Regional Distribution of Fluorine-18-Flubrobenguane and Carbon-11-Hydroxyephedrine for Cardiac PET Imaging of Sympathetic Innervation

Cardiac Sympathetic Positron Emission Tomography Imaging with Meta-[18F]Fluorobenzylguanidine is Sensitive to Uptake-1 in Rats

“…Given these attributes, [ 18 F]­mFBG may exhibit slower uptake into tissues, with distribution less dependent on tissue perfusion. This hypothesis is consistent with observable myocardial washout in [ 18 F]­mFBG human imaging, in contrast to the very slow washout kinetics that [ 123 I]­mIBG displays , and irreversible cardiac uptake of [ 11 C]­HED and [ 18 F]­FBBG . We were further attracted to [ 18 F]­mFBG by its potential for faster myocardial clearance and slower reuptake as it may provide critical information on the sympathetic tone and improvements in the quantification of neuronal dysfunction …”

“…This hypothesis is consistent with observable myocardial washout in [ 18 F]mFBG human imaging, 26 in contrast to the very slow washout kinetics that [ 123 I]mIBG displays 27,28 and irreversible cardiac uptake of [ 11 C]HED and [ 18 F]FBBG. 29 We were further attracted to [ 18 F]mFBG by its potential for faster myocardial clearance and slower reuptake as it may provide critical information on the sympathetic tone and improvements in the quantification of neuronal dysfunction. 29 However, because of synthetic challenges associated with radiofluorination of deactivated arenes, the development of this compound has been gradual, with a few recent reports demonstrating the utility of [ 18 F]mFBG for imaging neuroendocrine tumors.…”

“…29 We were further attracted to [ 18 F]mFBG by its potential for faster myocardial clearance and slower reuptake as it may provide critical information on the sympathetic tone and improvements in the quantification of neuronal dysfunction. 29 However, because of synthetic challenges associated with radiofluorination of deactivated arenes, the development of this compound has been gradual, with a few recent reports demonstrating the utility of [ 18 F]mFBG for imaging neuroendocrine tumors. 26,30 New syntheses have been reported using either copper-mediated radiofluorination or diaryliodonium salt precursors, both of which are accompanied by technical challenges related to automation and access to precursors.…”

Can the promise of radionuclide cardiac innervation imaging be fulfilled?

“…In addition, in contrast to SPECT, with PET, there is more potential to create tracers with varying uptake properties that can provide pathophysiologic detail of differing adrenergic innervation abnormalities. 16,17 PET cardiac adrenergic imaging has been studied for many years, mostly using 11 C-HED. The Prediction of Arrhythmic Events with Positron Emission Tomography (PARE-PET) study of 204 ischemic cardiomyopathic subjects with LVEF B 35%, undergoing 11 C-HED adrenergic imaging found that the % innervation shown by 11 C-HED imaging predicted 4-year occurrence of sudden cardiac arrest (SCA), while infarct volume, BNP, and LVEF did not.…”

“…While 11 C-HED is considered an excellent sympathetic innervation tracer, the need for an onsite or nearby cyclotron makes it impractical for most clinicians. More clinically feasible 18 F compounds are under active investigation, including 18 F-Flubrobenguane (FBBG, also known as 18 F-LMI-1195) 16 and the tracer F-18 meta-fluorobenzylguanidine ( 18 F-MFBG) investigated by Grkovski et al in this issue of the Journal of Nuclear Cardiology. 4 Based on the group's first-in-human phase-I study of 18 F-MFBG in patients with neuroblastoma and pheochromocytoma/paragangliomas showing safety and favorable biodistribution and kinetics with good targeting of neuroendocrine malignancies, 19 Grkovski et al performed concurrent dynamic and static 18 F-MFBG cardiac imaging in 16 of these patients with no known cardiac dysfunction, with 123 I-mIBG imaging also performed as part of standard of care.…”