ACC Feature: New F18 tracer for heart failure shows preclinical promise

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ATLANTA—A novel cardiac PET tracer that images the sympathetic nervous system for heart failure prognosis has been shown in preclinical studies to provide improved image quality compared with a SPECT heart failure tracer, according to a poster presentation on display Monday at the American College of Cardiology conference.

SPECT imaging with 123I-MIBG was reported to have prognostic value in heart failure (HF), but the image quality was poor. LMI1195 (Lantheus Medical Imaging) is a newly developed imaging agent labeled with 18F to take technical advantages of PET over SPECT. Like 123I-MIBG, LMI1195 was designed as a substrate of the norepinephrine transporter, according to investigators, led by Ming Yu, MD, PhD, senior research investigator at Lantheus Medical.

Yu and colleagues assessed LMI1195 in cell membrane and human neuroblastoma cells with high expression of norepinephrine transporters, and in various animal species including non-human primates.

“In heart failure, the heart has to beat harder and faster, which results in changes to the sympathetic nervous system, primarily the reduction of norepinephrine transporters,” Yu told Cardiovascular Business News. In theory, the more damage to the heart, the less uptake of the LMI1195.

Patients with HF are susceptible to sudden cardiac death brought about because of arrhythmias. Studies have indicated that imaging the sympathetic nervous system in these patients can help predict who is more at risk and who should be given an implantable cardioverter-defibrillator (ICD), Simon Robinson, PhD, vice president, research and pharmaceutical development at Lantheus, told Cardiovascular Business News.

Compared with PET agents, such as carbon-11 hydroxyephedrine (C-11 HED), LMI1195 is an F18-labeled tracer, which has advantages in terms of half-life and deliverability because there is an infrastructure in the U.S. to regionally produce F18 analogues, Robinson said.

In the study, researchers showed that LMI1195 has good affinity to the norepinephrine transporters in cells and cell membranes. In addition, “uptake in the heart was very high and imaging quality was much better than current imaging agents, with very low background uptake in liver,” Yu said. “Our agent has high specificity to the target.”

In the animal studies, the agent followed the progression of HF, which “indicates this agent could be used for prognosis of HF progression and HF stratification,” Yu said.

The SCD-HeFT study showed that one in five patients that receive an ICD does not need it. “An agent such as LMI1195 could help physicians better identify those who would benefit most from an ICD,” Robinson said.

Lantheus hopes to present phase 1 data at the SNM meeting in Salt Lake City, scheduled for June.