Imaging cardiac voltage gated sodium channels using the novel F-18 radiotracer radiocaine

Myocardial contraction is controlled by an electro-mechanical coupling and cardiac action potentials that propagate across the heart. These action potentials are initiated by NaV1.5 voltage gated sodium channels. The role of cardiac NaV1.5 in cardiac disease is reasonably well understood in animal and in vitro models. However, linking changes in NaV1.5 expression levels to human disease in vivo has not yet been possible. “Radiocaine”, an F-18 radiotracer for positron emission tomography (PET), is the first NaV imaging agent in the heart. Explants from healthy and failing human hearts were compared using radiocaine autoradiography to determine that the failing heart had ~30% lower NaV1.5 levels - the first evidence of changes in cardiac NaV expression in humans as a function of disease. Paving the way for translational imaging, radiocaine proved to exhibit high in vivo specific binding to the myocardium of rats and non-human primates. We envision that NaV1.5 measurements using PET imaging may serve not onl...