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Purpose: PresentcommercialMRcontrastagentslackofspecificity,bearthehighrisksofmisseddiagnosisorincomplete resectionofglioma.Theaimofthisstudywastoinvestigatethepossibilityofusingbiotin-conjugateduperconversion nanoparticles(UCNPs)forMagneticResonance/UpconversionLuminescenceimagingofgliomaforefficientdetectionofglioma. Methods and Materials:C6cells(1×106/lsuspendedinPBS)wereimplantedintothestriatum(3.0mmlateral,1.0mmanteriorto bregma)ofmalerats(150±10kg)byusingastereotacticfixationdevicewithratsadapter.Theintracranialglioma-bearingmice werereadyforimagingafterinoculationforfivedays.T1-weightedMRimagesofglioma-bearingmicebrainwerecollected beforeand10min,0.5,1,2,8,24,48hafteradministrationofBiotin/PEG-UCNPsandPEG-UCNPswithadoseof2ml(6mg Mn/kgdose)viaintravenousinjection.Andtumorregionsofinterest(ROI)withthesamecircularareawerecarefullyselectedon T1-weightedMRimagesbeforeandafterinjectionaccordingtothepreviousT2-weightedimagesdelineation.Thesignalintensity(SI)ofROIinthebraintumorwasthenmeasured.Theupconversionluminescenceimagingwasappliedtobecorrelatedwith pathologicalfindingstoinvestigatetherealdelineationofglioma. Results:T1-weightedMRcontrastofthegliomainthetargetinggroupwassignificantlyenhancedandthetumorboundarywas alsomuchmoreclearlydelineatedascomparedtothenontargetinggroup.Thetumor-targetingbehaviorsoftheBiotin/PEGUCNPs couldbemoreclearlyobservedfromthequantitativeanalysisontheSIoftumorarea.Ingeneral,theaverageSIofthe tumorregionbegantoincreaseimmediatelyaftertheinjectionofBiotin/PEG-UCNPs,reachingamaximal63.1%enhancementin 1hafterinjection,duetotheirhighlyefficienttumortargeting,andmaintainedforalongtimeperiod(morethan2h). Comparatively,thePEG-UCNPsadministrationshowedalimitedmaximalcontrastenhancementbyabout26.2%in30min,with shortretentiontime.Overall,theMRimagesandthecorrespondingbraintumorSIenhancementdataevidencevalidatedthe specificityofBiotin/PEG-UCNPstoC6biotinreceptorinvivo.Inthetargetinggroup,theupconversionluminescenceimaging confirmedthattheinvivolocalizationofbiotin-conjugatedUCNPswaswellcorrelatedwithpathologicalfindings. Conclusion:Insummary,Biotin/PEG-UCNPswithimprovedlongitudinalrelaxivityaspotentialglioma-targetedT1contrastagents weresynthesizedandcharacterized.TheinvivoMRimagingdemonstratedthatBiotin/PEG-UCNPsexhibitedanenhanced contrasteffectintheearlystagegliomaregionwithaprolongedimagingperiod.Moreover,Biotin/PEG-UCNPsledtoaclearer marginofglioma.ThistogetherwiththegoodbiocompatibilitymakesBiotin/PEG-UCNPsapromisingT1contrastagentfor betterdetectionanddelineationofbraingliomasattheearlystage.