Positron Emission Tomography Imaging Evaluation of a Novel ¹⁸F‑Labeled Sigma‑1 Receptor Radioligand in Cynomolgus Monkeys

We report a convenient radiosynthesis and the first positron emission tomography (PET) imaging evaluation of [¹⁸F]­FBFP as a potent sigma-1 (σ₁) receptor radioligand with advantageous characteristics. [¹⁸F]­FBFP was synthesized in one step from an iodonium ylide precursor. In cynomolgus monkeys, [¹⁸F]­FBFP displayed high brain uptake and suitable tissue kinetics for quantitative analysis. It exhibited heterogeneous distribution with higher regional volume of distribution (V_T) values in the amygdala, hippocampus, insula, and frontal cortex. Pretreatment with the σ₁ receptor agonist SA4503 (0.5 mg/kg) significantly reduced radioligand uptake in the monkey brain (>95%), indicating high binding specificity of [¹⁸F]­FBFP in vivo. Compared with (S)-[¹⁸F]­fluspidine, [¹⁸F]­FBFP possessed higher regional nondisplaceable binding potential (BP_ND) values across the brain regions. These findings demonstrate that [¹⁸F]­FBFP is a highly promising PET radioligand for imaging and quantification of σ₁ receptors in humans.