Highly Specific and Sensitive Radioiodinated Agent for In Vivo Imaging of Superoxide through Superoxide-Initiated Retention

Superoxide (O2•–) 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 O2•– in vivo. 125/131I-PISO was obtained in good radiochemical yield (65.4 ± 9.2%) and high radiochemical purity (>98%) after HPLC purification. 125/131I-PISO (log P = 2.46) could be oxidized by O2•– selectively and sensitively, converted to a hydrophilic compound 125/131I-PISA (log P = −1.62) with negative charge simultaneously and conglutinated with biomolecules by electrostatic interactions. The specific accumulation of 131I-PISA in the O2•– rich region were verified in cell efflux assay and SPECT/CT imaging in situ O2•– enrichment model mice. SPECT/CT imaging showed higher accumulation of 125I-PISO in the inflamed ankles compared to the control. Radioiodinated PISO is a potential SPECT agent to image O2•– distribution in vivo through specific and ...