Quantification of myocardial perfusion using BMS-747158-02
BMS-747158-02 ([18F]BMS-747158-01, [18F]flurpiridaz, 2-tert-Butyl-4-chloro-5-[4-(2-[18F]fluoroethoxymethyl)-benzyloxy]-2H-pyridazin-3-one, [18F]BMS) is a PET perfusion imaging agent which binds to the mitochondrial complex 1 (MC1) of the electron transport chain with high affinity. The tracer has high first-pass extraction and high retention in heart and kidney, and because of the high density of mitochondria in the myocardial muscle the image contrast is very good (see the references below).
The model input can be estimated from a ROI placed on LV. Metabolite correction is not needed (Nekolla et al., 2009).
Regional tissue curves (0-20 min after tracer injection) can be fitted using 3-compartmental model (two tissue compartments) with assumption of irreversible trapping (k4=0), using geometrical recovery and spill-over correction (Nekolla et al., 2009). K1 is assumed to represent blood flow. Nekolla et al. (2009) noticed a modest underestimation of myocardial blood flow (MBF), and discussed possible reasons for that.
Fractional uptake rates (FURs, retention) correlated well with MBF calculated using compartmental model, (Sherif et al., 2010), although FUR estimates will need a conversion factor to achieve quantitative MBF.
Feasible FUR analysis suggests that also Patlak plot (MTGA for trapped tracers), if linear, could be used to analyze the data. Patlak analysis provides net influx value (Ki), which is usually close to FUR estimate, and relates to compartment model parameters as Ki = K1 * k3/(k2+k3). If k2<<k3, then Ki≅K1 (which is assumed to represent MBF with this tracer). If k2>>k3, then Ki≅(K1/k2)*k3, which would probably not correlate with MBF. The k2 and k3 estimates reported by Nekolla et al. (2009; Table 4) would suggest that the former could be the case, but the level of FUR values (Sherif et al., 2010) would suggest something in between.
Standardized uptake values (SUVs) calculated 5-10 min after injection correlated well with MBF calculated using compartmental model, which would allow injecting tracer outside the PET scanner and performing a physical stress test (Sherif et al., 2010). Dual-gated imaging (Le Meunier et al., 2010) would probably further enhance the SUV estimates.
In rest-stress studies, the radioactivity that is remaining from the first study must be subtracted from the next image data. PET scanning in the second study can be started shortly before tracer injection, and the concentrations in the first frame are then subtracted from every frame (Nekolla et al., 2009). Lazewatsky et al. (2010) have developed a method for optimizing dose ratio and required inter-injection interval. Case et al. (2010) developed a method for automatic registration of rest and test perfusion images.
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