Fibrin-targeted PET probes for the detection of thrombi.
Fibrin-targeted PET probes for the detection of thrombi.
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DOI：
10.1021/mp300610s
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发表时间：
2013-03-04
影响因子：
4.9
通讯作者：
Caravan P
中科院分区：
文献类型：
--
作者：
Ciesienski KL;Yang Y;Ay I;Chonde DB;Loving GS;Rietz TA;Catana C;Caravan P
目前正在努力开发更好的方法，用于血栓的非侵入性检测和表征。在这里，我们描述了三个新的纤维蛋白靶向PET探针（FBP 1，FBP 2，FBP 3）的合成和评价。将三种纤维蛋白特异性肽在C-和N-末端缀合为DOTA-单酰胺，并用64 CuCl 2螯合。制备比活度范围为10 - 130 µCi/nmol的探针。尽管Cu-DOTA衍生化导致相对于母体肽的亲和力损失2-3倍，但肽和探针都表现出可溶性纤维蛋白片段DD（E）的纳摩尔解离常数（Kd）。在大鼠颈动脉血栓形成模型中进行生物分布和成像研究。对于FBP 1和FBP 2，在注射后120 min，含有血栓的血管显示出排泄器官（即肝脏和肾脏）之后的最高放射性浓度。这通过放射自显影法离体证实，其显示与对侧动脉相比，在含有血栓的动脉中> 4倍的活性。FBP 3显示出低得多的血栓摄取，并且该差异可追溯到该探针的更大代谢。使用FBP 1或FBP 2的混合MR-PET成像证实这些探针可有效检测该大鼠模型中的动脉血栓。血栓在PET图像上可见为高活性区域，对应于通过同步MR血管造影确定的动脉闭塞区域。FBP 1和FBP 2代表了血栓分子成像的有前途的新探针。
There is an ongoing effort to develop better methods for noninvasive detection and characterization of thrombus. Here we describe the synthesis and evaluation of three new fibrin-targeted PET probes (FBP1, FBP2, FBP3). Three fibrin-specific peptides were conjugated as DOTA-monoamides at the C- and N- termini, and chelated with 64CuCl2. Probes were prepared with a specific activity ranging from 10 – 130 µCi/nmol. Both the peptides and the probes exhibited nanomolar dissociation constants (Kd) for the soluble fibrin fragment DD(E), although the Cu-DOTA derivatization resulted in a 2–3 fold loss in affinity relative to the parent peptide. Biodistribution and imaging studies were performed in a rat model of carotid artery thrombosis. For FBP1 and FBP2 at 120 min post injection, the vessel containing thrombus showed the highest concentration of radioactivity after the excretory organs, i.e. the liver and kidneys. This was confirmed ex vivo by autoradiography which showed > 4-fold activity in the thrombus containing artery compared to the contralateral artery. FBP3 showed much lower thrombus uptake and the difference was traced to greater metabolism of this probe. Hybrid MR-PET imaging with FBP1 or FBP2 confirmed that these probes were effective for detection of arterial thrombus in this rat model. Thrombus was visible on PET images as a region of high activity that corresponded to a region of arterial occlusion identified by simultaneous MR angiography. FBP1 and FBP2 represent promising new probes for the molecular imaging of thrombus.
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影响因子：
4.7
作者：
Kolodziej, Andrew F.;Nair, Shrikumar A.;Graham, Philip;McMurry, Thomas J.;Ladner, Robert C.;Wescott, Charles;Sexton, Daniel J.;Caravan, Peter
通讯作者：
Caravan, Peter
影响因子：
158.5
作者：
AMARENCO, P;COHEN, A;BOUSSER, MG
通讯作者：
BOUSSER, MG
影响因子：
7.5
作者：
Douketis, James D.;Ginsberg, Jeffrey S.;Gerometta, Mike
通讯作者：
Gerometta, Mike
影响因子：
8.3
作者：
Mazighi, Mikael;Labreuche, Julien;Amarenco, Pierre
通讯作者：
Amarenco, Pierre
影响因子：
7.3
作者：
Boswell, CA;Sun, XK;Anderson, CJ
通讯作者：
Anderson, CJ