18F-labelled annexin V:: a PET tracer for apoptosis imaging

18F-labelled annexin V:: a PET tracer for apoptosis imaging
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DOI:
10.1007/s00259-003-1378-8
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发表时间:
2004-04-01
影响因子:
9.1
通讯作者:
Nishimura, S
Nishimura, S
中科院分区:
医学1区
文献类型:
--
作者:
Murakami, Y;Takamatsu, H;Nishimura, S

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膜联蛋白 V 可用于体外和体内检测凋亡细胞,因为它能够识别细胞凋亡过程中产生的细胞外磷脂酰丝氨酸。在本研究中,我们检查了氟 18 标记的膜联蛋白 V 作为正电子发射断层扫描示踪剂用于细胞凋亡成像的合成。比较了 [F-18]annexin V 和 technetium-99m 标记的annexin V(一种用于细胞凋亡成像的良好表征的 SPET 示踪剂)的分布。使用 N-琥珀酰亚胺基 4-[F-18]氟苯甲酸酯作为 F-18 标记试剂合成 [F-18]annexin V。合成并纯化的[F-18]膜联蛋白V通过SDS-PAGE确认。在离体成像实验中,在诱导心肌缺血24小时后将[F-18]膜联蛋白V静脉注射到大鼠体内,并检查其在左心室中的积累。 [F-18]annexin V 在左心室梗塞区域积聚,观察到凋亡细胞。在单独的实验中,将[F-18]annexin V或[Tc-99m]annexin V静脉注射到缺血或正常动物中,并比较示踪剂的分布。在缺血动物中,梗塞区域中[F-18]膜联蛋白V和[Tc-99m]膜联蛋白V的积累比非梗塞区域高约三倍。此外,示踪剂之间正常心脏中的积累与血液放射性的比率没有显着差异。然而,在正常动物中,肝脏、脾脏和肾脏中 [F-18]annexin V 的摄取远低于 [Tc-99m]annexin V。这些器官中 [F-18]annexin V 的低摄取可能代表了优于 [Tc-99m]annexin V 的优势。
Annexin V can be used to detect apoptotic cells in vitro and in vivo, based on its ability to identify extracellular phosphatidylserine, which arises during apoptosis. In the present study, we examined the synthesis of fluorine-18 labelled annexin V as a positron emission tomography tracer for apoptosis imaging. The distribution of [F-18]annexin V and technetium-99m labelled annexin V, a well-characterised SPET tracer for apoptosis imaging, was compared. [F-18]annexin V was synthesised using N-succinimidyl 4-[F-18]fluorobenzoate as an F-18 labelling reagent. Synthesised and purified [F-18]annexin V was confirmed by SDS-PAGE. In an ex vivo imaging experiment, [F-18]annexin V was intravenously injected into rats 24 h after the induction of myocardial ischaemia, and accumulation in the left ventricle was examined. [F-18]annexin V accumulated in the infarct area of the left ventricle, where apoptotic cells were observed. In separate experiments, [F-18]annexin V or [Tc-99m]annexin V was intravenously injected into ischaemic or normal animals, and the distribution of the tracers was compared. In ischaemic animals, accumulation of [F-18]annexin V and [Tc-99m]annexin V in the infarct area was about threefold higher than in the non-infarct area. Furthermore, the ratio of accumulation in the normal heart to the blood radioactivity was not significantly different between the tracers. In normal animals, however, the uptake of [F-18]annexin V in the liver, spleen and kidney was much lower than that of [Tc-99m]annexin V. The low uptake of [F-18]annexin V in these organs might represent an advantage over [Tc-99m]annexin V.