New PET Radiotracers

Rubidium-82 technology has established benchmarks in the assessment of myocardial perfusion against which the next generation of cardiac agents can be measured for sensitivity and specificity. It also is producing data that should demonstrate the cost-effectiveness of cardiac PET over SPECT, and has pioneered the way for cardiac PET through the issuance of CPT codes and reimbursement policy by third-party payers for PET myocardial perfusion. But rubidium-82 has drawbacks that may limit its sustained clinical adoption as seen in recent publications. These limitations include supply chain issues, economics, its short half-life and potential safety issues as presented in the black box warning in the package insert.  These issues should be resolved by the coming wave of new fluorinated cardiac PET radiopharmaceuticals.

Fluorinated positron emitters that compose the next generation of PET radiopharmaceuticals offer benefits over rubidium, including a longer half life of about 109 minutes. They also offer some clinical possibilities in the diagnosis and monitoring of cardiovascular disease beyond myocardial perfusion. Expected advantages of these new agents over SPECT radiopharmaceuticals are improved diagnostic accuracy, image clarity and lower radiation exposure to patients. 

Lantheus Medical Imaging’s Flurpiridaz F-18 myocardial perfusion imaging agent is currently being evaluated in Phase III clinical studies. The agent can be used with exercise stress (PET is currently limited by its short half-life agent to pharmaceutically induced stress), and has a high extraction rate of up to 90 percent by the mycardium, which can help reduce the amount of agent and the radiation dose to the patient. Also, F-18 tracers are already being produced and have an established distribution network.  

FluoroPharma’s BFPET, a fluorinated myocardial perfusion agent, exemplifies how the next generation of cardiac PET technology might boost diagnostic performance. In a study patient, BFPET indicated that the patient did not have a perfusion defect, as was suspected on the basis of SPECT, but rather suffered from apical thinning. Cardiovascular disease was confirmed through CT angiography — as was the absence of a perfusion defect.

BFPET has the potential to establish a new standard for measuring cardiovascular blood flow.  The agent is being developed for use in combination with stress testing in patients with presumptive chronic coronary artery disease (CAD), as a replacement for SPECT in institutions with PET capability. 

Healthcare reform emphasizes cost-effective care, so it is increasingly important to minimize the number of tests performed. The significance of getting it right the first time rises when considering the danger of cumulative radiation exposure to the patient, where the best diagnostic test done first might eliminate the need for subsequent invasive, expensive or unnecessary tests.

Several next-generation cardiac PET agents are designed to address unmet clinical needs. Whereas BFPET promises increased diagnostic accuracy compared with thallium and technetium-based SPECT agents, as well as advantages that go beyond the PET agent rubidium-82, CardioPET transcends even that, Spoor said. This agent, another in FluoroPharma’s pipeline, accesses a novel metabolic pathway, one that involves fatty acids, the primary source of energy for the cardiac muscle.

“Our studies indicate that imaging with CardioPET can potentially be used to accurately gauge fatty acid uptake by the myocardium. This uptake can be visualized and quantified using PET scanners that are becoming more available at price points within the grasp of routine practitioners,“ Spoor explained.

Preliminary data indicates that the agent is especially suited for the diagnosis of acute coronary syndrome and chronic coronary artery disease in patients who cannot undergo stress testing. 

By obtaining list-mode data on modern scanners, CardioPET may allow measurements of perfusion during the first five minutes of administration while scans done 40 to 60 minutes later may indicate tissue viability. These two clinical capabilities suggest the potential utility of CardioPET as a way to assess patients after they have complained of chest pain in the emergency department. 

PET may offer an imaging option to detect heart failure and the risk of sudden cardiac death by imaging the sympathetic nervous system using the cardiac neuronal agent LMI 1195. Lantheus has this agent in a Phase I trial.

Research is ongoing for use of FDG F-18 agents to image cardiac sarcoid to identify patients at risk for sudden death. “We see huge promise to inject these patients with FDG to check for sarcoid, and if they have it, we can get them treated with an ICD [implantable cardioverter defibrilator] before they end up in a fatal sitaution,” said April Mann, CNMT, NCT, FSNMMI-TS, manager of noninvasive cardiology, Hartford Hospital, during a presentation at SNMMI 2013.

Another exciting area of research mentioned by several SNMMI presenters is the use of coronary flow reserve as a way to quantify the severity of coronary lesions, similar to fractional flow reserve (FFR) measurements made invasively in the cath lab. F-18 agents may offer the best imaging agent for this type of quantification due to its high myocardial uptake and eliminate the need for diagnostic catheterizations.