Research Progress on 18F-Labeled Agents for Imaging of Myocardial Perfusion with Positron Emission Tomography

Abstract

Coronary artery disease (CAD) is the leading cause of death in the world. Myocardial perfusion imaging (MPI) plays a significant role in non-invasive diagnosis and prognosis of CAD. However, neither single-photon emission computed tomography nor positron emission tomography clinical MPI agents can absolutely satisfy the demands of clinical practice. In the past decades, tremendous developments happened in the field of 18F-labeled MPI tracers. This review summarizes the current state of 18F-labeled MPI tracers, basic research data of those tracers, and the future direction of MPI tracer research.

Development and preclinical evaluation of novel fluorinated ammonium salts for PET myocardial perfusion imaging

“…The availability of a suitable fluorine-18 labeled pharmaceutical is expected to enhance the use of PET for MPI due to its ideal imaging properties and convenient half-life (~ 110 min), which allows distribution to remote sites. Numerous 18 F-labeled pharmaceuticals have been investigated for potential PET-MPI use 6 . The most promising agent thus far, [ 18 F]flurpiridaz, is currently under a second phase-3 clinical trial, which is predicted to be completed by the end of 2021 7 .…”

Synthesis, gallium-68 radiolabelling and biological evaluation of a series of triarylphosphonium-functionalized DO3A chelators

“…TPP is widely known to target mitochondria since the cationic charge nominally residing on the phosphorus atom can be delocalised around the aromatic rings. 3,4,17,18 The first PET tracer to utilise TPP was designed by Fukuda et al and consisted of TPP methylated with carbon-11 (methylTPP). 19 Since then, there have been many different types of TPP-functionalised PET tracers for mitochondrial imaging, most commonly using fluorine-18 since its longer half-life facilitates clinical imaging.…”

Synthesis and ex vivo biological evaluation of gallium-68 labelled NODAGA chelates assessing cardiac uptake and retention

“…Lipophilic triphenylphosphonium (TPP)functionalised compounds are also capable of targeting the mitochondria due to their delocalised positive charge across the large surface area of the aromatic rings, and TPP-based PET tracers radiolabelled with carbon-11 and fluorine-18 (t½ = 20 and 109.7 min respectively) have been extensively explored for mitochondrial imaging. [9][10][11][12][13][14][15][16][17][18] In 2014, Haslop et al synthesised a series of fluorine-18 radiolabelled compounds, [ 18 F]MitoPhos (Fig. 1), consisting of alkyl-functionalised motifs on triarylphosphonium (TAP) moieties, achieved via a coppercatalysed click reaction of an 18 F synthon to the TAP cation.…”

“…[9][10][11][12][13][14][15][16][17][18] In 2014, Haslop et al synthesised a series of fluorine-18 radiolabelled compounds, [ 18 F]MitoPhos (Fig. 1), consisting of alkyl-functionalised motifs on triarylphosphonium (TAP) moieties, achieved via a coppercatalysed click reaction of an 18 F synthon to the TAP cation. 19 Functionalisation of the TAP moiety afforded the tuneability of radiotracer lipophilicity which facilitated the modification of its Fig.…”