Division of Nanobionics, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, PR China; University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, PR China.
Division of Nanobionics, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, PR China; University of Science and Technology of China, 19 Ren'ai Road, Suzhou 215123, PR China.
Biomaterials. 2014 Apr;35(13):4168-74. doi: 10.1016/j.biomaterials.2014.01.073. Epub 2014 Feb 21.
Three Gd-DOTA-peptide complexes with different peptide sequence are synthesized and used as T1 contrast agent to label human mesenchymal stem cells (hMSCs) for magnetic resonance imaging study. The peptides include a universal cell penetrating peptide TAT, a linear MSC-specific peptide EM7, and a cyclic MSC-specific peptide CC9. A significant difference in labeling efficacy is observed between the Gd-DOTA-peptides as well as a control Dotarem. All Gd-DOTA-peptides as well as Dotarem induce significant increase in T1 relaxation rate which is in favor of T1-weighted MR imaging. Gd-DOTA-CC9 yields the maximum labeling efficacy but poor T1 contrast enhancement. Gd-DOTA-EM7 yields the minimum labeling efficacy but better T1 contrast enhancement. Gd-DOTA-TAT yields a similar labeling efficacy as Gd-DOTA-CC9 and similar T1 contrast enhancement as Gd-DOTA-EM7. The underlying mechanism that governs T1 contrast enhancement effect is discussed. Our results suggest that T1 contrast enhancement induced by Gd-DOTA-peptides depends not only on the introduced cellular Gd content, but more importantly on the effect that Gd-DOTA-peptides exert on the T1-relaxation and T2-relaxation processes/rates. Both T1 and particularly T2 relaxation rate have to be taken into account to interpret T1 contrast enhancement. In addition, the interpretation has to be based on cellular instead of aqueous longitudinal and transverse relaxivities of Gd-DOTA-peptides.
三种不同肽序列的 Gd-DOTA-肽复合物被合成并用作 T1 对比剂，用于磁共振成像研究标记人间充质干细胞（hMSCs）。这些肽包括通用细胞穿透肽 TAT、线性 MSC 特异性肽 EM7 和环状 MSC 特异性肽 CC9。在标记效率方面，Gd-DOTA-肽与对照 Dotarem 之间存在显著差异。所有 Gd-DOTA-肽和 Dotarem 均诱导 T1 弛豫率显著增加，有利于 T1 加权磁共振成像。Gd-DOTA-CC9 产生最大的标记效率，但 T1 对比增强效果差。Gd-DOTA-EM7 产生最小的标记效率，但 T1 对比增强效果更好。Gd-DOTA-TAT 的标记效率与 Gd-DOTA-CC9 相似，T1 对比增强与 Gd-DOTA-EM7 相似。讨论了控制 T1 对比增强效果的潜在机制。我们的结果表明，Gd-DOTA-肽诱导的 T1 对比增强不仅取决于引入的细胞内 Gd 含量，而且更重要的是取决于 Gd-DOTA-肽对 T1 弛豫和 T2 弛豫过程/速率的影响。为了解释 T1 对比增强，必须同时考虑 T1 和特别是 T2 弛豫率。此外，解释必须基于细胞而不是 Gd-DOTA-肽的水相纵向和横向弛豫率。
