Porphyrin-based high relaxivity MRI T1 contrast agents for biomedical imaging

点击翻译按钮获取中文摘要

As one of the major clinical imaging modalities, MRI can noninvasively penetrate deep into an intact, opaque object to provide interior 3D information with a high resolution, which has become one of the most powerful diagnostic tools for detecting diseases. It was estimated that almost 50% of clinical MRI scans nowadays used a MRI contrast agent (CA), a new class of pharmacological product which can enhance the contrast and sensitivity of MRI. The intrinsic low relaxivity (a term that defines the efficacy of MRI CA) for most T1 contrast agents has become a critical technical bottle-neck, limiting its broader application and potential in clinical medicine and biomedical research. The current proposal mainly aims to overcome the relaxivity limitation of T1 CA, using a systematic chemical approach based on a well-established Solomon-Bloembergen -Morgan theory, and to develop porphyrin-based high relaxivity T1 CAs with well-suited compatibility for biomedical applications. A series of porphyrin oligomers with systematically programmed chemical and physical parameters, including molecular size, molecular geometry and conformational rigidity, will be designed, synthesized and characterized. The influence of these variables on the T1 relaxivity, together with their pharmacokinetic properties and toxicity, will be investigated, to evaluate their efficacy and safety for biomedical application. In addition, the potential of using the diamagnetic version of these new porphyrin-oligomers for fluorescence imaging and photodynamic therapy (PDT) will also be examined. In this proposal, theoretical prediction, chemical synthesis, spectroscopic characterization, and biological evaluation will be strategically combined. The systematic structural-activity relationship obtained from current study will provide a guidance towards more rational design of MRI CAs in the future. Our long-term goal is to apply this new generation of T1 CAs, in combination with modern MRI technique and advanced molecular targeting strategy, to selectively and noninvasively detect disease, such as cancer, at early stage.