Dual-mode MRI/CT Contrast Agents Based On DOTA-Branched Dendrimers

Molecular imaging technology has experienced a development process from low resolution to high resolution,low sensitivity to high sensitivity,and single modal imaging to multimodal imaging mode.A variety of imaging modes have been put into clinical use and are playing an increasingly important role in the diagnosis,treatment and monitoring of diseases.As the advancement of technology and instrument,the demand for real-time and accurate diagnosis is increasing.The limitations of single modal imaging has brought opportunities for the development of multimodal imaging techniques and instruments.More multimodal molecular imaging probes are under active development to improve the visibility and accuracy of clinical diagnosis.In this thesis,we focused on constructing imaging probes dendritic molecules.We synthesized multiple probes based on poly-1,4,7,10-tetraazacyclododecane-1,4,7,10tetraacetic acid(PDOTA)via surface modification and bimetallic chelation,and studied their application for magnetic resonance imaging(MRI)and X-ray computed tomography imaging(CT).In the first chapter,the research background is introduced.This chapter briefly describes the principles of magnetic resonance imaging,computed tomography and related molecular probes.The concepts and prospects of.dendrimers,multimodal imaging and multimodal imaging probes are also discussed.In the second chapter,we studied the performance of a PDOTA-based imaging probe Gd-G2-PEG for MRI.Using the strategies of surface modification and stepwise metal chelation,we synthesize Gd-G2-PEG and explore its performance for MRI.The experiments demonstrate that its outperforms Gd-DOTA in MRI with excellent biocompatibility.Its application for MRI of tumor-bearing mice is also explored.In the third chapter,we design and synthesize double metal chelate Gd&BiPDOTA-G2 based on PDOTA and explore its performance for MRI and CT.Aseries of experiments have illustrated that Gd&Bi-PDOTA-G2 is superior to gadodiamide under different magnetic field strengths for phantom MRI and in vivo MRI of rat.Its CT value is twice as high as iohexol and its CT performance is comparable to iohexol.All experiments show that Gd&Bi-PDOTA-G2 is a potential contrast agents for multimodal imaging.To sum up,we build two kinds of high-performance contrast agents based on PDOTA,which are utilized for MRI and MRI-CT,respectively.PDOTA-based imaging probes are not only of excellent biocompatibility,but also of outstanding imaging performance.The strategies of surface modification and stepwise chelation will provide more technical proposals for the construction of PDOTA-based molecular probes and inspire the development of a variety of molecular imaging.