Highly Specific and Sensitive Radioiodinated Agent for in Vivo Imaging of Superoxide Through Superoxide-Initiated Retention

Superoxide (O-2(center dot-)) 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-2(center dot-) in vivo. I-125(/1)31-PISO was obtained in good radiochemical yield (65.4 +/- 9.2%) and high radiochemical purity (>98%) after HPLC purification. I-125/131-PISO (log P = 2.46) could be oxidized by 02.- selectively and sensitively, converted to a hydrophilic compound I-125/131-PISA (log P = -1.62) with negative charge simultaneously and conglutinated with biomolecules by electrostatic interactions. The specific accumulation of I-131-PISA in the O-2(center dot-) rich region were verified in cell efflux assay and SPECT/CT imaging in situ enrichment model mice. SPECT/CT imaging showed higher accumulation of I-12(5)-PISO in the inflamed ankles compared to the control. Radioiodinated PISO is a potential SPECT agent to image O-2(center dot-) distribution in vivo through specific and sensitive O-2(center dot-) triggered retention.