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1、May2005MolecularImaging–EmergingTechniquesandStagingofProstateCancerMichaelPacold,HMSIIIGillianLieberman,MDMichaelPacold,HMSIII1GillianLieberman,MDNonNova...SedNovae(NotNewThings,butThingsDoneNewly)•MolecularImaging:definedasvisualizationofauniqueprocessinvivo,usingaspecificpro
2、beandimagingmodality•Notanewfield:sameprincipleasNuclearMedicine,butmorespecific•Maybeviewedasa“SpecialStain”fortheRadiologistMichaelPacold,HMSIII2GillianLieberman,MDResearchapplication:ImagingaPlaqueintheBrain•Alzheimer’sdisease:4millioncasesinUS•Atpresent,nodrugstopreventordi
3、sruptplaqueformation•Diseaseevaluationrequiresneuropathology•Invivoplaquedetectionusefulfordrugdevelopment(wouldallowrapiddetectionofplaquesinexperimentalanimals)MichaelPacold,HMSIII3GillianLieberman,MDAnInvivoCongoRed+NaSO-3ONONNNH2NH2NON-NBFN4+AOI-987SO-Na3CongoRedModality:Op
4、tical(Near-InfraredFluorescence)MichaelPacold,HMSIII4Hintersteineretal.,Nat.Biotech2005,23,577-583GillianLieberman,MDAlzheimer’splaquesinamouse30min.240min.APP23+AOI-987(Fluorescencevisibleat240min.)WildType+AOI-987(nofluorescenceat240min.)APP23+Saline(nofluorescence)MichaelPac
5、old,HMSIII5Hintersteineretal.,Nat.Biotech2005,23,577-583GillianLieberman,MDTranslationalapplication:ImagingaPlaqueintheAorta•CoronaryArteryDisease:~500,000deaths/year•Conventionalimagingassessescalcificationanddegreeofstenosis–butnotriskofplaquerupture•Vulnerableplaquecannotbei
6、magedatpresent–buthashighlevelsofinflammatorycellandproteaseactivitythatmightbeimagedMichaelPacold,HMSIII6GillianLieberman,MDAnactiveprobeforCathepsinBPEG-OMePEG-OMePEG-OMePEG-OMeLysLysLysLysLysLys*LysLysLys+Lys*CathepsinBnCy5Cy5Cy5Cy5QuenchedFluorescentNNModality:Near-Cy5=infr
7、aredfluorescenceOHRMichaelPacold,HMSIII7Chenetal.,Circulation2002,105,2766-2771GillianLieberman,MDCathepsinBactivity–invivoMRIFluorescence-mediatedtomography-showsactiveCathepsinBMichaelPacold,HMSIII8Chenetal.,Circulation2002,105,2766-2771GillianLieberman,MDLymphNodeImagingforP
8、rostateCancer•~200,000diagnoses/year;~30,000deaths•Two
