Characterization of a novel PET radioligand for mitochondrial complex I in nonhuman primate

The role of mitochondrial complex I (MC-I) dysfunction is well-documented across a range of neurodegenerative disorders. Recently, a novel positron emission tomography (PET) radioligand, [¹⁸F]CNL02, has been synthesized to target MC-I. In this paper, we provide a comprehensive characterization of [¹⁸F]CNL02, using nonhuman primate as a model system. In the brain of a rhesus macaque, [¹⁸F]CNL02 demonstrated specific binding in regions expressing MC-I. All observed brain regions showed rapid kinetic profiles. Analysis of arterial plasma indicated a swift clearance of [¹⁸F]CNL02 from the bloodstream. Metabolite analysis identified two predominant radiometabolites in the plasma. The regional brain time-activity curves (TACs) for [¹⁸F]CNL02 were effectively characterized through a two-tissue compartment model (2TCM). Furthermore, the total distribution volume was reliably estimated employing the Logan plot method. Consequently, continued development and refinement of [¹⁸F]CNL02 are imperative.