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Background Myocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. F-18-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 F-18-flurpiridaz is feasible in mice. Methods Rest/stress PET-MPI was performed with F-18-flurpiridaz (0.6-3.0 MBq) in 27 mice aged 7-8 months. Regadenoson (0.1 mu g/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial F-18-flurpiridaz uptake was assessed for different time intervals by placing a volume of interest in the left ventricular myocardium. Results Tracer kinetics were best described by a two-tissue compartment model. K-1 ranged from 6.7 to 20.0 mL center dot cm(-3)center dot min(-1), while myocardial volumes of distribution (V-T) were between 34.6 and 83.6 mL center dot cm(-3). Of note, myocardial F-18-flurpiridaz uptake (%ID/g) was significantly correlated with K-1 at rest and following pharmacological vasodilation for all time intervals assessed. However, while Spearman's coefficients (r(s)) ranged between 0.478 and 0.681, R-2 values were generally low. In contrast, an excellent correlation of myocardial F-18-flurpiridaz uptake with V-T was obtained, particularly when employing the averaged myocardial uptake from 20 to 40 min post tracer injection (R-2 >= 0.98). Notably, K-1 and V-T were similarly sensitive to pharmacological vasodilation induction. Further, mean stress-to-rest ratios of K-1, V-T, and %ID/g F-18-flurpiridaz were virtually identical, suggesting that %ID/g F-18-flurpiridaz can be used to estimate coronary flow reserve (CFR) in mice. Conclusion Our findings suggest that a simplified assessment of relative myocardial perfusion and CFR, based on image-derived tracer uptake, is feasible with F-18-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents., Journal of Nuclear Cardiology, 30 (1), ISSN:1071-3581, ISSN:1532-6551

Non-invasive imaging of metabotropic glutamate receptor 5 (mGlu5) in the brain using PET is of interest in e.g., anxiety, depression, and Parkinson’s disease. Widespread application of the most widely used mGlu5 tracer, [11C]ABP688, is limited by the short physical half-life of carbon-11. [18F]PSS232 is a fluorinated analog with promising preclinical properties and high selectivity and specificity for mGlu5. In this first-in-man study, we evaluated the brain uptake pattern and kinetics of [18F]PSS232 in healthy volunteers. [18F]PSS232 PET was performed with ten healthy male volunteers aged 20–40 years. Seven of the subjects received a bolus injection and the remainder a bolus/infusion protocol. Cerebral blood flow was determined in seven subjects using [15O]water PET. Arterial blood activity was measured using an online blood counter. Tracer kinetics were evaluated by compartment modeling and parametric maps were generated for both tracers. At 90 min post-injection, 59.2 ± 11.1% of total radioactivity in plasma corresponded to intact tracer. The regional first pass extraction fraction of [18F]PSS232 ranged from 0.41 ± 0.06 to 0.55 ± 0.03 and brain distribution pattern matched that of [11C]ABP688. Uptake kinetics followed a simple two-tissue compartment model. The volume of distribution of total tracer (V T, ml/cm3) ranged from 1.18 ± 0.20 for white matter to 2.91 ± 0.51 for putamen. The respective mean distribution volume ratios (DVR) with cerebellum as the reference tissue were 0.88 ± 0.06 and 2.12 ± 0.10, respectively. The tissue/cerebellum ratios of a bolus/infusion protocol (30/70 dose ratio) were close to the DVR values. Brain uptake of [18F]PSS232 matched the distribution of mGlu5 and followed a two-tissue compartment model. The well-defined kinetics and the possibility to use reference tissue models, obviating the need for arterial blood sampling, make [18F]PSS232 a promising fluorine-18 labeled radioligand for measuring mGlu5 density in humans.

A shear stress-induced atherosclerosis mouse model was characterized for its expression of inflammation markers with focus on CD80. With this model, we evaluated two positron emission tomography (PET) radiotracers targeting CD80 as well as 2-deoxy-2-[18F]fluoro-d-mannose ([18F]FDM) in comparison with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG). A flow constrictive cuff implanted around the common carotid artery in apolipoprotein E knockout mice resulted in plaque formation. CD80 expression levels and plaque histopathology were evaluated. Serial PET/X-ray computed tomography scans were performed to follow inflammation. Plaque formation with increased levels of CD80 was observed. Histologically, plaques presented macrophage-rich and large necrotic areas covered by a thin fibrous cap. Of the CD80-specific tracers, one displayed an increased uptake in plaques by PET. Both [18F]FDG and [18F]FDM accumulated in atherosclerotic plaques. This mouse model presented, similar to humans, an increased expression of CD80 which renders it suitable for non-invasively targeting CD80-positive immune cells and evaluating CD80-specific radiotracers.

The formation of alkali and alkaline-earth metal picrate complexes with cyclo(Pro-Gly)n ionophores (1,n = 3; 2,n = 4) can facilitate the migration of metal ions across a bulk liquid CH2Cl2 membrane. The migration behavior was studied by measuring the solution absorption at 356 nm, using a UV/Vis spectrophotometer, and the rates can be determined by comparing the initial absorption of donor solutions with the absorption of the corresponding receiver solutions as the function of time. It was found that cyclic peptide 1 shows higher transport activity for the studied alkali and alkaline-earth metal ions than compound 2, which is related to the backbone flexibility of the cyclic peptides. The findings in this work suggest that the rate of ionophore-facilitated ion transport depends not only on the ability of complex formation in aqueous phase, but also on the ability of complex dissociation in organic phase.