1. Center for Molecular Imaging and Translational Medicine, Xiamen University, Xiamen, Fujian, China, 361005.
Theranostics. 2012;2(8):746-56. doi: 10.7150/thno.4762. Epub 2012 Aug 6.
The aim of this study is to determine if dynamic optical imaging could provide comparable kinetic parameters to that of dynamic PET imaging by a near-infrared dye/(64)Cu dual-labeled cyclic RGD peptide.
The integrin α(v)β(3) binding RGD peptide was conjugated with a macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for copper labeling and PET imaging and a near-infrared dye ZW-1 for optical imaging. The in vitro biological activity of RGD-C(DOTA)-ZW-1 was characterized by cell staining and receptor binding assay. Sixty-min dynamic PET and optical imaging were acquired on a MDA-MB-435 tumor model. Singular value decomposition (SVD) method was applied to compute the dynamic optical signal from the two-dimensional optical projection images. Compartment models were used to quantitatively analyze and compare the dynamic optical and PET data.
The dual-labeled probe (64)Cu-RGD-C(DOTA)-ZW-1 showed integrin specific binding in vitro and in vivo. The binding potential (Bp) derived from dynamic optical imaging (1.762 ± 0.020) is comparable to that from dynamic PET (1.752 ± 0.026).
The signal un-mixing process using SVD improved the accuracy of kinetic modeling of 2D dynamic optical data. Our results demonstrate that 2D dynamic optical imaging with SVD analysis could achieve comparable quantitative results as dynamic PET imaging in preclinical xenograft models.
本研究旨在通过近红外染料/(64)Cu 双标记环 RGD 肽，确定动态光学成像是否能提供与动态 PET 成像相当的动力学参数。
将整合素 α(v)β(3)结合的 RGD 肽与大环螯合剂 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(DOTA)进行偶联，用于铜标记和 PET 成像，以及近红外染料 ZW-1 用于光学成像。RGD-C(DOTA)-ZW-1 的体外生物学活性通过细胞染色和受体结合测定进行表征。在 MDA-MB-435 肿瘤模型上进行 60 分钟的动态 PET 和光学成像。应用奇异值分解(SVD)方法从二维光学投影图像中计算动态光学信号。使用房室模型对动态光学和 PET 数据进行定量分析和比较。
双标记探针(64)Cu-RGD-C(DOTA)-ZW-1 在体外和体内均显示出整合素特异性结合。从动态光学成像得出的结合势(Bp)(1.762±0.020)与从动态 PET 成像得出的结果相当(1.752±0.026)。
使用 SVD 的信号解混过程提高了 2D 动态光学数据的动力学建模准确性。我们的结果表明，在临床前异种移植模型中，使用 SVD 分析的 2D 动态光学成像可以获得与动态 PET 成像相当的定量结果。
