Feasibility study of PET dynamic imaging of [18F]DHMT for quantification of reactive oxygen species in the myocardium of large animals

Abstract

Objectives: We aimed to develop a dynamic imaging technique for a novel PET superoxide tracer, [¹⁸F]DHMT, to allow for absolute quantification of myocardial reactive oxygen species (ROS) production in a large animal model.

Methods: Six beagle dogs underwent a single baseline dynamic [¹⁸F]DHMT PET study, whereas one animal underwent three serial dynamic studies over the course of chronic doxorubicin administration (1 mg·kg^-1·week^-1 for 15 weeks). During the scans, sequential arterial blood samples were obtained for plasma metabolite correction. The optimal compartment model and graphical analysis method were identified for kinetic modeling. Values for the left ventricular (LV) net influx rate, K_i, were reported for all the studies and compared with the LV standard uptake values (SUVs) and the LV-to-blood pool SUV ratios from the 60 to 90 minute static images. Parametric images were also generated.

Results: [¹⁸F]DHMT followed irreversible kinetics once oxidized within the myocardium in the presence of superoxide, as evidenced by the fitting generated by the irreversible two-tissue (2Ti) compartment model and the linearity of Patlak analysis. Myocardial K_i values showed a weak correlation with LV SUV (R² = 0.27), but a strong correlation with LV-to-blood pool SUV ratio (R² = 0.92). Generation of high-quality parametric images showed superior myocardial to blood contrast compared to static images.

Conclusions: A dynamic PET imaging technique for [¹⁸F]DHMT was developed with full and simplified kinetic modeling for absolute quantification of myocardial superoxide production in a large animal model.

Keywords: Reactive oxygen species (ROS); kinetic modeling; positron emission tomography (PET).