Emerging Tracers for Nuclear Cardiac PET Imaging

Abstract

Myocardial perfusion imaging using positron emission tomography (PET) has several advantages over single photon emission computed tomography (SPECT). The recent advances in SPECT technology have shown promise, but there is still a large need for PET in the clinical management of coronary artery disease (CAD). Especially, absolute quantification of myocardial blood flow (MBF) using PET is extremely important. In spite of considerable advances in the diagnosis of CAD, novel PET radiopharmaceuticals remain necessary for the diagnosis of CAD because clinical use of current cardiac radiotracers is limited by their physical characteristics, such as decay mode, emission energy, and half-life. Thus, the use of a radioisotope that has proper characteristics and a proper half-life to develop myocardial perfusion agents could overcome these limitations. In this review, the current state of cardiac PET and a general overview of novel F orGa-labeled radiotracers, including their radiosynthesis, in vivo characterization, and evaluation, are provided. The future perspectives are discussed in terms of their potential usefulness based on new image analysis methods and hybrid imaging.

Development of Mitochondria-Targeted Small-Molecule Dyes for Myocardial PET and Fluorescence Bimodal Imaging

“…The results indicated that 5MEF specifically targeted mitochondria in cardiomyocytes and achieved much stronger fluorescence intensity than normal cells. These data suggest that 5MEF may be a promising probe for assessment of myocardial mitochondrial dysfunction. ,, …”

“…These data suggest that 5MEF may be a promising probe for assessment of myocardial mitochondrial dysfunction. 16,17,35 Animal Fluorescence Imaging. Ex vivo fluorescence imaging of 14 F16s was performed for tissues harvested from BALB/c mice at 2 h post injection of the probes.…”

“…43 Moreover, lipophilicity of these radiotracers could control myocardial selectivity and hepatic clearance. 17 Thus, controlling the lipophilicity and structural modification of the probe may be a potential way to increase myocardial uptake and liver clearance.…”

“…14,15 Recently, some 18 F-labeled probes based on the lipophilic phosphine cations, for example, triphenylphosphine (TPP), have been reported. 16,17,35 They show similar properties to 99m Tc-sestamibi and 99m Tctetrofosmin, which specifically accumulate and remain in the mitochondria-rich myocardium. However, most of these TPPbased 18 F-probes show a high background in normal tissues and a high activity uptake in bones because of defluorination, which would affect the accurate diagnosis of myocardial abnormalities.…”

“…However, SPECT has certain limitations such as relatively low spatial resolution and detection efficiency, poor sensitivity and specificity, and poor quantitative imaging capability. − Compared with SPECT, PET has advantages such as improved spatial resolution, higher sensitivity, lower tissue attenuation, and absolute quantification of myocardial blood flow (MBF). , However, the currently available myocardial PET probes such as 13 N–NH 3 ( t 1/2 = 9.97 min), 82 Rb ( t 1/2 = 1.27 min), and 15 O–H 2 O ( t 1/2 = 2.04 min) have an extremely short decay half-life, which limits the widespread clinical use because of the need for a costly cyclotron or generator . Notably, 18 F may overcome these limitations with a longer half-life (109.77 min), which allows for physical exercise stress and rest imaging. , Recently, some 18 F-labeled probes based on the lipophilic phosphine cations, for example, triphenylphosphine (TPP), have been reported. ,, They show similar properties to 99m Tc-sestamibi and 99m Tc-tetrofosmin, which specifically accumulate and remain in the mitochondria-rich myocardium. However, most of these TPP-based 18 F-probes show a high background in normal tissues and a high activity uptake in bones because of defluorination, which would affect the accurate diagnosis of myocardial abnormalities. , More importantly, reports on myocardial mitochondria-targeted lipophilic cation probes with both PET and fluorescence imaging capability are rare.…”