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Calix[4]arenesasMolecularPlatformsforMagneticResonanceImaging
(MRI)ContrastAgentsThePaperOutlineConclusion3Introduction1Experimental
Section
21、IntroductionMolecularimaging
Itseemstotakephotosofmolecular,displaythemorphologicalstructureofourtarget.
Inotherwords,characterizationandmeasurementoftheprocessoflivinganimals,humanbiologyandmodelsysteminthecellularandmolecularlevelusingtheimagingdetectorinvitro.FeaturesofmolecularimagingNon-invasiveimagingtechniqueDynamicacquisitionReflectfull-scaleSomemainimagingtechniques
Positronemissiontomography(PET)Singlephotonemissioncomputedtomography(SPECT)Magneticresonanceimaging(MRI)Ultrasonicimaging
Opticalimaging(Bioluminescence,Fluorescence)MRIMagneticresonanceimaging(MRI)isoneofthemostimportanttechniquesinmedicalimaging.Itisnoninvasive,avoidsproblemsoccurringinotherimagingtechniquessuchasscattering(opticalimaging)orhigh-energyradiation(computedtomography(CT)orX-ray),andenablestheproductionof3Dimagesofvarioustissues.Thechallengeistopreparecomplexesthatdonotreleasethetoxicmetalioninvivoandyetareefficientcontrastagents.2、ExperimentalSectionThecontrastisgeneratedbydifferencesineithertheprotondensitybetweentissuesand/ordifferencesinT1orT2relaxationtimes.Anoncovalentapproachistoprepareamphiphiliccompoundsthatformaggregates.Targetedcontrastagentsusuallyhavehigherrelaxivitieswheninteractingwiththetargetduetotherestrictionoftherotationalmotionuponbinding.InMRIanongoingtrendistoapplyhighermagneticfieldstrengths(>1.5T).ThiscanbeachievedbyoptimizingtheaveragewaterresidencelifetimetMtoevenshortervaluesthanthatpredictedof20–40nsforhighmolecularweightagents.OneofapproachestofindsystemswithoptimalτRistousetheratherrigidcalix[4]arenecoreasasyntheticplatform.Calixarenesgenerallyenabletheintroductionofatleasttwodifferentfunctions.
AggregationVariable-temperature17ONMRmeasurementsWithintheexperimentalerror,thehyperfinecouplingconstantisidenticaltocommonlyobservedvaluesforoxygenatomsdirectlycoordinatedtoGd.NuclearmagneticrelaxationdispersionNMRDisapowerfultechniqueforcharacterizingMRIcontrastagents.NMRDprofilesshowtherelaxivityofthemonomertobealmostindependentofthemagneticfieldstrengthupto60MHz.InteractionwithHASIthasbeenshownpreviouslythatcalix[4]arenescaninteractwiththehydrophobictransportproteinHSA,duetotheirapolarstructure.TheaffinityofhydrophobiccompoundswithHSAisanongoingtopicinmodernMRIresearchsincebothrelaxivityandpharmacokineticscanbecontrolledbynoncovalentbindingofcontrastagentstoHSA.Tocompareourresultswithliteraturedataoncalixarene-basedGdcomplexesinteractingwithHSA,wefollowedtheproceduredescribedforthesesystemsandassumedthatthereis,effectively,onlyasinglebindingsiteinHAS.WealsoperformedNMRDmeasurementsat37℃onasolutioncontaining4%HSA(0.6mm)and1(0.47mm).Theelectronicparametersareinthesamerangeasthoseofthemicellaraggregatesandofthemonomer.3、ConclusionThenovelnonchargedself-aggregatingcalix[4]arene-basedMRIcontrastagentdescribedhereexhibitsgoodrelaxivitiesoverabroadrangeofLamorfrequencies.Evaluationoftheparametersgoverningtherelaxivityshowsthatitislimitedbytheaverageresidencetimeofwaterinthefi
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