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»ã±¨±êÌâ(Ó¢ÎÄ)£ºMolecular Imaging Agents Responsive to In Vivo Signals
»ã±¨ÈËÐÕÃû£ºAndrew K. Whittaker
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»ã±¨È˼ò½é(ÖÐÎÄ)£ºAndrew Whittaker½ÌÊÚÏÖÈΰĴóÀûÑÇ×êÑÐÀíÊ»á×ÊÉî½ÌÊÚ×êÑÐÔ±£¬ÊǰĴóÀûÑÇÀ¥Ê¿À¼´óѧÉúÎ﹤³ÌºÍÄÉÃ×¼¼Êõ×êÑÐËù£¨AIBN£©¼°¸ß¼¶³ÉÏñÖÐÐÄ£¨CAI£©µÄѧÊõ´øÍ·ÈË¡£ËûÖÂÁ¦ÓÚ×êÑиߵµ¸ß·Ö×Ó»¯Ñ§ÒÔ½â¾ö¿Æ¼¼ºÍ½¡È«ÁìÓòµÈ³ÁÒªÎÊÌâ¡£Ä¿Ç°ÖØÒª×êÑеÄÀûÓÃÁìÓòÔ̺¬£º1£©ÓÃÓÚ²¡±ä×éÖ¯¼ø±ð¡¢Ò©Î↑ÊÍ¡¢×éÖ¯ÔÙÉúµÄ¾ÛºÏÎïºÍÄÉÃ××ÊÁÏ £»2£©ÓÃÓÚÏȽø¹â¿Ì¼¼ÊõµÄ¾ÛºÏÎï £»3£©ÏÖ´úºË´Å¹²Õñ¼°³ÉÏñµÄ×ÊÁϱíÕ÷¡£ËûµÄÍŶÓÔÚ»¯Ñ§ºÏ³É¡¢ÎïÀí»¯Ñ§ºÍ×ÊÁϱíÕ÷µÈÁìÓò¾ùÓкܸßÔìÒ衣ĿǰËû¸¨µ¼×ÅÒ»Ö§Ô¼40Ãû×êÑÐÈËÔ±µÄ¿ÎÌâ×飬×êÑÐÁìÓòÉæ¼°¸ß·Ö×Ó»¯Ñ§µÄ¶à¸ö·½Ãæ¡£Whittake½ÌÊÚÊÇÉýƽÑó¸ß·Ö×Ó½áºÏѧ»áµÄǰÈÎÖ÷ϯ¡¢°Ä´óÀûÑǻʼһ¯Ñ§»ã¾ÛºÏÎﲿµÄǰÈÎÖ÷ϯ¡¢°Ä´óÀûÑǸ߷Ö×Óѧ»áµÄÖ÷ϯ£¬Í¬Ê±Ò²ÊǶà¸ö¹ú¼Ê¿ÆÑ§Î¯Ô±»áµÄ³ÉÔ±¡£ËûµÄ¶à¶à½±ÏîÖÐÔ̺¬2013ÄêºÍ2014ÄêÓÉÖйú±í¹úר¼Ò¾ÖºË×¼µÄ¸ß¶Ë±í¹úר¼ÒÏîÄ¿¡£ÔÚ´ÓǰµÄÊ®ÄêÀïËû¹²»ñµÃ³¬¹ý4000Íò°ÄÔª£¨´óÓÚ2ÒÚÈËÃñ±Ò£©µÄ¿ÆÑо­·Ñ£¬ÔÚ¹ú¼Ê³ÛÃûÔÓÖ¾¹«¿ª°ä·¢ÎÄÕ³¬¹ý265ƪ¡£×ÜÖ®£¬Andrew Whittaker½ÌÊÚÒѾ­Ôڸ߷Ö×Ó»¯Ñ§ºÍºË´Å¹²ÕñÁìÓò¹¤×÷ÁË25ÄêÖ®¶à¡£
»ã±¨ÄÚÈݼò½é£ºRecently there has been intense interest in the development of fluorinated molecules to allow tracking of therapeutic particles and cells in vivo. The motivation for this is the very high selectivity of the 19F imaging experiment, since unlike in 1H NMR imaging, the body does not contain a confounding fluorine background signal. In principle therefore, if doubly-tuned MRI coils are available, highly-selective 19F images can be superimposed on high-resolution anatomical 1H images, thus allowing tracking of suitably-labelled cells or biomarker molecules. In this presentation I will describe the current status of magnetic resonance imaging agents with a focus on polymeric agents. This will define the motivation for the development of new partly-fluorinated copolymers which have outstanding potential as 19F MRI imaging agents.1,2,3 In this paper we describe the development of several new classes of polymeric 19F MRI agents with precisely controlled architecture and functionality. In the first generation of materials, amphiphilic copolymers PAA-b-p(nBA-stat-TFE(M)A) were prepared by ATRP of trifluoroethyl (meth)acrylate and n-butyl acrylate using PtBA as macroinitiator, followed by acidolysis in TFA/DCM. The block copolymers were micellized by slow addition of water from various solvents. MRI properties were measured for all systems and the relationship between structure and performance determined.1,3 The second generation materials2,4 arising from these studies are hyperbranched analogues constructed from similar monomers and made highly branched by incorporation of a crosslinking monomer during RAFT (or ATRP) synthesis. Excellent imaging performance was observed. More recently we have developed a series of linear, branched and star molecules incorporating the monomers N,N-dimethylaminoethyl methacrylate and poly(ethylene glycol) methacrylate which are responsive to external stimuli, for example local temperature, pH or ionic strength.5-7 Details of application of these systems to a range of important diseases, such as melanoma, prostate cancer and malignant glioma will be presented.
 
 
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