简介：Integrinανβ6isexpressedatanundetectablelevelinnormaltissues,butisremarkablyupregulatedduringmanypathologicalprocesses,especiallyincancerandfibrosis.Noninvasiveimagingofintegrinανβ6expressionusingaradiotracerwithfavorableinvivopharmacokineticswouldfacilitatediseasediagnosisandtherapymonitoring.Throughdisulfide-cyclizedmethod,wesynthesizedinthisstudy,anewintegrinανβ6-targetedcyclicpeptide(denotedascHK),andradiolabeleditwith99mTc.Theabilityoftheresultingradiotracer99mTc-HYNIC-cHKtodetectintegrinανβ6expressioninpancreaticcancerxenograffsandidiopathicpulmonaryfibrosiswasevaluatedusingsmall-animalsingle-photonemissioncomputedtomography(SPECT)/computedtomography(CT).99mTc-HYNIC-cHKshowedsignificantlyimprovedinvivometabolicstabilitycomparedtothelinearpeptide-basedradiotracer99mTc-HYNICHK.99mTc-HYNIC-cHKexhibitedsimilarbiodistributionpropertiesto99mTc-HYNIC-HK,butthetumorto-muscleratiowassignificantlyincreased(2.99±0.87vs.1.82±0.27,P<0.05).High-contrastimagesofintegrinανβ6-positivetumorsandbleomycin-inducedfibroticlungswereobtainedbySPECT/CTimagingusing99mTc-HYNIC-cHK.Overall,ourstudiesdemonstratethat99mTc-HYNIC-cHKisapromisingSPECTradiotracerforthenoninya-siveimagingofintegrinανβ6inlivingsubjects.