A short-scan method for k3 estimation with moderately reversible PET ligands: Application of irreversible model to early-phase PET data

Long dynamic scans (60-120 min) are often required for estimating the k3 value, an index of receptor density, by positron emission tomography (PET). However, the precision of k3 is usually low in kinetic analyses for reversible PET ligands compared with irreversible ligands. That is largely due to unstable estimation of the dissociation rate constant, k4. We propose a novel '3P+' method for estimating k3 of moderately reversible ligands, where a 3-parameter model without k4 is applied to early-phase PET data to obtain a good model-fit of k3 estimation. By using [11C] Pittsburgh compound B (PIB) (k4 = 0.018/min) as an example of a moderately reversible ligand, the 3P+ method simulation with a 28 min PET scan yielded less than 3% k3 relative bias with a +100% k3 change. In [11C]PIB PET scans of 15 normal controls (NC) and nine patients with Alzheimer's disease (AD), the 3P+ method provided a precise k3 estimate (mean SE of 13.6% in parietal cortex; covariance matrix method). The results revealed linear correlations (r = 0.964) of parietal k3 values in 24 subjects between 28 minute 3P+ method and conventional 90 minute 4-parameter method. A good separation of k3 between NC and AD groups (P < 0.001; t-test) was replicated in 28 minute 3P+ method. The short-scan 3P+ method may be a practical alternative method for analyzing reversible ligands.