Abstract
PurposeWe aim to provide an overview of the conventional single photon emission computed tomography (SPECT) and emerging positron emission tomography (PET) catecholamine analogue tracers for assessing myocardial nerve integrity, in particular focusing on 18F-labeled tracers.ResultsIncreasingly, the cardiac sympathetic nervous system (SNS) is being studied by non-invasive molecular imaging approaches. Forming the backbone of myocardial SNS imaging, the norepinephrine (NE) transporter at the sympathetic nerve terminal plays a crucial role for visualizing denervated myocardium: in particular, the single-photon-emitting NE analogue 123I-meta-Iodobenzylguanidine (123I-mIBG) has demonstrated favorable results in the identification of patients at a high risk for cardiac death. However, cardiac neuronal PET agents offer several advantages including improved spatio-temporal resolution and intrinsic quantifiability. Compared to their 11C-labeled counterparts with a short half-life (20.4 min), novel 18F-labeled PET imaging agents to assess myocardial nerve integrity have the potential to revolutionize the field of SNS molecular imaging. The longer half-life of 18F (109.8 min) allows for more flexibility in the study design and delivery from central cyclotron facilities to smaller hospitals may lead to further cost reduction. A great deal of progress has been made by the first in-human studies of such 18F-labeled SNS imaging agents. Moreover, dedicated animal platforms open avenues for further insights into the handling of radiolabeled catecholamine analogues at the sympathetic nerve terminal.Conclusions18F-labeled imaging agents demonstrate key properties for mapping cardiac sympathetic nerve integrity and might outperform current SPECT-based or 11C-labeled tracers in the long run.
Highlights
Heart failure (HF) is primarily characterized by a vicious cycle: myocardial injury leads to reduced cardiac output, which triggers myocardial sympathetic nervous system (SNS) hyperactivity, which in turn leads to further cardiac damage and to a further reduction of systolic function [1, 2]
In contradistinction to conventional imaging modalities, molecular imaging using either single photon emission computed tomography (SPECT) or positron-emission tomography (PET) offers the unique opportunity to characterize alterations on a subcellular level and to gain deeper insights into cardiac disease development and early onset of HF [10]: Physiologic NE is stored in presynaptic vesicles and once a firing impulse has arrived at the nerve terminal, NE is exocitotically released into the synaptic cleft, where it is readily available for interacting with postsynaptic adrenoreceptors
We provided an overview of the most commonly used SPECT and PET catecholamine analogue radiotracers for mapping myocardial nerve integrity. 123I-mIBG is considered to be the “Work Horse” in daily clinical routine [13] and multiple studies have demonstrated its benefit in different clinical scenarios
Summary
Heart failure (HF) is primarily characterized by a vicious cycle: myocardial injury leads to reduced cardiac output, which triggers myocardial sympathetic nervous system (SNS) hyperactivity, which in turn leads to further cardiac damage and to a further reduction of systolic function [1, 2]. Compared to its 11C-based counterpart, the 18F-labeled imaging agent demonstrated superior kinetics, in particular for early cardiac imaging [54] This phase-2 trial might pave the way for a phase-3 trial, which would further investigate the potential benefit of 18F-LMI1195 for risk stratification among HF patients. Taken up more slowly and demonstrated significantly longer neuronal retention times compared to 11C-HED or 11C-mIBG in isolated rat hearts, mainly due to efficient storage inside NE storage vesicles [55] Such key characteristics might be of utmost importance in kinetic analyses of regional nerve density assessment, as such radiotracers are capable of reflecting even modest alterations of cardiac sympathetic nerve conditions without being hampered by the blood flow effect. These compounds seem to have optimal kinetics and can allow for quantitative assessment of even a slight loss of cardiac sympathetic nerve density or regional denervation [44]
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