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1、The Paper,Outline,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 animals,human biology and model system in the cellular and molecular level using the imag
2、ing detector in vitro.Features of molecular imaging Non-invasive imaging technique Dynamic acquisition Reflect full-scale,Some main imaging techniques Positron emission tomography(PET)Single photon emission computed tomography(SPECT)Magnetic resonance imaging(MRI)Ultrasonic imaging Optical imaging(B
3、ioluminescence,Fluorescence),MRIMagnetic resonance imaging(MRI)is one of the most important techniques in medical imaging.It is noninvasive,avoids problems occurring in other imaging techniques such as scattering(optical imaging)or high-energy radiation(computed tomography(CT)or X-ray),and enables t
4、he production of 3D images of various tissues.,The challenge is to prepare complexes that do not release the toxic metal ion in vivo and yet are efficient contrast agents.,2、Experimental Section,The contrast is generated by differences in either the proton density between tissues and/or differences
5、in T1 or T2 relaxation times.A noncovalent approach is to prepare amphiphilic compounds that form aggregates.Targeted contrast agents usually have higher relaxivities when interacting with the target due to the restriction of the rotational motion upon binding.,In MRI an ongoing trend is to apply hi
6、gher magnetic field strengths(1.5 T).This can be achieved by optimizing the average water residence lifetime tM to even shorter values than that predicted of 2040 ns for high molecular weight agents.,One of approaches to find systems with optimal R is to use the rather rigid calix4arene core as a sy
7、nthetic platform.Calixarenes generally enable the introduction of at least two different functions.,Aggregation,Variable-temperature 17O NMR measurementsWithin the experimental error,the hyperfine coupling constant is identical to commonly observed values for oxygen atoms directly coordinated to Gd.
8、,Nuclear magnetic relaxation dispersion NMRD is a powerful technique for characterizing MRI contrast agents.NMRD profiles show the relaxivity of the monomer to be almost independent of the magnetic field strength up to 60 MHz.,Interaction with HASIt has been shown previously that calix4arenes can in
9、teract with the hydrophobic transport protein HSA,due to their apolar structure.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.,To compare our resu
10、lts with literature data on calixarene-based Gd complexes interacting 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).,T
11、he electronic parameters are in the same range as thoseof the micellar aggregates and of the monomer.,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.,Investigations to further improve the efficiency of calix4arene-based MRI contrast agents along these lines are in progress.,Thanks for your attention!,
