Efficient Construction of PET/Fluorescence Probe Based on Sarcophagine Cage: An Opportunity to Integrate Diagnosis with Treatment
Efficient Construction of PET/Fluorescence Probe Based on Sarcophagine Cage: An Opportunity to Integrate Diagnosis with Treatment
复制标题
基于石棺笼的PET/荧光探针的高效构建：诊断与治疗一体化的机会
DOI：
10.1007/s11307-012-0557-z
复制
发表时间：
2012-12-01
影响因子：
3.1
通讯作者：
Conti, Peter S.
中科院分区：
文献类型：
--
作者：
Liu, Shuanglong;Li, Dan;Conti, Peter S.
目的针对目前多模态探针构建平台和方法的不足，本研究从石斛笼中合成了一种异功能螯合剂BaAn（Boc）Sar，作为双模态探针构建的通用平台，并以此为基础合成了一种用于正电子发射断层扫描（PET）和荧光成像的双模态探针。c（RGDyK）2肽（表示为RGD 2）和荧光染料Cy5.5与BaAn（Boc）Sar缀合以形成BaAnSar-RGD 2-Cy5.5。然后在乙酸铵缓冲液中用64 Cu标记BaAnSar-RGD 2-Cy5.5。结果64 Cu标记的BaAnSar-RGD 2-Cy5.5在0.1 M NH 4 OAc缓冲液中于37 °C下10 min内标记成功，标记率为86.7 ± 4.4%（n= 3）。考虑到PET和光学成像的需要，64 Cu-BaBaSar-RGD 2的比活度控制在50-200 mCi/μmol。MicroPET定量分析显示，注射后1、4和20 h，U87 MG肿瘤摄取分别为6.41 ± 0.28、6.51 ± 1.45和5.92 ± 1.57% ID/g。通过放射性和荧光强度测量的肿瘤与肌肉比率之间获得了良好的相关性。作为一个概念的证明，动物手术研究表明，这种双模态探针将大大有利于患者，因为PET部分可用于肿瘤检测，和荧光部分将允许图像引导surgery.ConclusionsOur研究结果证明了制备双模态成像探针的有效性和可行性的基础上的石杉碱支架。由此产生的PET和荧光成像探针也具有巨大的临床转化潜力。
PurposeDue to the shortage of established platforms/methods for multimodality probe construction, in this study, we developed a heterofunctional chelator, BaAn(Boc)Sar, from sarcophagine cage as a general platform for dual-modality probe construction.ProceduresA dual-modality probe for positron-emission tomography (PET) and fluorescence imaging was synthesized using the developed BaAn(Boc)Sar chelator. The c(RGDyK)2peptide (denoted as RGD2) and fluorescence dye Cy5.5 were conjugated with BaAn(Boc)Sar to form BaAnSar-RGD2-Cy5.5. Then, BaAnSar-RGD2-Cy5.5 was labeled with64Cu in ammonium acetate buffer. PET and fluorescent imaging were carried out to evaluate64Cu-BaAnSar-RGD2-Cy5.5 in nude mice bearing U87MG glioblastoma xenograft.ResultsThe BaAnSar-RGD2-Cy5.5 was labeled with64Cu very efficiently in 0.1 M NH4OAc buffer within 10 min at 37 °C in the yield of 86.7 ± 4.4 % (n= 3). The specific activity of64Cu-BaBaSar-RGD2was controlled at 50–200 mCi/μmol for the consideration of both PET and optical imaging. MicroPET quantification analysis shows that the U87MG tumor uptake is 6.41 ± 0.28, 6.51 ± 1.45, and 5.92 ± 1.57 %ID/g at 1, 4, and 20 h postinjection, respectively. Good correlation was obtained between the tumor to muscle ratios measured by the radioactivity and fluorescence intensity. As a proof of concept, an animal surgery study demonstrated that this dual-modality probe would greatly benefit the patients because the PET moiety could be used for tumor detection, and the fluorescent moiety would allow image-guided surgery.ConclusionsOur findings demonstrated the effectiveness and feasibility of preparing dual-modality imaging probes based on the sarcophagine scaffold. The resulting PET and fluorescent imaging probe also holds a great potential for clinical translation.