Application of 18FFDG PET for Monitoring the Therapeutic Effect of Antiinflammatory Drugs on Stabil.docx
- 文档编号:27942154
- 上传时间:2023-07-06
- 格式:DOCX
- 页数:18
- 大小:95.59KB
Application of 18FFDG PET for Monitoring the Therapeutic Effect of Antiinflammatory Drugs on Stabil.docx
《Application of 18FFDG PET for Monitoring the Therapeutic Effect of Antiinflammatory Drugs on Stabil.docx》由会员分享,可在线阅读,更多相关《Application of 18FFDG PET for Monitoring the Therapeutic Effect of Antiinflammatory Drugs on Stabil.docx(18页珍藏版)》请在冰豆网上搜索。
Applicationof18FFDGPETforMonitoringtheTherapeuticEffectofAntiinflammatoryDrugsonStabil
Applicationof18F-FDGPETforMonitoringtheTherapeuticEffectofAntiinflammatoryDrugsonStabilizationofVulnerableAtheroscleroticPlaques
MikakoOgawa1,2,YasuhiroMagata1,TakashiKato2,KentaroHatano2,SeigoIshino3,TakahiroMukai4,MasashiShiomi5,KengoIto2andHideoSaji3
1LaboratoryofGenomeBio-PhotonicsPhotonMedicalResearchCenter,HamamatsuUniversitySchoolofMedicine,Hamamatsu,Japan;2DepartmentofBrainScienceandMolecularImaging,NationalInstituteforLongevitySciences,NationalCenterforGeriatricsandGerontology,Obu,Japan;3DepartmentofPatho-FunctionalBioanalysis,GraduateSchoolofPharmaceuticalSciences,KyotoUniversity,Kyoto,Japan;4DepartmentofChemo-PharmaceuticalSciences,GraduateSchoolofPharmaceuticalSciences,KyushuUniversity,Fukuoka,Japan;and5InstituteforExperimentalAnimals,KobeUniversitySchoolofMedicine,Kobe,Japan
Correspondence:
Forcorrespondenceorreprintscontact:
HideoSaji,PhD,DepartmentofPatho-FunctionalBioanalysis,GraduateSchoolofPharmaceuticalSciences,KyotoUniversity,Sakyo-ku,Kyoto606-8501,Japan.E-mail:
hsaji@pharm.kyoto-u.ac.jp
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
MATERIALSANDMETHODS
RESULTS
DISCUSSION
CONCLUSION
References
Theruptureofatheroscleroticvulnerableplaquesandsubsequentformationofthrombiarethemainfactorsresponsibleformyocardialandcerebralinfarctions.Becausemacrophageinfiltrationplaysanessentialroleinplaquerupturing,pharmacologictherapythatreducesmacrophageinfiltrationisrequiredtostabilizethevulnerableplaques.Themonitoringoftherapeuticeffectisimportantinassessingthetherapeuticeffectsofdrugsforindividualpatients.Wepreviouslyreportedthat18F-FDGaccumulatesinmacrophage-richplaques.Thepresentstudywasundertakentoinvestigatetheusefulnessof18F-FDGPETformonitoringtherapiesthattargetvascularinflammation.Methods:
Myocardialinfarction–proneWatanabeheritablehyperlipidemicrabbitswereusedinthisstudy.Theantioxidantprobucolwasincludedinthedietfedto4rabbitsstartingat10moofage(probucolgroup).Inacontrolstudy,4rabbitsreceivedstandardrabbitchow(controlgroup).18F-FDGPETexperimentswereperformedonbothgroupsbeforethestudyandat1,3,and6moaftertreatment.Afterthelastimagingsession,therabbitsweresacrificedat3hafterinjectionof18F-FDG,andtheaortaswereremoved.Theaccumulatedradioactivitywasthenmeasured,andthenumberofmacrophageswasdeterminedbyexaminationofstainedsections.Results:
Attheageof10mo,beforethetreatment,theaortacouldbeimagedby18F-FDGPETinallrabbits.Theaortacouldnotbeimagedafter6moofprobucoltreatment,whereasintenseradioactivitywasobservedinthecontrolrabbitsthroughouttheinvestigation.Thestandardizeduptakevalues(SUVs)oftheaortaweredecreasedsignificantlyintheprobucolgroupafter3moofinterventionascomparedwiththepretreatmentperiod.TheSUVsofthecontrolgroupwereincreasedgraduallyat6mo.Radioactivityintheaortawassignificantlylowerintheprobucolgroupthanthatinthecontrolgroup.Macrophageswerealreadypresentatthebeginningofthestudy,andprobucoltreatmentfor6moresultedinasignificantreductionofmacrophageinfiltration.Conclusion:
18F-FDGPETwasabletoimagethereductionofinflammationbyprobucol.18F-FDGPETshouldbeusefulforevaluatingthetherapeuticeffectofdrugsclinicallyandforthedevelopmentofnewdrugsthatcanstabilizevulnerableplaques.18F-FDGPETshouldbeusefulforevaluatingthetherapeuticeffectofdrugsclinicallyandforthedevelopmentofnewdrugsthatcanreduceinflammationofvulnerableplaques.
