Comparative evaluation of the algorithms for parametric mapping of the novel myocardial PET imaging agent 18 F-FPTP

Abstract

Objective

(¹⁸F-fluoropentyl)triphenylphosphonium salt (¹⁸F-FPTP) is a new promising myocardial PET imaging tracer. It shows high accumulation in cardiomyocytes and rapid clearance from liver. We performed compartmental analysis of ¹⁸F-FPTP PET images in rat and evaluated two linear analyses: linear least-squares (LLS) and a basis function method (BFM) for generating parametric images. The minimum dynamic scan duration for kinetic analysis was also investigated and computer simulation undertaken.

Methods

¹⁸F-FPTP dynamic PET (18 min) and CT images were acquired from rats with myocardial infarction (MI) (n = 12). Regions of interest (ROIs) were on the left ventricle, normal myocardium, and MI region. Two-compartment (K ₁ and k ₂; 2C2P) and three-compartment (K ₁–k ₃; 3C3P) models with irreversible uptake were compared for goodness-of-fit. Partial volume and spillover correction terms (V _a and α = 1 − V _a ) were also incorporated. LLS and BFM were applied to ROI- and voxel-based kinetic parameter estimations. Results were compared with the standard ROI-based nonlinear least-squares (NLS) results of the corresponding compartment model. A simulation explored statistical properties of the estimation methods.

Results

The 2C2P model was most suitable for describing ¹⁸F-FPTP kinetics. Average K ₁, k ₂, and V _a values were, respectively, 6.8 (ml/min/g), 1.1 (min⁻¹), and 0.44 in normal myocardium and 1.4 (ml/min/g), 1.1 (min⁻¹), and 0.32, in MI tissue. Ten minutes of data was sufficient for the estimation. LLS and BFM estimations correlated well with NLS values for the ROI level (K ₁: y = 1.06x + 0.13, r ²  = 0.96 and y = 1.13x + 0.08, r ²  = 0.97) and voxel level (K ₁: y = 1.22x − 0.30, r ²  = 0.90 and y = 1.26x + 0.00, r ²  = 0.92). Regional distribution of kinetic parametric images (αK ₁, K ₁, k ₂, V _a) was physiologically relevant. LLS and BFM showed more robust characteristics than NLS in the simulation.

Conclusions

Fast kinetics and highly specific uptake of ¹⁸F-FPTP by myocardium enabled quantitative analysis with the 2C2P model using only the initial 10 min of data. LLS and BFM were feasible for estimating voxel-wise parameters. These two methods will be useful for quantitative evaluation of ¹⁸F-FPTP distribution in myocardium and in further studies with different conditions, disease models, and species.

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