Single-Photon Emission Computed Tomography Imaging Using Formyl Peptide Receptor 1 Ligand Can Diagnose Aortic Aneurysms in a Mouse Model.
Single-Photon Emission Computed Tomography Imaging Using Formyl Peptide Receptor 1 Ligand Can Diagnose Aortic Aneurysms in a Mouse Model.
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DOI：
10.1016/j.jss.2020.01.028
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
Sharma AK
中科院分区：
文献类型：
--
作者：
Shannon AH;Chordia MD;Spinosa MD;Su G;Ladd Z;Pan D;Upchurch GR Jr;Sharma AK
我们前期的研究表明，中性粒细胞的浸润和活化在腹主动脉瘤（AAA）的发病过程中起着重要的作用。然而，缺乏无创的、炎性细胞特异性的分子成像方法来提供AAA形成的早期诊断。甲酰基肽受体1 （FPR1）在炎症期间在中性粒细胞上迅速上调。因此，假设使用cFLFLF（一种聚乙二醇化的肽配体，与活化的中性粒细胞上的FPR1结合）可以通过单光子发射计算机断层扫描（SPECT）成像进行准确和无创的AAA诊断。雄性C57BL/6 （WT）小鼠外用弹性酶（0.4 U/ml 1型猪胰腺弹性酶）或热灭活弹性酶（对照）处理，用视频显微法测量主动脉直径。第14天进行比较组织学检查，评估主动脉组织中性粒细胞浸润情况。在弹性蛋白酶治疗后的第7天和第14天，我们使用c-FLFLF-Cy7探针进行了近红外荧光成像，并测量了切除主动脉组织的体外荧光强度。另一组动物在第14天使用SPECT/CT/PET三模扫描仪进行SPECT成像前2小时注射99mTc-c-FLFLF。第14天，用免疫染色法在主动脉组织中检测中性粒细胞与c-FLFLF的共表达。与对照组相比，弹性蛋白酶组在第7天和第14天的主动脉直径显著增加。同时，与对照组相比，经弹性酶治疗的主动脉组织中中性粒细胞浸润和弹性蛋白降解明显增加，平滑肌完整性下降。此外，与相应的对照组相比，在弹性酶处理的小鼠中，在第7天（大约增加2倍）和第14天（大约增加2.5倍），c-FLFLF-Cy7成像探针的荧光强度也显著增加。SPECT成像显示，与对照组相比，第14天AAA小鼠99mTc-cFLFLF放射性标记探针的信号强度增加了数倍。用c-FLFLF-Cy5对主动脉组织进行免疫染色显示，与对照组相比，AAA与中性粒细胞的共表达明显增加。cFLFLF是一种新型的FPR1配体，可以量化、无创地诊断AAAs的进展。这种炎症细胞特异性分子探针的临床应用，使用SPECT成像可以早期诊断AAA的形成，使有针对性的治疗干预和预防即将发生的主动脉破裂。
Our previous studies showed that neutrophil infiltration and activation plays an important role in the pathogenesis of abdominal aortic aneurysms (AAA). However, there is a lack of noninvasive, inflammatory cell-specific molecular imaging methods to provide early diagnosis of AAA formation. Formyl peptide receptor 1 (FPR1) is rapidly upregulated on neutrophils during inflammation. Therefore, it is hypothesized that use of cFLFLF, a PEGylated peptide ligand that binds FPR1 on activated neutrophils, would permit accurate and noninvasive diagnosis of AAA via single photon emission computed tomography (SPECT) imaging. Male C57BL/6 (WT) mice were treated with topical elastase (0.4 U/ml type 1 porcine pancreatic elastase) or heat inactivated elastase (control) and aortic diameter was measured by video micrometry. Comparative histology was performed on day 14 to assess neutrophil infiltration in aortic tissue. We performed near-infrared fluorescence imaging using c-FLFLF-Cy7 probe on days 7 and 14 post-elastase treatment and measured fluorescence intensity ex vivo in excised aortic tissue. Separate group of animals were injected with 99mTc-c-FLFLF two hours prior to SPECT imaging on day 14 using a SPECT/CT/PET trimodal scanner. Co-expression of neutrophils with c-FLFLF was also performed on aortic tissue by immunostaining on day 14. Aortic diameter was significantly increased in the elastase group compared to controls on days 7 and 14. Simultaneously, a marked increase in neutrophil infiltration and elastin degradation, as well as decrease in smooth muscle integrity, was observed in aortic tissue after elastase-treatment compared to controls. Moreover, a significant increase in fluorescence intensity of c-FLFLF-Cy7 imaging probe was also observed in elastase-treated mice on day 7 (approximately 2-fold increase) and day 14 (approximately 2.5-fold increase) compared to respective controls. SPECT imaging demonstrated a multi-fold increase in signal intensity for 99mTc-cFLFLF radiolabel probe in mice with AAA compared to controls on day 14. Immunostaining of aortic tissue with c-FLFLF-Cy5 demonstrated a marked increase in co-expression with neutrophils in AAA compared to controls. cFLFLF, a novel FPR1 ligand, enables quantifiable, noninvasive diagnosis and progression of AAAs. Clinical application of this inflammatory cell-specific, molecular probe using SPECT imaging may permit early diagnosis of AAA formation, enabling targeted therapeutic interventions and preventing impending aortic rupture.
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影响因子：
--
作者：
Ramaswamy AK;Hamilton M 2nd;Joshi RV;Kline BP;Li R;Wang P;Goergen CJ
通讯作者：
Goergen CJ
影响因子：
9.3
作者：
Madsen, Mark T.
通讯作者：
Madsen, Mark T.
DOI：
10.1161/01.atv.0000194098.82677.57
发表时间：
2006-01-01
影响因子：
8.7
作者：
Hyafil, F;Laissy, JP;Feldman, LJ
通讯作者：
Feldman, LJ
一种新型的中性粒细胞特异性宠物成像剂：CFLFLFK-PEG-64CU。
DOI：
10.2967/jnumed.108.056127
发表时间：
2009-05
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Locke LW;Chordia MD;Zhang Y;Kundu B;Kennedy D;Landseadel J;Xiao L;Fairchild KD;Berr SS;Linden J;Pan D
通讯作者：
Pan D
影响因子：
9.3
作者：
Courtois, Audrey;Nusgens, Betty V.;Sakalihasan, Natzi
通讯作者：
Sakalihasan, Natzi