KeyWords:
18F-FDGPET•atherosclerosis•vulnerableplaque•therapeuticeffect•probucol
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
MATERIALSANDMETHODS
RESULTS
DISCUSSION
CONCLUSION
References
Theruptureofatheroscleroticplaqueandensuingthrombusformationareprimarilyresponsibleformyocardialandcerebralinfarctions(1–3).Atheroscleroticplaquesareclassifiedinto2types,stableandvulnerable,withthelatterhavingahighriskofrupture.Thus,thedetectionofatheroscleroticplaquespronetoruptureisclinicallyimportantforriskstratificationandtoprovideearlytreatment.Inflammationplaysanessentialroleinplaquerupturing,andmacrophageinfiltrationischaracteristicofthevulnerableplaques(4).Recently,weandanothergrouphaveshownthat18F-FDGaccumulatesinmacrophage-richplaques,and18F-FDGPEThasbeensuggestedtobeusefulfortheselectivedetectionofvulnerableplaques(5–7).
Manydrugshavebeentestedfortheirabilitytostabilizeplaque(8),andmacrophagesareoneofthetargetsofthesepharmacologictherapies(9).However,becausedrugeffectsvaryamongindividuals,monitoringthetherapeuticeffectisimportantforselectingtheappropriatedrugforindividualpatients.Thepresentstudywasundertakentoinvestigatetheusefulnessof18F-FDGPETformonitoringtherapiesthattargetvascularinflammation.WeusedprobucolinWatanabeheritablehyperlipidemicrabbitswithmyocardialinfarction(WHHLMIrabbits)(10)—awidelyusedanimalmodelofatherosclerosis(11,12)—becauseprobucolisanantioxidantknowntoreducetheextentofmacrophageinfiltrationinatheroscleroticlesionsintheserabbits(13).TheatheroscleroticplaqueofWHHLMIrabbitsdoesnotrupturebutitspathologiccharacteristicshavebeenreportedtoresemblethoseofthehumanlesion(10,14,15).
MATERIALSANDMETHODS
TOP
ABSTRACT
INTRODUCTION
MATERIALSANDMETHODS
RESULTS
DISCUSSION
CONCLUSION
References
AnimalsandDiets
PureprobucolpowderwaskindlysuppliedbyDaiichiPharmaceuticalCo.Ltd.WHHLMIrabbitsbredatKobeUniversitywereusedinthisstudy.Theanimalswerefedstandardrabbitchow(typeRC4;OrientalYeastCo.,Ltd.)untiltheageof10mo.Onerabbitwaskilledunderanesthesiawithsodiumpentobarbital,andtheaortawasremovedatthebeginningoftheexperimenttobeusedasapretreatmentcontroltoinvestigateatheroscleroticlesionsoftheaorta.Otherrabbitsweredividedinto2groups.Fourrabbitswerefedchow(130g/d)containing1%(w/w)probucolfor6mo(probucolgroup).Wechosethisdoseaccordingtopreviouslypublishedmethods(16–19),althoughthisdoseisabout20timeshigherthantherecommendedhumandose.Fourrabbitsinthecontrolgroupweregivenstandardrabbitchow(130g/d)for6mo.Waterwasavailableadlibitumforallrabbits.Beforedrugtreatmentandat1,3,and6moafterdrugadministration,bodyweightandplasmalevelsoftotal,low-densitylipoprotein(LDL),andhigh-densitylipoprotein(HDL)cholesterolandtriglycerideswereevaluated.TheAnimalCareandUseCommitteeoftheHamamatsuUniversitySchoolofMedicineapprovedallexperiments.
