Cardiovascular PET Imaging for Early Disease Diagnosis
According to the American Heart Association, an estimated 82.6 million American adults have one or more types of cardiovascular disease (CVD). As the leading cause of death in the U.S., accounting for 1 in 6 deaths, the early detection of CVD is crucial to the diagnosis and treatment of the disease. Nuclear medical systems, such as positron emission tomography (PET), have long been used to visualize organs non-invasively. Cardiac nuclear medicine studies are aimed to help diagnose cardiac disease by using radiolabeled agents. Diagnostic imaging procedures allow physicians to visualize blood flow patterns to the heart walls and evaluate the presence and extent of suspected or known coronary artery disease. It also allows physicians to determine the extent of injury to the heart following a heart attack, or myocardial infarction, and evaluate the results of bypass surgery or other revascularization procedures designed to restore blood supply to the heart. These all play a crucial role in providing the best regimen to increase treatment response. Although nuclear imaging is non-invasive and provides a wealth of visual information for diagnostic purposes, radioisotopes can be harmful by causing radiation poisoning. It is, therefore, important to develop nuclear contrast agents that are effective at lower doses and released from the body within a reasonable amount of time.
Synthesis and Evaluation of Radiolabeled Contrast Agents
Researchers have established two separate methods to synthesize high yields of radiolabeled-fluorine phenethylguanidine, 4-[18F]fluoro-meta-hydroxy phenethylguanidine (4-[18F]-MHPG), from a diaryliodonium salt precursor (Figures 1 & 2). This compound was tested as a contrast agent for PET imaging. The researchers determined the kinetics behavior of 4-[18F]-MHPG in the isolated working rat heart model. Results demonstrate that 4-[18F]-MHPG has a long retention time inside sympathetic neurons (T1/2 > 24 hr), which will make tracer kinetic modeling of its myocardial kinetics in humans simpler and more robust than is currently possible with existing cardiac sympathetic nerve imaging agents. High-quality images show uniform left ventricular uptake of 4-[18F]-MHPG, with very low uptake of the compound in the lungs and liver. Studies were also performed to verify that presynaptic sympathetic nerve terminals are the main locus of retention of 4-[18F]-MHPG in the heart. The researchers also examined the uptake of 4-[18F]-MHPG into the adrenal gland, and results suggests that this agent could potentially find oncology applications in the nuclear medicine clinic as well.
Applications and Advantages
- Cardiovascular diagnostic imaging
- Adrenergic tumor detection
- High-yield synthesis
- Dual purpose
- Uniform left ventricular uptake, with low lung or liver uptake
- Long retention time inside sympathetic neurons
- Modeling of myocardial kinetics becomes simpler and more robust