Permanent Occlusion of Feeding Arteries and Draining Veins in Solid Mouse Tumors by Vascular Targeted Photodynamic Therapy (VTP) with Tookad 英文参考文献.docVIP

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Permanent Occlusion of Feeding Arteries and Draining Veins in Solid Mouse Tumors by Vascular Targeted Photodynamic Therapy (VTP) with Tookad 英文参考文献.doc

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Permanent Occlusion of Feeding Arteries and Draining Veins in Solid Mouse Tumors by Vascular Targeted Photodynamic Therapy (VTP) with Tookad 英文参考文献

PermanentOcclusionofFeedingArteriesandDraining VeinsinSolidMouseTumorsbyVascularTargeted PhotodynamicTherapy(VTP)withTookad NoaMadar-Balakirski1,CatherineTempel-Brami1,VyacheslavKalchenko2,OriBrenner2,DavidVaron4, AvigdorScherz3.,YoramSalomon1*. 1Department ofBiological Regulation, TheWeizmann Institute ofScience,Rehovot,Israel, 2DepartmentofVeterinaryResources,TheWeizmann Institute ofScience, Rehovot,Israel,3DepartmentofPlantSciences,TheWeizmannInstituteofScience,Rehovot,Israel,4DepartmentofHematology,Hadassah-HebrewUniversityMedical Center,Jerusalem,Israel Abstract Background:Antiangiogenicandanti-vasculartherapiespresentintriguingalternativestocancertherapy.However,despite promising preclinical results and significant delays in tumor progression, none have demonstrated long-term curative featurestodate.Here,weshowthatasingletreatmentsessionofTookad-basedvasculartargetedphotodynamictherapy (VTP)promotespermanentarrestoftumorbloodsupplybyrapidocclusionofthetumorfeedingarteries(FA)anddraining veins(DV),leadingtotumornecrosisanderadicationwithin24–48h. Methodology/PrincipalFindings:AmouseearlobeMADB106tumormodelwassubjectedtoTookad-VTPandmonitored by three complementary, non-invasive online imaging techniques: Fluorescent intravital microscopy, Dynamic Light ScatteringImagingandphotosensitizedMRI.Tookad-VTPledtoprompttumorFAvasodilatation(ameanvolumeincrease of 70%) with a transient increase (60%) in blood-flow rate. Rapid vasoconstriction, simultaneous blood clotting, vessel permeabilizationandasharpdeclineintheflowratesthenfollowed,culminatinginFAocclusionat63.2sec61.5SEM.This blockagewasdeemedirreversibleafter10minutesofVTPtreatment.AdecreaseinDVbloodflowwasdemonstrated,witha slightlagfromFAresponse,accompaniedbyfrequentchangesinflowdirectionbeforereachingacompletestandstill.In contrast,neighboring,healthytissuevesselsofsimilarsizesremainedintactandfunctionalafterTookad-VTP. Conclusion/Significance: Tookad-VTP selectively targets the tumor feeding and draini