Characterization of [¹¹C]DASB and [¹⁸F]FE-PE2I using microPET imaging in SERT and DAT knockout rats

[¹¹C]DASB is widely used for PET imaging of brain serotonin transporters (SERT) and the tropane ligand [¹⁸F]FE-PE2I is used for PET imaging of dopamine transporters (DAT). However, their in vivo selectivity has not been confirmed using knockout (KO) models. This study aimed to provide direct in vivo evidence for the selectivity of these tracers using SERT and DAT KO rats.

High-resolution microPET imaging was performed in male SERT KO, DAT KO, and wild-type (WT) rats. Animals were dynamically scanned either for 60 min with [¹¹C]DASB for SERT, or for 45 min with [¹⁸F]FE-PE2I for DAT. Binding potential (BP_ND) was estimated using the simplified reference tissue model with the cerebellum as reference. Whole-brain regions were analyzed for [¹¹C]DASB, and striatal regions for [¹⁸F]FE-PE2I using descriptive and effect size metrics.

Specific tracer binding was visually absent in KO animals across all target regions. Quantitatively, [¹⁸F]FE-PE2I BPND in DAT KO rats was reduced by 94.2 % in the whole striatum, and [¹¹C]DASB BPND in SERT KO rats was reduced by a mean of 89.3 % across cortical, subcortical, and brainstem regions. These reductions were associated with larger effect sizes (Cohen's d ≥ 2.8).

This study provides in vivo characterization of [¹¹C]DASB and [¹⁸F]FE-PE2I selectivity and highlights the utility of genetic models for PET tracer evaluation.