PET imaging of apoptosis with 64Cu-labeled streptavidin following pretargeting of phosphatidylserine with biotinylated annexin-V
PET imaging of apoptosis with 64Cu-labeled streptavidin following pretargeting of phosphatidylserine with biotinylated annexin-V
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DOI：
10.1007/s00259-006-0199-y
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发表时间：
2007-02-01
影响因子：
9.1
通讯作者：
van Lier, Johan E.
中科院分区：
文献类型：
--
作者：
Cauchon, Nicole;Langlois, Rejean;van Lier, Johan E.
目的：细胞凋亡的体内检测是一种在心脏病学和肿瘤学中具有潜在临床应用的诊断工具。放射性标记的膜联蛋白-V（anxV）由于其对凋亡细胞表面的分子标志磷脂酰丝氨酸（PS）的强亲和力而成为体内凋亡检测的理想探针。大多数用于可视化细胞凋亡的临床研究都使用了Tc-99 m-anxV;然而，其较差的分布特征通常会影响图像质量。在这项研究中，治疗后的肿瘤细胞凋亡是可视化的正电子发射断层扫描（PET），使用铜-64-标记的链霉亲和素（SAV），凋亡细胞与生物素化anxV.方法：凋亡诱导的光动力疗法（PDT），使用酞菁染料作为光敏剂，在荷瘤小鼠，和红光。PDT后，给小鼠静脉注射生物素化anxV，2小时后进行抗生物素蛋白追踪，再过2小时后用Cu-64-DOTA-生物素-SAv。结果：PET图像描绘了早在Cu-64-DOTA-生物素-SAv给药后30分钟治疗的肿瘤中的凋亡，肿瘤与背景的比率在注射后3小时达到最大值，即，PDT后7 h。省略施用生物素化anxV或抗生物素蛋白追踪未能提供清晰的PET图像，证实所有三个步骤对于充分可视化细胞凋亡是必不可少的。此外，通过示踪剂摄取模式检测早期或延迟apoptosis.Conclusion的差异，明确认识到光敏剂，直接或通过初始血管淤滞靶向肿瘤细胞之间的作用机制的差异：本研究表明了一个三步Cu-64 pretargeting程序PET成像的凋亡的疗效。我们的数据还证实了小动物PET在评估癌症治疗方案方面的有用性。
Purpose: In vivo detection of apoptosis is a diagnostic tool with potential clinical applications in cardiology and oncology. Radiolabeled annexin-V (anxV) is an ideal probe for in vivo apoptosis detection owing to its strong affinity for phosphatidylserine ( PS), the molecular flag on the surface of apoptotic cells. Most clinical studies performed to visualize apoptosis have used Tc-99m-anxV; however, its poor distribution profile often compromises image quality. In this study, tumor apoptosis after therapy was visualized by positron emission tomography ( PET) using Cu-64-labeled streptavidin (SAv), following pretargeting of apoptotic cells with biotinylated anxV.Methods: Apoptosis was induced in tumor-bearing mice by photodynamic therapy (PDT) using phthalocyanine dyes as photosensitizers, and red light. After PDT, mice were injected i.v. with biotinylated anxV, followed 2 h later by an avidin chase, and after another 2 h with Cu-64-DOTA-biotin-SAv. PET images were subsequently recorded up to 13 h after PDT.Results: PET images delineated apoptosis in treated tumors as early as 30 min after Cu-64-DOTA-biotin-SAv administration, with tumor-to-background ratios reaching a maximum at 3 h post-injection, i.e., 7 h post-PDT. Omitting the administration of biotinylated anxV or the avidin chase failed to provide a clear PET image, confirming that all three steps are essential for adequate visualization of apoptosis. Furthermore, differences in action mechanisms between photosensitizers that target tumor cells directly or via initial vascular stasis were clearly recognized through differences in tracer uptake patterns detecting early or delayed apoptosis.Conclusion: This study demonstrates the efficacy of a three-step Cu-64 pretargeting procedure for PET imaging of apoptosis. Our data also confirm the usefulness of small animal PET to evaluate cancer treatment protocols.