HepaSphere栓塞微球临床应用及病例分享

HepaSphere栓塞微球临床应用及病例分享1990:由日本教授Hori发明，名称：SAP*1992:首次应用于临床2000:应用于HCC的初步研究2004:获得欧盟认证，名称：HepaSphere2006:获得美国认证，名称：QuadraSphere历史*SAP：SuperabsorbentPolymerMicrosphereHepaSphere的材质乙酸乙烯和丙烯酸甲酯经聚合皂化反应生成的共聚物聚丙烯酸钠乙烯醇(polyvinylalcohol-co-acrylicacid)•HepaSphere栓塞微球–干态包装，每瓶25mg–500-100um粒径，139,000微粒/瓶–30-60um粒径，815,000微粒/瓶HepaSphere的粒径小粒径微球才更有可能实现末梢栓塞，效果才会更好可压缩直径的80%•良好的弹性，撤掉外力即可恢复原来的形状•可变形，能复原—像棉花糖一样HepaSphere的物理性能TACE•精准的靶向性（Targeted）•良好的吸收性（Absorbing）•高度的随形性（Conforming）•真正的载药性（Eluting）HepaSphere的特性•HepaSphere微球粒径分布均一–50-100um粒径HepaSphere微球，95%在40-110um区间内–粒径均匀，更易完成指定层面栓塞GuidoPoggietal.Transhepaticarterialchemoembolizationwithoxaliplatin-elutingmicrospheres(OEM-TACE)forunresectablehepatictumors,AnticancerRes.2008Nov-Dec;28(6B):3835-42精准的靶向性（Targeted）•HepaSphere不会在血管近端或者远端发生聚集•在体内栓塞的血管直径与其粒径大小一致1.KhankanAA,OsugaK,HoriSetal.Emboliceffectsofsuperabsorbentpolymermicrospheresinrabbitrenalmodel:comparisonwithtris-acrylgelatinmicrospheresandpolyvinylalcohol.RadiatMed22:384–3902.BilbaoJl,DeLuisE,GarciaDeJalonJAetal.Comparativestudyoffourdifferentsphericalembolicparticlesinananimalmodel:amorphologicandhistologicevaluation.JVascIntervRadiol.2008Nov;19(11):1625-38精准的靶向性（Targeted）•注射前需要水合•水合时产品能较好吸收水基溶液，吸收部分药液•吸收后以球形方式膨胀，直径为原来的2-4倍良好的吸收性（Absorbing）干态离子型造影剂血液，0.9%NaCl，非离子型造影剂直径（D）D2xD4xD体积（V）V=1/6πD38xV64xV良好的吸收性（Absorbing）•Hepa膨胀的大小受控于水基溶液的离子浓度•HepaSphere可以像血管腔的模子一样堵在血管腔内，形成完全的栓塞•HepaSphere与血管腔高度随形，在血管内不断裂，也不移位，平均每个血管腔内一个颗粒•HepaSphere很软，容易压缩，所以能够适合管腔的形状并实现完全堵塞1.KhankanAA,OsugaK,HoriSetal.Emboliceffectsofsuperabsorbentpolymermicrospheresinrabbitrenalmodel:comparisonwithtris-acrylgelatinmicrospheresandpolyvinylalcohol.RadiatMed22:384–3902.BilbaoJl,DeLuisE,GarciaDeJalonJAetal.Comparativestudyoffourdifferentsphericalembolicparticlesinananimalmodel:amorphologicandhistologicevaluation.JVascIntervRadiol.2008Nov;19(11):1625-38高度的随形性（Conforming）在人体组织上得到的证实：与血管内皮紧密接触并随形，从而达到完全性栓塞的效果Klassetal2014.ANTICANCERRESEARCH34:3597-3606(2014)高度的随形性（Conforming）Bilbaoetal.“ComparativeStudyofFourDifferentSphericalEmbolicParticlesinanAnimalModel:AMorphologicandHistologicEvaluation.”JVascIntervRadiol2008;19(11):1625-38.