED PET imaging studies have shown the potential of this agent in elucidating the relationship between impaired cardiac sympathetic nervous system (SNS) innervation and the severity of diastolic dysfunction in HF patients with preserved ejection fraction (HFpEF) and in predicting the response to cardiac resynchronization therapy (CRT) in HFrEF patients. Longer half-life 18F-labeled presynaptic SNS tracers (e.g., [18F]-LMI1195) have been developed to facilitate clinical imaging, although no PET radiotracers that target the ANS have gained wide clinical use in the cardiovascular system. Although the use of parasympathetic nervous system radiotracers in cardiac imaging is limited, the novel tracer, [11C]-donepezil, has shown potential utility in initial studies. Summary Many ANS radioligands have been synthesized for PET cardiac imaging, but to date, the most clinically relevant PET tracer has been [11C]-HED. Recent studies have shown the utility of [11C]-HED in relevant clinical issues, such as in the elusive clinical syndrome of HFpEF. Conversely, tracers that target cardiac PNS innervation have been used less clinically, but novel tracers show potential utility for future work. The future application of [11C]-HED and newly designed 18F-labeled tracers for targeting the ANS hold promise for the evaluation and management of a wide range of cardiovascular diseases, including the prognostication of patients with HFpEF.

Current State and Future Technologies of Nuclear Imaging in Cardiology

“…Для определения плотности симпатических окончаний используют радиоактивные аналоги катехоламинов -123 I-метайодбензилгуанидин ( 123 I-MИБГ) для сцинтиграфии и ОЭКТ миокарда, 11 C-гидроксиэфедрин ( 11 C-HED), 18 F-6-фтордофамин ( 18 F-6-FDA), 18 F-6-фторнорадреналин ( 18 F-6-FNE), 11 C-адреналин ( 11 C-EPI), 18 F-6-фтор-метараминол ( 18 F-6-FMR), 11 C-фенилэфрин ( 11 C-PHEN), 11 C-CGP-12177 для исследований методом ПЭТ [41]. Имеется ряд экспериментальных РФП для оценки состояния парасимпатической части вегетативной нервной системы сердца [42]. Основные клинические задачи практического применения этих РФПоценка тяжести и прогноза сердечной недостаточности, а также возможности поиска потенциально фатальных зон аритмогенеза, в частности, при планировании установки кардиовертера-дефибриллятора.…”

Reaction of 11C‐benzoyl chlorides with metalloid reagents: 11C‐labeling of benzyl alcohols, benzaldehydes, and phenyl ketones from [11C]CO

“…PET is a non-invasive imaging modality in which physiological and biochemical processes can be studied in vivo following the intravenous administration of a radiolabeled bioactive compound called radiotracer. 1,2 PET is frequently being used in cardiology, 3 neurology, 4 as well as oncology, 5 and more recently has proven to be a valuable technique in drug discovery. 6,7 The abundance of carbon in organic molecules makes carbon-11 (t 1/2 = 20.4 minutes) an appealing isotope for PET radiotracer development.…”

Dynamic cardiac PET imaging: Technological improvements advancing future cardiac health

“…27 PET is ideal for researching and diagnosing the autonomic nervous system because of the ability to image the numerous 11 C-tagged pre-and post-synaptic radiotracers, developed over the last 25 years, capable of distinguishing subcellular catecholamine dysfunction from complete denervation of cardiac sympathetic and parasympathetic innervation. 28,29 The FDA has approved the SPECT tracer 123 I-MIBG for evaluation of those patients with Class II-III congestive heart failure (CHF) and LVEF\35%. 30 MIBG is an analog of the false neurotransmitter guanethidine taken up by adrenergic neurons of the cardiac sympathetic nervous system, similar to norepinephrine and allows a unique characterization of alterations in cardiac regional sympathetic nerve function.…”

“…Comparable results using the analogous PET agent 11 Cmeta-hydroxyephedrine ( 11 C-HED) have been reported, where PET imaging in HF patients with preserved ejection fraction (HFpEF) has been able to predict lethal arrhythmias, sudden cardiac death, response to cardiac resynchronization therapy, and relate severity of diastolic dysfunction to impaired cardiac sympathetic nervous system innervation. 28,29 The longer half-life tracers, such as 18 F-LMI1195, has similar tracer kinetics to 123 I-MIBG and would be a preferred PET radiotracer to image the autonomic nervous system. 32 The use of PET to image the cardiac parasympathetic nervous system radiotracers is limited; however, 11 C-donepezil a reversible antagonist of acetylcholine, has shown potential efficacy in initial studies.…”

“…32 The use of PET to image the cardiac parasympathetic nervous system radiotracers is limited; however, 11 C-donepezil a reversible antagonist of acetylcholine, has shown potential efficacy in initial studies. 29 Dynamic PET imaging of glucose metabolism, fatty acid metabolism, and oxygen utilization provides information about metabolic shifts related to function, 33 making PET an outstanding tool in conjunction with MRI for measuring cardiac efficiency. 34 The three main metabolic substrates of the heart are carbohydrates, fatty acids, and ketone bodies with exogenous fatty acids accounting for 60%-70% of the energy production in the normal heart.…”