The lack of pediatrics-specific equipment for nuclear medicine imaging has resulted in insufficient diagnostic information for newborns, especially low-birth-weight infants. Although PET offers high spatial resolution and low radiation exposure, its use in newborns is limited. This study investigated the feasibility of cardiac PET imaging using the latest silicon photomultiplier (SiPM) PET technology in infants of extremely low birth weight (ELBW) using a phantom model. Methods: The study used a phantom model representing a 500-g ELBW infant with brain, cardiac, liver, and lung tissues. The cardiac tissue included a 3-mm-thick defect mimicking myocardial infarction. Organ tracer concentrations were calculated assuming 18F-FDG myocardial viability scans and 18F-flurpiridaz myocardial perfusion scans and were added to the phantom organs. Imaging was performed using an SiPM PET/CT scanner with a 5-min acquisition. The data acquired in list mode were reconstructed using 3-dimensional ordered-subsets expectation maximization with varying iterations. Image evaluation was based on the depiction of the myocardial defect compared with normal myocardial accumulation. Results: Increasing the number of iterations improved the contrast of the myocardial defect for both tracers, with 18F-flurpiridaz showing higher contrast than 18F-FDG. However, even at 50 iterations, both tracers overestimated the defect accumulation. A bull\'s-eye image can display the flow metabolism mismatch using images from both tracers. Conclusion: SiPM PET enabled cardiac PET imaging in a 500-g ELBW phantom with a 1-g heart. However, there were limitations in adequately depicting these defects. Considering the image quality and defect contrast,18F-flurpiridaz appears more desirable than 18F-FDG if only one of the two can be used.

18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) represent emerging PET tracers used to assess atherosclerosis-related inflammation and molecular calcification, respectively. By localizing to sites with high glucose utilization, FDG has been used to assess myocardial viability for decades, and its role in evaluating cardiac sarcoidosis has come to represent a major application. In addition to determining late-stage changes such as loss of perfusion or viability, by targeting mechanisms present in atherosclerosis, PET-based techniques have the ability to characterize atherogenesis in the early stages to guide intervention. Although it was once thought that FDG would be a reliable indicator of ongoing plaque formation, micro-calcification as portrayed by NaF-PET/CT appears to be a superior method of monitoring disease progression. PET imaging with NaF has the additional advantage of being able to determine abnormal uptake due to coronary artery disease, which is obscured by physiologic myocardial activity on FDG-PET/CT. In this review, we discuss the evolving roles of FDG, NaF, and other PET tracers in cardiac molecular imaging.

Myocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. 18F-flurpiridaz was recently introduced as a valid alternative to currently used PET-MPI probes. Nonetheless, optimum scan duration and time interval for image analysis are currently unknown. Further, it is unclear whether rest/stress PET-MPI with 18F-flurpiridaz is feasible in mice.
Rest/stress PET-MPI was performed with 18F-flurpiridaz (0.6-3.0 MBq) in 27 mice aged 7-8 months. Regadenoson (0.1 µg/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial 18F-flurpiridaz uptake was assessed for different time intervals by placing a volume of interest in the left ventricular myocardium.
Tracer kinetics were best described by a two-tissue compartment model. K1 ranged from 6.7 to 20.0 mL·cm-3·min-1, while myocardial volumes of distribution (VT) were between 34.6 and 83.6 mL·cm-3. Of note, myocardial 18F-flurpiridaz uptake (%ID/g) was significantly correlated with K1 at rest and following pharmacological vasodilation for all time intervals assessed. However, while Spearman\'s coefficients (rs) ranged between 0.478 and 0.681, R2 values were generally low. In contrast, an excellent correlation of myocardial 18F-flurpiridaz uptake with VT was obtained, particularly when employing the averaged myocardial uptake from 20 to 40 min post tracer injection (R2 ≥ 0.98). Notably, K1 and VT were similarly sensitive to pharmacological vasodilation induction. Further, mean stress-to-rest ratios of K1, VT, and %ID/g 18F-flurpiridaz were virtually identical, suggesting that %ID/g 18F-flurpiridaz can be used to estimate coronary flow reserve (CFR) in mice.
Our findings suggest that a simplified assessment of relative myocardial perfusion and CFR, based on image-derived tracer uptake, is feasible with 18F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents.

