Assessment of cardiac autonomic neuronal function using PET imaging

The autonomic nervous system is the primary extrinsic control of cardiac performance, and altered autonomic activity has been recognized as an important factor in the progression of various cardiac pathologies. Molecular imaging techniques have been developed for global and regional interrogation of pre- and postsynaptic targets of the cardiac autonomic nervous system. Building on established work with the guanethidine analogue 123I-metaiodobenzylguanidine (MIBG) for single-photon emission tomography (SPECT), development of radiotracers and protocols for positron emission tomography (PET) investigation of autonomic signaling has expanded. PET is limited in availability and requires specialized centers for radiosynthesis and interpretation, but the higher resolution allows for improved regional analysis and kinetic modeling provides more true quantification than is possible with SPECT. A wider array of radiolabeled catecholamines, analogues of catecholamines, and receptor ligands have been characterized and evaluated. Sympathetic neuronal PET tracers have shown promise in the identification of several cardiac pathologies. In particular, recent studies have elucidated a mechanistic role for heterogeneous sympathetic innervation in the development of lethal ventricular arrhythmias. Evaluation of cardiomyocyte adrenergic receptor expression and the parasympathetic nervous system has been slower to develop, with clinical studies beginning to emerge. This review summarizes the clinical and the experimental PET tracers currently available for autonomic imaging and discusses their application in health and cardiovascular disease, with particular emphasis on the major findings of the last decade.