PETandCT
Theanimalswerefastedforatleast6hbeforereceiving18F-FDG.Beforetheimagingstudy,theindividualbodyshapewastakenwithurethanehardeningfoamtomaintainthestereotacticposition.18F-FDGPETandCTexperimentswereperformedat10moofageandafter1,3,and6moofinterventioninbothgroupsaccordingtoapreviouslyreportedmethodwithslightmodification(5).Briefly,therabbitswereanesthetizedand18F-FDG(37–185MBq)wasinjectedintoamarginalearvein.PETwasperformedfor15minat180minafterinjectionof18F-FDGusinganECATEXACTHRPETscanner(SiemensAG).WechosethistimepointaccordingtothemethodofTawakoletal.(6).AfterthePETstudy,aCTangiogramwasacquiredwithanX-forceCTscanner(ToshibaMedicalCorp.)usingiohexolasacontrastagent.PETimageswerecalibratedtotheinjecteddoseof18F-FDG.Formeasurementofradioactivityinthethoracicaorta,4circularregionsofinterests(ROIs)(3mm2foreachROI)weredrawnontheaorta.Theanalysiswasundertakenwithnoknowledgeoftheanimalgroup.Thestandardizeduptakevalue(SUV)wascalculatedbydividingthetissueconcentration(kBq/mL)bytheinjecteddosepergramofbodyweight(kBq/g).
18F-FDGBiodistributionStudy
ThebiodistributionstudywasperformedonthedayaftertheCTandPETstudy,6moafterprobucoladministration.Therabbitswereanesthetizedand18F-FDG(370MBq)wasinjectedintoamarginalearvein.Threehoursafterthe18F-FDGinjection,theanimalsweresacrificedwithanoverdoseofsodiumpentobarbital.PerfusionfixationwasthenperformedusingPLPsolution(75mmol/LL-(+)-lysinehydrochlorideand4%paraformaldehydein37.5mmol/Lphosphatebuffer,pH7.4).Thethoracicandabdominalaortasweresubsequentlyremoved,cutinto10-mmsegments,andweighed.ThesegmentswereimmediatelypostfixedinPLPsolution,andradioactivitywasmeasuredwithawell-type
-counter(COBRA;PackardCo.Ltd.).Theresultsareexpressedasthedifferentialuptakeratio(DUR):
Histology
Eacharterialsegmentwasembeddedinparaffinaftertheradioactivitywasmeasured.Consecutive4-µm-thicksectionswerepreparedfromeachsegmentandthesectionsweresubjectedtoimmunohistochemicalstainingorazan-Mallorystaining.ImmunohistochemistrywasperformedaccordingtothemethodreportedbyTsukadaetal.usingtherabbitmacrophage-specificmonoclonalantibodyRAM-11(DakoCorp.)(20).Thesesliceswerealsocostainedwithhematoxylinforidentificationofthenucleus.ThenumberofmacrophageswasdeterminedbycountingthenucleiofRAM-11–positivecellsineachslice.Theintimaandwholeareaweremeasuredonanazan-Mallory–stainedconsecutivecros
- 配套讲稿:
如PPT文件的首页显示word图标,表示该PPT已包含配套word讲稿。双击word图标可打开word文档。
- 特殊限制:
部分文档作品中含有的国旗、国徽等图片,仅作为作品整体效果示例展示,禁止商用。设计者仅对作品中独创性部分享有著作权。
- 关 键 词:
- Application of 18FFDG PET for Monitoring the Therapeutic Effect Antiinflammatory Drugs on Stabil 18
链接地址:https://www.bdocx.com/doc/27942154.html