Gadolinium chelate with DO3A conjugated 2-(diphenylphosphoryl)-ethyldiphenylphosphonium cation as potential tumor-selective MRI contrast agent

• Published in: Biomaterials Vol. 33; no. 36; pp. 9225 - 9231
• Main Authors: Chandrasekharan, Prashant, Yong, Cai-Xian, Poh, Zihan, He, Tao, He, Zhengjie, Liu, Shuang, Robins, Edward G, Chuang, Kai-Hsiang, Yang, Chang-Tong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.12.2012
• Subjects: Advanced Basic Science; Animals; Cell Line; Cell Line, Tumor; Contrast agent; Contrast Media - chemistry; Dentistry; DO3A conjugated cation; Gadolinium - chemistry; Gadolinium complex; HeLa Cells; Heterocyclic Compounds - chemistry; Humans; Magnetic resonance imaging (MRI); Magnetic Resonance Imaging - methods; Meglumine - chemistry; Mice; Organometallic Compounds - chemistry; Tumor targeting; Xenograft Model Antitumor Assays; Magnetic resonance imaging (MRI); DO3A conjugated cation; Tumor targeting; Gadolinium complex; Contrast agent
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2012.08.071

Abstract A series of organic cations, such as triphenylphosphonium (TPP), 2-(diphenylphosphoryl)-ethyldiphenylphosphonium (TPEP), represent molecular probes for imaging tumors. These organic cations have been labeled with64 Cu radioisotope for imaging tumors by positron emission tomograghy (PET). Among these organic cation ligands, TPEP was selected for extensive evaluation using magnetic resonance imaging (MRI) based on its higher tumor uptake and better Tumor/Background (T/B) ratios. This report presents the development of a new Gd(III) chelate [Gd(DO3A-xy-TPEP)]+ as a cationic MRI contrast agent. The contrast agent was synthesized and characterized in vitro and in vivo. In vitro cell viability showed low cytotoxicity at low [Gd] concentrations. Cell uptake experiment shows that the [Gd(DO3A-xy-TPEP)]+ has high affinity for tumor cells. The in vitro T1 relaxivity measured at 9.4 T is about 50% higher than those of contrast agents in clinical use: Gd-DTPA (Magnevist) and Gd-DOTA (Dotarem). In vivo imaging studies in tumor-bearing mice at 7.0 T demonstrated significant signal enhancement at the site of the tumors. [Gd(DO3A-xy-TPEP)]+ is a promising tumor-targeting MRI contrast agent for diagnostic imaging.