Abnormal translocator protein 18 kDa (TSPO) expression in brain is markedly detected in activated microglia, choroid plexus, and reactive astrocytes . The selective TSPO-binding ligand can provide a powerful imaging tool to detect and monitor inflammatory brain disorders, because TSPO expression is significantly lower in the normal brains . Herein, we have designed an aromatic fluorine substituted imidazo[1,2-a]pyridine analogue, [18F]BS224 and presented its radio-synthesis and bioevaluation for PET imaging of neuroinflammation.
Aromatic [18F]fluorination of [18F]BS224 was conducted by two different precursors and conditions: i) diaryliodonium salts by using condition A; ii) pinacol boronate ester by using condition B . Finally, aromatic [18F]fluorination of [18F]BS224 was successfully optimized by nucleophilic substitution of the pinacol boronate ester precursor using [18F]fluoride with copper catalysts. The results, together with those obtained on in vitro TSPO binding, stability, in vivo PET imaging studies with specific and selective binding for TSPO, and a clear visibility of inflammatory lesion in animal models support the conclusion that [18F]BS224 is a promising TSPO PET imaging agent for neuroinflammation.
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