Prantner Andrew M, Sharma Vijay, Garbow Joel R, Piwnica-Worms David
Washington University School of Medicine, St Louis, MO 63110, USA.
Mol Imaging. 2003 Oct;2(4):333-41. doi: 10.1162/15353500200303106.
Many MR contrast agents have been developed and proven effective for extracellular nontargeted applications, but exploitation of intracellular MR contrast agents has been elusive due to the permeability barrier of the plasma membrane. Peptide transduction domains can circumvent this permeability barrier and deliver cargo molecules to the cell interior. Based upon enhanced cellular uptake of permeation peptides with D-amino acid residues, an all-D Tat basic domain peptide was conjugated to DOTA and chelated to gadolinium. Gd-DOTA-D-Tat peptide in serum at room temperature showed a relaxivity of 7.94 +/- 0.11 mM(-1) sec(-1) at 4.7 T. The peptide complex displayed no significant binding to serum proteins, was efficiently internalized by human Jurkat leukemia cells resulting in intracellular T1 relaxation enhancement, and in preliminary T1-weighted MRI experiments, significantly enhanced liver, kidney, and mesenteric signals.
许多磁共振成像（MR）造影剂已被开发出来，并在细胞外非靶向应用中证明有效，但由于质膜的通透性屏障，细胞内MR造影剂的开发一直难以实现。肽转导域可以绕过这种通透性屏障，将货物分子递送至细胞内部。基于含D-氨基酸残基的渗透肽对细胞摄取的增强作用，将一种全D型Tat碱性结构域肽与DOTA偶联，并螯合钆。室温下血清中的钆-DOTA-D-Tat肽在4.7 T时的弛豫率为7.94±0.11 mM⁻¹ sec⁻¹。该肽复合物与血清蛋白无明显结合，能被人Jurkat白血病细胞有效内化，导致细胞内T1弛豫增强，并且在初步的T1加权MRI实验中，显著增强了肝脏、肾脏和肠系膜的信号。
