Development and Preliminary Evaluation of a I-Labeled Radioligand ([I]iodotrazoline) for In Vitro Detection of Imidazoline-2 Binding Site in the Brain.

Astrocytes exert multiple functions within the brain, including regulating neuroinflammation and maintaining homeostasis, and the reactive astrocytes are implicated in many neurodegenerative disorders. Imidazoline-2 binding site (IBS) has been established as a reliable biomarker for precisely quantifying reactive astrocytes. Here, we reported the development of [I]iodotrazoline ([I]), a novel IBS radioligand with high affinity ( = 6.8 nM) and exceptional selectivity over α-adrenoceptors (>1400 folds). autoradiography (ARG) using rat brain sections revealed a heterogeneous distribution of [I], with high signals in the medulla, midbrain, pons, and hypothalamus. Pretreatment with unlabeled IBS-selective ligands, BU224 and FTIMD, reduced the binding by >30%, indicating high specificity for IBS. ARG results confirmed this distribution pattern in the rat brain. Biodistribution results in mice demonstrated a rapid brain uptake of [I] (3.35% ID/g at 2 min postinjection) with slow washout. Metabolite analysis exhibited the desirable biostability of [I] in the rat brain. Altogether, this work provides a new I-labeled radioligand featuring a novel 2-trans-styryl-imidazoline scaffold, which shows significant specificity binding for IBS , serving as a valuable tool for IBS detection and astrocyte-related pathology research.