State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen 361102 , Fujian , China.
Zhongshan Hospital Affiliated to Xiamen University , Xiamen 361004 , Fujian , China.
Anal Chem. 2018 Nov 6;90(21):12971-12978. doi: 10.1021/acs.analchem.8b03642. Epub 2018 Oct 19.
Superoxide (O) is a specific molecular target for xenobiotics, cytokines, and bacteria during inflammatory diseases. The aim of this study is to develop a single-photon emission computed tomography (SPECT) imaging agent and to quantify the distribution of O in vivo. I-PISO was obtained in good radiochemical yield (65.4 ± 9.2%) and high radiochemical purity (>98%) after HPLC purification. I-PISO (log P = 2.46) could be oxidized by O selectively and sensitively, converted to a hydrophilic compound I-PISA (log P = -1.62) with negative charge simultaneously and conglutinated with biomolecules by electrostatic interactions. The specific accumulation of I-PISA in the O rich region were verified in cell efflux assay and SPECT/CT imaging in situ O enrichment model mice. SPECT/CT imaging showed higher accumulation of I-PISO in the inflamed ankles compared to the control. Radioiodinated PISO is a potential SPECT agent to image O distribution in vivo through specific and sensitive O triggered retention.
超氧化物 (O) 是炎症疾病中外源物质、细胞因子和细菌的特定分子靶标。本研究旨在开发单光子发射计算机断层扫描 (SPECT) 成像剂，并定量研究 O 在体内的分布。I-PISO 通过 HPLC 纯化后，可获得良好的放射化学产率 (65.4±9.2%) 和高放射化学纯度 (>98%)。I-PISO (log P = 2.46) 可被 O 选择性和灵敏地氧化，同时转化为带负电荷的亲水性化合物 I-PISA (log P = -1.62)，并通过静电相互作用与生物分子结合。细胞外排试验和原位 O 富集模型小鼠的 SPECT/CT 成像证实了 I-PISA 在 O 丰富区域的特异性积累。SPECT/CT 成像显示，与对照组相比，I-PISO 在炎症踝关节中的积累更高。放射性碘标记的 PISO 是一种有潜力的 SPECT 剂，可通过特异性和灵敏性的 O 触发保留来体内成像 O 分布。
