TY - JOUR T1 - Pretargeted SPECT/CT imaging of CD11b expression allows for detecting instable aorta aneurysm that full of inflammation JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 132 LP - 132 VL - 62 IS - supplement 1 AU - Guobing Liu AU - Xiaonan Zhou AU - Yingying Zhang AU - Yang Ming AU - Kai Zhu AU - Dengfeng Cheng Y1 - 2021/05/01 UR - http://jnm.snmjournals.org/content/62/supplement_1/132.abstract N2 - 132Purpose: Active inflammation is a risk factor predicting dissection or rupture of aortic aneurysm (AA). However, there is scarce method that can effectively assess inflammation in aortic wall of AA. The pre-targeted imaging strategy has advantages including excellent imaging contrast, low radiation exposure to normal organs, and suitability for short half-live radionuclide. The promising pre-targeted method is based on the biorthogonal click chemistry of inverse electron demand [4 + 2] Diels-Alder (IEDDA) cycloaddition between 1,2,4,5-terazine (Tz) and Trans-cyslooctene (TCO) alkene dienophile. The IEDDA has quick reaction rate with high efficiency but do not need catalyzer. In recent years, the IEDDA system showed its potential in the applications of in vivo tumor imaging, but has not been used in aortic imaging. The aim of this study was to investigate a novel pre-targeted single photon emission computed tomography (SPECT) imaging strategy (ant-CD11b-TCO/Tz-HYNIC-99mTc) for evaluating CD11b expression that was highly linked to inflammation in AA through the IEDDA system. Methods: A pre-targeted molecular detector, anti-CD11b-TCO, was synthesized and used for targeting inflammatory microenvironment of AA, and 99mTc-HYNIC-Tz, was created as imaging regent for SPECT/CT imaging. By using Raw-264.7 cell lines as positive cells and human umbilical vein endothelial cell (HUVEC) lines as negative counterparts, cell binging and relevant blocking test were performed to investigate affinity and specificity of the probe binding to inflammatory cells. C57BL/6J mice was fed with β-aminopropionitrile monofumarate (BAPN, 1g/kg/day) for 4 weeks to establish AA model. Then, anti-CD11b-TCO/Tz-HYNIC-99mTc pre-targeted SPECT/CT imaging were done to detect in-vivo inflammation in AA. Finally, ex vivo aortic breast specific gamma imaging (BSGI), and immunohistochemical staining were performed to confirm findings of in vivo SPECT/CT imaging. Results: The hybrid anti-CD11b-TCO presented with high TCO coupling ratio; and the 99mTc-HYNIC-Tz showed high radio-purity (> 95%), good in-vitro stability and a pharmacokinetics characteristic of quick clearance rate. Besides, anti-CD11b-TCO and 99mTc-HYNIC-Tz presented high conversion rate (~ 89%). The in-vitro clicked compound, 99mTc-HYNIC-Tz/TCO-anti-CD11b, showed high affinity and combining specificity with RAW-264.7 cells. The 99mTc-HYNIC-Tz/TCO-anti-CD11b pre-targeting SPECT/CT allows clear imaging inflammatory AA with high signal-to-normal ratio, which was significantly higher than those from AA mice that injected with 99mTc-HYNIC-Tz/TCO-IgG and C57BL/6J mice injected with 99mTc-HYNIC-Tz/TCO-anti-CD11b. This result was confirmed by in-vitro breast specific gamma imaging (BSGI) of corresponding aorta arteries right after SPECT/CT imaging and immunohistochemical staining of CD11b. Conclusions: SPECT/CT imaging using the pre-targeted strategy between anti-CD11b-TCO and 99mTc-HYNIC-Tz allows for detection of inflammation in the progressive AA. ER -