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Radioiodinated Pentixather for SPECT Imaging of Expression of the Chemokine Receptor CXCR4 in Rat Myocardial-Infarction-Reperfusion Models.

Analytical Chemistry 2018 August 8
The purpose of this study is to develop a specific CXCR4-targeting radioiodinated agent (125 I- or 131 I-pentixather) for single-photon-emission-computed-tomography (SPECT) imaging of CXCR4 expression in myocardial-infarction-reperfusion (MI/R) rat models. After SPECT-CT imaging with 125 I-pentixather at 4, 12, and 36 h and 3 and 7 days after MI/R, the models were validated by ex vivo autoradiography, TTC staining, and immunohistochemistry and in vivo echocardiography and classical 99m Tc-MIBI perfusion imaging. The SPECT-CT images showed that the infarcted myocardium (IM) could be visualized with high quality as early as 4 h and reached the maximum at 3 days after MI/R and that CXCR4 upregulation was still visible at 7 days after MI/R. In the biodistribution study, high uptakes in the IM (0.99 ± 0.13, 1.52 ± 0.29, 1.75 ± 0.22, 1.94 ± 0.27, and 0.61 ± 0.14% ID/g at 4, 12, and 36 h and 3 and 7 days after MI/R, respectively) were observed that were much higher than that of normal myocardium. The highest uptake was reached at 3 days after MI/R, which agreed well with the SPECT results. In addition, the radioactivity uptakes of the IM in both the biodistribution and SPECT imaging could be blocked effectively by excess amounts of AMD3465, indicating the high specificity of radioiodinated pentixather to CXCR4. On the basis of its promising properties, 125 I-pentixather may serve as a powerful CXCR4-expression diagnostic probe for evaluating lesions and monitoring therapy responses in patients with cardiovascular diseases.

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