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000824536 005__ 20210129225049.0
000824536 037__ $$aFZJ-2016-07108
000824536 041__ $$aEnglish
000824536 1001_ $$0P:(DE-Juel1)157673$$aPetina, Olga$$b0
000824536 1112_ $$aBeing Smart In Coordination Chemistry: Medical Applications$$cOrleans$$d2016-09-26 - 2016-09-28$$wFrance
000824536 245__ $$aNOTA- and DOTA-coated gold nanoparticles for bimodal PET-MR molecular imaging
000824536 260__ $$c2016
000824536 3367_ $$033$$2EndNote$$aConference Paper
000824536 3367_ $$2BibTeX$$aINPROCEEDINGS
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000824536 3367_ $$0PUB:(DE-HGF)24$$2PUB:(DE-HGF)$$aPoster$$bposter$$mposter$$s1481021216_22561$$xPlenary/Keynote
000824536 520__ $$aBimodal hybrid PET-MR imaging offers as valuable and promising tool for non-invasive diagnosis ofvarious diseases as it benefits from the advantages of both individual imaging modalities, i.e. thesuperb soft tissue contrast of MRI combined with the excellent sensitivity and ability of quantificationof PET. With hybrid PET-MR scanners already available, the development of suitable bimodal PET-MRimaging agents is essential. Those molecular probes will provide better morphological correlation ofmolecular function, biomarker-responsive imaging and time-saving “PET-guided” high-resolutionMRI.For this purpose, gold nanoparticle (Au-NP) based bimodal contrast agents were designed. Incontrast to small organic molecules with a limited number of attachment points, nanoparticles (NPs)can be loaded with various ligands in the required ratio. This allows to overcome the mismatch ofconcentrations of the imaging probes which are required for PET and MRT measurements,respectively. The GdDOTA complex was chosen as MRI-reporting moiety due to its highthermodynamic stability and kinetic inertness which are very important properties for the in vivoapplication of Gd-loaded NPs with an enhanced time of circulation in the body.The very challenging synthesis of a DOTA-like chelator with a thiol anchoring group for the directcovalent immobilization on the gold surface was carried out using the “bisaminal route”. Startingfrom triethylenetetramine, a DOTA_OH-tBu4 ester was obtained, according to some optimization of adescribed procedure1. The O-alkylation of DOTA_OH-tBu4 ester with thiol-bearing electrophiles,which was followed by deprotection, led to the DOTA derivatives L1 and L2 with the thiol handlebeing directly attached to the macrocyclic backbone. The thiol-containing NOTA L3 for radiolabelingof Au-NPs with the PET radionuclide 68Ga was directly obtained from a commercially available NODAGA-NHS ester through reaction with cysteamine.Citrate-stabilized Au-NPs with d ≈ 13 nm were prepared by citrate reduction of HAuCl4 and thenfunctionalized with thiol-ending chelators by a ligand place exchange reaction. The DOTAfunctionalizedAu-NPs formed the corresponding complexes Au@GdL1 and Au@GdL2 with Gd ionswhich were tested for their potential as contrast agents. As expected, the paramagnetic Au-NPsshowed an increased relaxivity (36-39 mM-1s-1, 25°C, 20 MHz) compared with their small molecularanalogues GdL1/Gd2L22 (4-12 mM-1s-1, 25°C, 20 MHz). After that the mixture of DOTA and NOTAchelating agents were grafted to the gold surface. The difference in cavity size of NOTA and DOTAshould lead to a selective complex formation of Au@DOTA-NOTA first with paramagnetic Gd andthen with radioactive 68Ga,2 forming thereby a bimodal PET-MR imaging agent.
000824536 536__ $$0G:(DE-HGF)POF3-573$$a573 - Neuroimaging (POF3-573)$$cPOF3-573$$fPOF III$$x0
000824536 7001_ $$0P:(DE-Juel1)131818$$aErmert, Johannes$$b1$$eCorresponding author$$ufzj
000824536 7001_ $$0P:(DE-Juel1)131816$$aCoenen, Heinrich Hubert$$b2
000824536 7001_ $$0P:(DE-Juel1)166419$$aNeumaier, Bernd$$b3
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000824536 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)157673$$aForschungszentrum Jülich$$b0$$kFZJ
000824536 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131818$$aForschungszentrum Jülich$$b1$$kFZJ
000824536 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131816$$aForschungszentrum Jülich$$b2$$kFZJ
000824536 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)166419$$aForschungszentrum Jülich$$b3$$kFZJ
000824536 9131_ $$0G:(DE-HGF)POF3-573$$1G:(DE-HGF)POF3-570$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lDecoding the Human Brain$$vNeuroimaging$$x0
000824536 9141_ $$y2016
000824536 915__ $$0StatID:(DE-HGF)0550$$2StatID$$aNo Authors Fulltext
000824536 920__ $$lyes
000824536 9201_ $$0I:(DE-Juel1)INM-5-20090406$$kINM-5$$lNuklearchemie$$x0
000824536 9201_ $$0I:(DE-Juel1)INM-4-20090406$$kINM-4$$lPhysik der Medizinischen Bildgebung$$x1
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