title: The next generation of cardiac positron emission tomography imaging agents: discovery of flurpiridaz F-18 for detection of coronary disease.
abstract: Myocardial perfusion imaging (MPI) with thallium 201 ((201)Tl) or (99m)Tc based imaging agents has become a major tool for noninvasive identification of coronary artery disease (CAD). However, single photon emission computed tomography (SPECT) imaging with the current agents is vulnerable to artifacts associated with soft tissue attenuation, proximal gastrointestinal activity, image quality, and suboptimal sensitivity and is limited by the degree of first-pass myocardial extraction. The development of (18)F-based flurpiridaz F-18 takes advantage of positron emission tomography (PET) to overcome many of the imaging issues and structural design to achieve an ideal MPI agent profile. Flurpiridaz F-18 was designed to bind to mitochondrial complex I with high affinity and demonstrates high heart uptake in multiple species with clear delineation of perfusion deficits. It exhibits rapid uptake in the myocardium, prolonged retention, and superior extraction versus flow profiles compared with (201)Tl and (99m)Tc-sestamibi. A first in man study has established the safety and dosimetry of flurpiridaz F-18 and confirmed high sustained cardiac uptake. Subsequent studies performed in CAD patients established the dose and timing needed to detect perfusion deficits when the agent is administered under rest and stress conditions. This review compares the current preclinical and clinical data with an ideal MPI agent profile. The assessment indicates flurpiridaz F-18 represents a new generation of PET MPI agents and demonstrates significantly improved molecular and imaging characteristics.
authors.affiliation: Discovery Research, Lantheus Medical Imaging, N Billerica, MA, USA. ming.yu@lantheus.com
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Stephan G
authors.initials: SG
authors.lastname: Nekolla
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.forename: Simon P
authors.initials: SP
authors.lastname: Robinson
mesh_terms: D000818:Animals; D003327:Coronary Disease / Q000000981:diagnostic imaging*; D042967:Electron Transport Complex I / Q000378:metabolism; D006321:Heart / Q000000981:diagnostic imaging / Q000502:physiology; D006801:Humans; D055414:Myocardial Perfusion Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D011323:Primates; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D018570:Risk Assessment; D013552:Swine; D014018:Tissue Distribution
chemical_list: C525920:BMS 747158-02; D011724:Pyridazines; D019275:Radiopharmaceuticals; D042967:Electron Transport Complex I