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

The purpose of this study is to develop a specific CXCR4-targeting radioiodinated agent (125I/131I-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 125I-pentixather at 4, 12, 36 h, 3 and 7 d after MI/R, the models were validated by ex vivo autoradiography, TTC staining and immunohistochemistry, and in vivo echocardiography and classical 99mTc-MIBI perfusion imaging, respectively. 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 d after MI/R, and the CXCR4 upregulation is still visible at 7 d 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, 36 h, 3 and 7 d after MI/R respectively) were observed and which much higher than that of normal myocardium. The highest uptake was reached at 3 d after MI/R, which agreed well with the SPECT results. In addition, both the radioactivity uptakes of IM in the biodistribution and SPECT imaging could be blocked effectively by excess amount AMD3465, indicating the high specificity of radioiodinated pentixather to CXCR4. Based on the promising properties of 125I-pentixather, it may serve as a powerful CXCR4 expression diagnostic probe for evaluating lesion and monitoring therapy response in patients with cardiovascular diseases.