PET imaging for myocardial innervation expands with F-18 labeled agent

First-in-human study of an investigational radiotracer, F-18 LMI1195, shows clear imaging of myocardial innervation via the norepinephrine transporter system—tipping off potential adverse cardiac events, according to a study published July 3 in the Journal of Nuclear Medicine.

Heart failure (HF) and sudden cardiac death (SCD) are linked to abnormalities of the cardiac sympathetic nervous system. Changes associated with these abnormalities include increased norepinephrine release from cardiac sympathetic nerves and a decrease in cardiac norepinephrine reuptake. Norepinephrine transporter imaging with F-18 LMI1195, full name (N-[3-bromo-4-(3-18F-fluoro-propoxy)-benzyl]-guanidine [LMI1195], could provide a visual map of these changes.

Albert J. Sinusas, from the cardiovascular section of the department of medicine at Yale University School of Medicine in New Haven, Conn., and colleagues conducted the trial to determine biodistribution and radiation dosimetry for the novel agent in 12 healthy participants who underwent PET imaging with F-18 LMI1195 in three clinical sites.

“This phase I, multicenter, non-randomized, single-dose, open-label, first-in-human clinical trial of LMI1195, a new PET imaging agent for the noninvasive assessment of sympathetic activity, demonstrates no safety concerns, rapid blood clearance, and extraction by the heart with stable myocardial activity over five hours and a favorable biodistribution for cardiac imaging over the same period of time,” wrote Sinusas et al.

Currently SPECT with I-123 metaiodobenzylguanidine (I-123 MIBG) is the molecular imaging standard for myocardial innervation. F-18 LMI1195 is in the same class as MIBG, but allows for PET imaging with a longer half-life than C-11 metahydroxyephedrine. Previous preclinical studies showed that F-18 LMI1195 was superior to MIBG.

“Although PET imaging offers advantages over SPECT imaging for quantification of regional and global myocardial activity, PET sympathetic imaging agents have been principally C-11 labeled, limiting widespread clinical translation of this approach. The availability of an F-18 labeled sympathetic agent such as LMI1195 could open the door for large multicenter PET-based imaging trials of sympathetic activation in the setting of infarction or congestive HF for prediction of SCD.”

Further multi-center trials and comparison studies are needed to fully understand the value of LMI1195 and how it compares to MIBG for sympathetic imaging.