Bullok Kristin E, Gammon Seth T, Violini Stefania, Prantner Andrew M, Villalobos Victor M, Sharma Vijay, Piwnica-Worms David
Washington University Medical School, St Louis, MO 63110, USA.
Mol Imaging. 2006 Jan-Mar;5(1):1-15.
Rapid and efficient delivery of imaging probes to the cell interior using permeation peptides has enabled novel applications in molecular imaging. Membrane permeant peptides based on the HIV-1 Tat basic domain sequence, GRKKRRQRRR, labeled with fluorophores and fluorescent proteins for optical imaging or with appropriate peptide-based motifs or macrocycles to chelate metals, such as technetium for nuclear scintigraphy and gadolinium for magnetic resonance imaging, have been synthesized. In addition, iron oxide complexes have been functionalized with the Tat basic domain peptides for magnetic resonance imaging applications. Herein we review current applications of permeation peptides in molecular imaging and factors influencing permeation peptide internalization. These diagnostic agents show concentrative cell accumulation and rapid kinetics and display cytosolic and focal nuclear accumulation in human cells. Combining methods, dual-labeled permeation peptides incorporating fluorescein maleimide and chelated technetium have allowed for both qualitative and quantitative analysis of cellular uptake. Imaging studies in mice following intravenous administration of prototypic diagnostic permeation peptides show rapid whole-body distribution allowing for various molecular imaging applications. Strategies to develop permeation peptides into molecular imaging probes have included incorporation of targeting motifs such as molecular beacons or protease cleavable domains that enable selective retention, activatable fluorescence, or targeted transduction. These novel permeation peptide conjugates maintain rapid translocation across cell membranes into intracellular compartments and have the potential for targeted in vivo applications in molecular imaging and combination therapy.
利用渗透肽将成像探针快速高效地递送至细胞内部，已在分子成像领域实现了新的应用。基于HIV-1 Tat碱性结构域序列GRKKRRQRRR合成的膜渗透性肽，已被标记上荧光团和荧光蛋白用于光学成像，或标记上合适的基于肽的基序或大环以螯合金属，如用于核闪烁显像的锝和用于磁共振成像的钆。此外，已用Tat碱性结构域肽对氧化铁复合物进行功能化，用于磁共振成像应用。在此，我们综述了渗透肽在分子成像中的当前应用以及影响渗透肽内化的因素。这些诊断剂表现出细胞内的集中积累和快速动力学，并在人类细胞中显示出胞质和局灶性核积累。通过结合方法，将荧光素马来酰亚胺和螯合锝结合的双标记渗透肽实现了对细胞摄取的定性和定量分析。静脉注射原型诊断性渗透肽后在小鼠体内进行的成像研究显示，其在全身快速分布，可用于各种分子成像应用。将渗透肽开发成分子成像探针的策略包括引入靶向基序，如分子信标或蛋白酶可裂解结构域，以实现选择性保留、可激活荧光或靶向转导。这些新型渗透肽缀合物在细胞膜上保持快速转运至细胞内区室，并具有在分子成像和联合治疗中进行靶向体内应用的潜力。