载药微球与肿瘤血管内皮接触越紧密，抗癌药物缓释到肿瘤内部的效果越好PhotoscourtesyofKeigoOsuga高度的随形性（Conforming）•机械吸收–HepaSphere由干燥的颗粒变成水合微球–约在10分钟内完成•正负电荷结合–HepaSphere微球带负电荷的丙烯酸酯与带正电荷的盐酸多柔比星之间形成离子键11.KosSetal.,Elutioncharacteristicsofdoxorubicin-loadedmicrospheresdifferbydrug-loadingmethodandmicrospheresize,JVascIntervRadiol.2011Mar;22(3):361-8真正的载药性（Eluting）HepaSphere为整体载药1，21.SebastianKosetal.ElutionCharacteristicsofDoxorubicin-loadedMicrospheresDifferbyDrug-loadingMethodandMicrosphereSize,JvascIntervradiol2011;22:361-3682.DavidM.Liuetal.OptimizationofDoxorubicinLoadingforSuperabsorbentPolymerMicrospheres:invitroAnalysis,CardiovascInterventRadiol(2012)35:391-398真正的载药性（Eluting）•HepaSphere可加载多种药物：–多柔比星1–顺铂2,3,4–伊立替康5–奥沙利铂61.KosSetal.Elutioncharacteristicsofdoxorubicin-loadedmicrospheresdifferbydrug-loadingmethodandmicrospheresize,JVascIntervRadiol.2011Mar;22(3):361-82.MaedaNetal.,Invivoevaluationofcisplatin-loadedsuperabsorbentpolymermicrospheresforuseinchemoembolizationofVX2livertumors,JVascIntervRadiol.2012Mar;23:397-4043.MaedaNetal.,Invitrocharacterizationofcisplatin-loadedsuperabsorbentpolymermicrospheresdesignedforchemoembolization,JVascIntervRadiol.2010;21(6):877–814.HuppertP,TranscatheterArterialChemoembolization(TACE)ofColorectalCancerLiverMetastasesbyIrinotecan-ElutingMicrospheresinaSalvagePatientPopulation,CardiovascInterventRadiol.2013May;37(1):154-1645.PoggiG,Transhepaticarterialchemoembolizationwithoxaliplatin-elutingmicrospheres(OEM-TACE)forunresectablehepatictumors,AnticancerRes.2008Nov-Dec;28(6B):3835-426.PoggiG,Oxaliplatin-elutingmicrospheresforthetreatmentofintrahepaticcholangiocarcinoma:acasereport,AnticancerRes.2008Sep-Oct;28(5B):2987-90真正的载药性（Eluting）HepaSphere的载药时间Meritbrochure•50-100μmHepaSphere:15分钟加载95%以上的多柔比星•按照麦瑞通推荐的载药方法可以达到这种载药效果KosSetal.Elutioncharacteristicsofdoxorubicin-loadedmicrospheresdifferbydrug-loadingmethodandmicrospheresize,JVascIntervRadiol.2011Mar;22(3):361-8HepaSphere的载药时间•3组VX2兔模型，分别为HepaSphere加载阿霉素，碘油+阿霉素+Embo栓塞的cTACE，以及经肝动脉灌注阿霉素（HAI）•Hepa组14天后局部药物浓度仍可以达到治疗效果Guptaetal.“HepaticArterialEmbolizationwithDoxorubicin-LoadedSuperabsorbentPolymerMicrospheresinaRabbitLiverTumorModel.”CardiovascInterventRadiol2011;34(5):1021-30Hepa组：14天肿瘤内部药物浓度大于50ng/mgcTACE组：第3天已经接近为0HepaSphere的药代动力学特性术后第1天术后第3天术后第7天术后第14天将加载多柔比星的HepaSphere注入兔VX2肝肿瘤模型中，荧光成像证明术后1、3、7、14天均可探测到多柔比星渗透到周围组织中（多柔比星呈红色荧光）。Guptaetal.“HepaticArterialEmbolizationwithDoxorubicin-LoadedSuperabsorbentPolymerMicrospheresinaRabbitLiverTumorModel.”CardiovascInterventRadiol2011;34(5):1021-30.HepaSphere的药代动力学特性•HepaSphere能够有效加载多柔比星•HepaSphere做到了持续释放，在各时间点均可提高肿瘤内多柔比星的浓度Leeetal.“Doxorubicin-LoadedQuadraSphereMicrospheres:PlasmaPharmacokineticsandIntratumoralDrugConcentrationinanAnimalModelofLiverCancer.”CardiovascInterventRadiol2010;33(3):576–82.HepaSphere的药代动力学特性Hepa提高了肿瘤局部的药物浓度•术后第7天HepaSphere载药组肿瘤坏死率为90%，而空白栓塞组为60%•HepaSphere载药组的肿瘤坏死率明显高于空白栓塞组Leeetal.“Doxorubicin-LoadedQuadraSphereMicr