Monitoring of therapeutic effect in heart failure patients: a clinical application of 123I MIBG imaging?

Abstract

Labelling of metaiodobenzylguanidine (MIBG) with 123I allows scintigraphic visualization of the cardiac sympathetic nervous system and 123I MIBG was the first radiopharmaceutical that allowed imaging of cardiac neurotransmission by single photon emission computed tomography. Norepinephrine (NE) is the major neurotransmitter of the sympathetic nervous system. 123I MIBG, an analogue of NE, and NE have similar molecular structures, and use the same uptake and storage mechanisms in the pre-synaptic sympathetic nerve ending. Uptake-1 is the most important uptake mechanism of MIBG in human, and is sodium- and energy-dependent. Other uptake mechanisms are the non-neuronal uptake-2 mechanism, which is sodium- and energy-independent, and diffusion. The cardiac sympathetic nervous system is mainly involved in preserving circulatory homeostasis during environmental stress. Increase of sympathetic nervous activity or a rise in catecholamine levels result in cardiac adrenergic stimulation and has subsequent chronotropic (increase in heart rate), inotropic (increase in contractility), and dromotropic (enhanced atrioventricular conduction) effects. For the cardiovascular system in general, an increase in sympathetic nervous activity leads to an increase in peripheral vascular resistance, sodium and water retention, and activation of other neurohormonal systems. Although, in acute heart failure, these effects of enhanced sympathetic nervous activity are at first compensatory, prolonged hyperactivity of the sympathetic nervous system is supposed to be harmful in chronic heart failure. Vascular constriction and increased sodium and water retention will take its toll on energy demands of the myocardium. Furthermore, altered sympathetic cardiac adrenergic function may cause arrhythmias, desensitization of post-synaptic s-adrenoceptors, and activation of the renin–angiotensin system. Prolonged exposure to NE may … *Corresponding author. Tel: +31 71 526 2020; fax: +31 71 526 6809. E-mail address: e.e.van\_der\_wall{at}lumc.nl