PEGylation of protein-based MRI contrast agents improves relaxivities and biocompatibilities.

Magnetic resonance imaging (MRI) has emerged as a leading diagnostic technique in clinical and preclinical settings. However, the application of MRI to assess specific disease markers for diagnosis and monitoring drug effect has been severely hampered by the lack of desired contrast agents with high relaxivities, and optimized in vivo retention time. We have reported the development of protein-based MRI contrast agents (ProCA1) by rational design of Gd(3+) binding sites into a stable protein resulting in significantly increased longitudinal (r(1)) and transverse (r(2)) relaxivities compared to Gd-DTPA. Here, we report a further improvement of protein contrast agents ProCA1 for in vivo imaging by protein modification with various sizes of polyethylene glycol (PEG) chain. PEGylation results in significant increases of both r(1) and r(2) relaxivities (up to 200%), and these high relaxivities persist even at field strengths up to 9.4 T. In addition, our experimental results demonstrate that modified contrast agents have significant improvement of in vivo MR imaging and biocompatibilities including dose efficiency, protein solubility, blood retention time and decreased immunogenicity. Such improvement can be important to the animal imaging and pre-clinical research at high or ultra-high field where there is an urgent need for molecular imaging probes and optimized contrast agent. Published by Elsevier Inc.

Citation

Shunyi Li, Jie Jiang, Jin Zou, Jingjuan Qiao, Shenghui Xue, Lixia Wei, Robert Long, Liya Wang, Adriana Castiblanco, Natalie White, Jen Ngo, Hui Mao, Zhi-Ren Liu, Jenny J Yang. PEGylation of protein-based MRI contrast agents improves relaxivities and biocompatibilities. Journal of inorganic biochemistry. 2012 Feb;107(1):111-8

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PMID: 22178673

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