PET imaging of angiogenesis after myocardial infarction/reperfusion using a one-step labeled integrin-targeted tracer 18F-AlF-NOTA-PRGD2.
PET imaging of angiogenesis after myocardial infarction/reperfusion using a one-step labeled integrin-targeted tracer 18F-AlF-NOTA-PRGD2.
复制标题
使用一步标记的整合素靶向示踪剂 18F-AlF-NOTA-PRGD2 对心肌梗塞/再灌注后的血管生成进行 PET 成像。
DOI：
10.1007/s00259-011-2052-1
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发表时间：
2012-04
影响因子：
9.1
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Gao, Haokao;Lang, Lixin;Guo, Ning;Cao, Feng;Quan, Qimeng;Hu, Shuo;Kiesewetter, Dale O.;Niu, Gang;Chen, Xiaoyuan
αvβ3整合素是无创性血管生成成像的潜在靶点。本研究的目的是评价一种新的一步标记的整合素αvβ3靶向正电子发射计算机断层扫描探针，用于心肌梗死/再灌注(MI/R)动物模型的血管生成显像。雄性SD大鼠左冠状动脉短暂阻断45min后再灌流。经心电图、18F-FDG和心脏超声检查确诊为心肌梗死。用活体正电子发射计算机断层扫描技术测定再灌注后不同时间点心肌对18F-Alf-NOTA-PRGD2的摄取。用类似的程序标记对照多肽RAD，并用来确认其特异性。体外放射自显影分析和CD31/CD61双重免疫荧光染色以验证PET结果。18F-FDG和放射自显影证实了18F-Alf-NOTA-PRGD2的心肌来源。PET显像显示18F-Alf-NOTA-PRGD2在梗死区的局灶性蓄积在第3天开始增加(0.28±0.03%ID/g，p<；0.05)，在1周和3周达到高峰(分别为0.59±0.16和0.55±0.13%ID/g)。再灌流4个月后局灶积聚减少，但仍高于假手术组(0.31±0.01%ID/g，p<；0.05)。未标记的RGD多肽可显著降低示踪剂的摄取，表明该示踪剂的整合素特异性。在MI/R后1周，未与整合素结合的对照示踪剂18F-Alf-NOTA-RAD在梗死区的摄取仅为0.21±0.01%ID/g，放射自显影显示心肌梗死区摄取相同的趋势。CD3 1和CD6 1免疫组织化学染色显示，病灶示踪剂摄取的时间进程与血管密度和整合素β3的表达模式一致。使用一步标记的18F-Alf-NOTA-PRGD2的PET成像可以无创地纵向显示缺血-再灌注诱导的心肌血管生成。这种以整合素为靶点的PET示踪剂具有良好的体内动力学和易于制备的方法，有助于其未来用于闭塞心血管疾病患者的病变评估和治疗反应监测的临床翻译。
The αvβ3 integrin represents a potential target for noninvasive imaging of angiogenesis. The purpose of this study was to evaluate a novel one-step labeled integrin αvβ3 targeting PET probe, 18F-AlF-NOTA-PRGD2, for angiogenesis imaging in a myocardial infract/reperfusion (MI/R) animal model. Male SD rats underwent 45 min transient left coronary artery occlusion followed by reperfusion. The myocardial infarction was confirmed by ECG, 18F-FDG imaging and cardiac ultrasound. In vivo PET imaging were used to determine myocardial uptake of 18F-AlF-NOTA-PRGD2 at different time points following reperfusion. The control peptide RAD was labeled with a similar procedure and used to confirm the specificity. Ex vivo autoradiographic analysis and CD31/CD61 double immunofluoresence staining were performed to validate the PET results. Myocardial origin of the 18F-AlF-NOTA-PRGD2 accumulation was confirmed by 18F-FDG and autoradiography. PET imaging demonstrated increased focal accumulation of 18F-AlF-NOTA-PRGD2 in the infarcted area started at day 3 (0.28 ± 0.03 %ID/g, p < 0.05), peaked between 1 and 3 weeks (0.59 ± 0.16 and 0.55 ± 0.13 %ID/g, respectively). The focal accumulation decreased but still kept at a higher level than the sham group after 4 months of reperfusion (0.31 ± 0.01 %ID/g, p < 0.05). Pretreatment with unlabeled RGD peptide significantly decreased tracer uptake, indicating integrin specificity of this tracer. At 1 week after MI/R, uptake of the control tracer 18F-AlF-NOTA-RAD that does not bind to integrin, in the infarcted area, was only 0.21 ± 0.01 %ID/g. Autoradiographic imaging showed the same trend of uptake in myocardial infarction area. The time course of focal tracer uptake was consistent with the pattern of vascular density and integrin β3 expression as measured by CD31 and CD61 immunostaining analysis. PET imaging using one-step labeled 18F-AlF-NOTA-PRGD2 allows noninvasive visualization of ischemia-reperfusion induced myocardial angiogenesis longitudinally. The favorable in vivo kinetics and easy production method of this integrin targeted PET tracer facilitates its future clinical translation for lesion evaluation and therapy response monitoring in patients with occlusive cardiovascular diseases.
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影响因子：
15.9
作者：
Meoli, DF;Sadeghi, MM;Sinusas, AJ
通讯作者：
Sinusas, AJ
影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
4.7
作者：
Lang, Lixin;Li, Weihua;Guo, Ning;Ma, Ying;Zhu, Lei;Kiesewetter, Dale O.;Shen, Baozhong;Niu, Gang;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
影响因子：
14
作者：
Johnson, Lynne L.;Schofield, Lorraine;Haubner, Roland
通讯作者：
Haubner, Roland