To comparatively explore the differences between 18F-Flurpiridaz and 13N-NH3·H2O PET/CT myocardial perfusion imaging in miniature pigs.
Ten Bama minipigs were divided into normal group and myocardial infarction group. The changes of the ratio of left ventricular myocardium to main organs with time were calculated and the best imaging time was confirmed for 18F-Flurpiridaz imaging in normal group. The image quality score, summed rest score(SRS), Extend, total perfusion deficit(TPD) and left ventricle ejection fraction(LVEF) were respectively compared for 18F-Flurpiridaz and 13N-NH3·H2O in infarction group.
18F-Flurpiridaz was rapid distributed in myocardium, and the background counts of cardiac cavity were very low, and no obvious interference extracardiac radioactivity was observed. The radioactive ratio of the left ventricular myocardium to cardiac blood pool and adjacent liver were high. Compared with 13N-NH3·H2O, there were no significant differences in functional parameters, including SRS, Extend, TPD and LVEF.
The results preliminaryly show that 18F-FIurpiridaz is a promising positron MPI agent with good image quality, ability of accurately evaluating cardiac function, and also convenience for application.

18F-Flurpiridaz is a promising investigational radiotracer for PET myocardial perfusion imaging with favorable properties for quantification of myocardial blood flow (MBF). We sought to validate the incremental diagnostic value of absolute MBF quantification in a large multicenter trial against quantitative coronary angiography.
We retrospectively analyzed a subset of patients (N = 231) from the first phase 3 flurpiridaz trial (NCT01347710). Dynamic PET data at rest and pharmacologic stress were fit to a previously validated 2-tissue-compartment model. Absolute MBF and myocardial flow reserve (MFR) were compared with coronary artery disease severity quantified by invasive coronary angiography on a per-patient and per-vessel basis.
Stress MBF per-vessel accurately identified obstructive disease (c-index 0.79) and progressively declined with increasing stenosis severity (2.35 ± 0.71 in patients without CAD; 1.92 ± 0.49 in non-obstructed territories of CAD patients; and 1.54 ± 0.50 in diseased territories, P < 0.05). MFR similarly declined with increasing stenosis severity (3.03 ± 0.94; 2.69 ± 0.95; and 2.33 ± 0.86, respectively, P < 0.05). In multivariable logistic regression modeling, stress MBF and MFR provided incremental diagnostic value beyond patient characteristics and relative perfusion analysis.
Clinical myocardial blood flow measurement with 18F-flurpiridaz cardiac PET shows promise for routine application.

The heart failure epidemic continues to rise with coronary artery disease as one of its main causes. Novel concepts for risk stratification to guide the referring cardiologist towards revascularization procedures are of significant value. Myocardial perfusion imaging using single-photon emission computed tomography (SPECT) agents has demonstrated high accuracy for the detection of clinically relevant stenoses. With positron emission tomography (PET) becoming more widely available, mainly due to its diagnostic performance in oncology, perfusion imaging with that modality is more practical than in the past and overcomes existing limitations of SPECT MPI. Advantages of PET include more reliable quantification of absolute myocardial blood flow, the routine use of computed tomography for attenuation correction, a higher spatiotemporal resolution and a higher count sensitivity. Current PET radiotracers such as rubidium-82 (half-life, 76 s), oxygen-15 water (2 min) or nitrogen-13 ammonia (10 min) are labeled with radionuclides with very short half-lives, necessitating that stress imaging is performed under pharmacological vasodilator stress instead of exercise testing. However, with the introduction of novel 18F-labeled MPI PET radiotracers (half-life, 110 min), the intrinsic advantages of PET can be combined with exercise testing. Additional advantages of those radiotracers include, but are not limited to: potentially improved cost-effectiveness due to the use of pre-existing delivery systems and superior imaging qualities, mainly due to the shortest positron range among available PET MPI probes. In the present review, widely used PET MPI radiotracers will be reviewed and potential novel 18F-labeled perfusion radiotracers will be discussed.