Imaging of atherosclerosis with [⁶⁴Cu]Cu-DOTA-TATE in a translational head-to-head comparison study with [¹⁸F]FDG, and Na[¹⁸F]F in rabbits

Atherosclerosis is a chronic inflammatory disease of the larger arteries that may lead to cardiovascular events. Identification of patients at highest risk of cardiovascular events is challenging, but molecular imaging using positron emission tomography (PET) may prove useful. The aim of this study was to evaluate and compare head-to-head three different PET tracers. Furthermore, tracer uptake is compared to gene expression alterations of the arterial vessel wall. Male New Zealand White rabbits (control group; n = 10, atherosclerotic group; n = 11) were used for the study. Vessel wall uptake was assessed with the three different PET tracers: [¹⁸F]FDG (inflammation), Na[¹⁸F]F (microcalcification), and [⁶⁴Cu]Cu-DOTA-TATE (macrophages), using PET/computed tomography (CT). Tracer uptake was measured as standardized uptake value (SUV), and arteries from both groups were analyzed ex vivo by autoradiography, qPCR, histology, and immunohistochemistry. In rabbits, the atherosclerotic group showed significantly higher uptake of all three tracers compared to the control group [¹⁸F]FDG: SUV_mean 1.50 ± 0.11 versus 1.23 ± 0.09, p = 0.025; Na[¹⁸F]F: SUV_mean 1.54 ± 0.06 versus 1.18 ± 0.10, p = 0.006; and [⁶⁴Cu]Cu-DOTA-TATE: SUV_mean 2.30 ± 0.27 versus 1.65 ± 0.16; p = 0.047. Of the 102 genes analyzed, 52 were differentially expressed in the atherosclerotic group compared to the control group and several genes correlated with tracer uptake. In conclusion, we demonstrated the diagnostic value of [⁶⁴Cu]Cu-DOTA-TATE and Na[¹⁸F]F for identifying atherosclerosis in rabbits. The two PET tracers provided information distinct from that obtained with [¹⁸F]FDG. None of the three tracers correlated significantly to each other, but [⁶⁴Cu]Cu-DOTA-TATE and Na[¹⁸F]F uptake both correlated with markers of inflammation. [⁶⁴Cu]Cu-DOTA-TATE was higher in atherosclerotic rabbits compared to [¹⁸F]FDG and Na[¹⁸F]F.