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1、磁共振成像第1 页，本讲稿共19 页The Paper第2 页，本讲稿共19 页OutlineConclusion3Introduction1Experimental Section 2第3 页，本讲稿共19 页1、Introduction Molecular imaging It seems to take photos of molecular,display the morphological structure of our target.In other words,characterization and measurement of the process of living a
2、nimals,human biology and model system in the cellular and molecular level using the imaging detector in vitro.Features of molecular imaging Non-invasive imaging technique Dynamic acquisition Reflect full-scale第4 页，本讲稿共19 页 Some main imaging techniques Positron emission tomography(PET)Single photon e
3、mission computed tomography(SPECT)Magnetic resonance imaging(MRI)Ultrasonic imaging Optical imaging(Bioluminescence,Fluorescence)第5 页，本讲稿共19 页MRI Magnetic resonance imaging(MRI)is one of the most important techniques in medical imaging.It is noninvasive,avoids problems occurring in other imaging tec
4、hniques such as scattering(optical imaging)or high-energy radiation(computed tomography(CT)or X-ray),and enables the production of 3D images of various tissues.第6 页，本讲稿共19 页 The challenge is to prepare complexes that do not release the toxic metal ion in vivo and yet are efficient contrast agents.第7
5、 页，本讲稿共19 页2、Experimental Section The contrast is generated by differences in either the proton density between tissues and/or differences in T1 or T2 relaxation times.A noncovalent approach is to prepare amphiphilic compounds that form aggregates.Targeted contrast agents usually have higher relaxiv
6、ities when interacting with the target due to the restriction of the rotational motion upon binding.第8 页，本讲稿共19 页 In MRI an ongoing trend is to apply higher magnetic field strengths(1.5 T).This can be achieved by optimizing the average water residence lifetime tM to even shorter values than that pre
7、dicted of 2040 ns for high molecular weight agents.第9 页，本讲稿共19 页 One of approaches to find systems with optimal R is to use the rather rigid calix4arene core as a synthetic platform.Calixarenes generally enable the introduction of at least two different functions.第10 页，本讲稿共19 页 Aggregation第11 页，本讲稿共
8、19 页 Variable-temperature 17O NMR measurements Within the experimental error,the hyperfine coupling constant is identical to commonly observed values for oxygen atoms directly coordinated to Gd.第12 页，本讲稿共19 页 Nuclear magnetic relaxation dispersion NMRD is a powerful technique for characterizing MRI
9、contrast agents.NMRD profiles show the relaxivity of the monomer to be almost independent of the magnetic field strength up to 60 MHz.第13 页，本讲稿共19 页 Interaction with HAS It has been shown previously that calix4arenes can interact with the hydrophobic transport protein HSA,due to their apolar structu
10、re.The affinity of hydrophobic compounds with HSA is an ongoing topic in modern MRI research since both relaxivity and pharmacokinetics can be controlled by noncovalent binding of contrast agents to HSA.第14 页，本讲稿共19 页 To compare our results with literature data on calixarene-based Gd complexes inter
11、acting with HSA,we followed the procedure described for these systems and assumed that there is,effectively,only a single binding site in HAS.We also performed NMRD measurements at 37 on a solution containing 4%HSA(0.6mm)and 1(0.47mm).第15 页，本讲稿共19 页The electronic parameters are in the same range as
12、thoseof the micellar aggregates and of the monomer.第16 页，本讲稿共19 页3、Conclusion The novel noncharged self-aggregating calix4arene-based MRI contrast agent described here exhibits good relaxivities over a broad range of Lamor frequencies.Evaluation of the parameters governing the relaxivity shows that it is limited by the average residence time of water in the first coordination sphere of GdIII.第17 页，本讲稿共19 页 Investigations to further improve the efficiency of calix4arene-based MRI contrast agents along these lines are in progress.第18 页，本讲稿共19 页第19 页，本讲稿共19 页