1、顧晗：AFP抗體標(biāo)記USPIO在大鼠肝癌中的MRI顯像及分布變化的實(shí)驗(yàn)研究AFP抗體標(biāo)記USPIO在SD大鼠肝癌中MRI顯像及分布變化的實(shí)驗(yàn)研究中文摘要在我國(guó)肝細(xì)胞癌(Hepatocellular，HCC)的發(fā)病率居全球首位，其死亡率居惡性腫瘤死亡的第二位。肝癌的早期發(fā)現(xiàn)、早期診斷決定著其臨床治療的效果及患者預(yù)后。臨床常用的檢測(cè)手段包括血清AFP檢測(cè)和各種影像學(xué)手段。甲胎蛋白(Alphafetoprotein，AFP)是HCC特異性標(biāo)志

2、物，80％的患者可出現(xiàn)甲胎蛋白的升高。如果將抗AFP抗體與某些顯影劑或(和)抗癌藥物相連，可以實(shí)現(xiàn)對(duì)肝癌的靶向成像和靶向治療，使得影像診斷和臨床治療的同時(shí)進(jìn)行成為可能。本實(shí)驗(yàn)擬通過(guò)對(duì)小劑量二乙基亞硝胺(DENA)誘導(dǎo)SD大鼠原位肝癌模型的MR分子成像、動(dòng)態(tài)觀察和病理學(xué)對(duì)照，研究靶向AFP的超小型超順磁性納米?！釉贖CC中的特異性靶向成像和分布規(guī)律，本研究主要包括兩部分。第一部分：SD大鼠肝癌模型的建立及靶向AFPUSPIO在SD大鼠肝

3、癌中的MR成像表現(xiàn)目的：建立SD大鼠肝癌模型，進(jìn)行AFP抗體標(biāo)記USPIO增強(qiáng)掃描，觀察大鼠肝癌特異性MRI成像。方法：定期配制濃度為01mg／ml的DENA水溶液，予25只雄性SD大鼠自由飲用，喂養(yǎng)14周后改為空白飲用水。16～18周時(shí)選取利于實(shí)驗(yàn)觀察的大鼠肝癌模型20只，完全隨機(jī)分成2組：實(shí)驗(yàn)組10只，對(duì)照組10只。所有大鼠先行MRIT2WI平掃，實(shí)驗(yàn)組注入AFPUSPIO(靶向組)，對(duì)照組注入U(xiǎn)SPIO(非靶向組)2h后行T2WI

4、增強(qiáng)掃描，觀察病灶的信號(hào)變化情況，測(cè)量增強(qiáng)前后病灶、肝臟的信號(hào)強(qiáng)度，計(jì)算其對(duì)比噪聲比(CNR)；處死大鼠后，取病灶標(biāo)本行HE、AFP免疫組化染色和普魯士藍(lán)染色分析。結(jié)果：MRI掃描T2WI示肝內(nèi)多發(fā)大小不等的高、稍高信號(hào)及混雜信號(hào)結(jié)節(jié)影，選取直徑3mm的結(jié)節(jié)作為實(shí)驗(yàn)對(duì)象進(jìn)行觀察。病灶境界顯示清楚，大部分信號(hào)均勻，呈高、稍高信號(hào)。實(shí)驗(yàn)組、對(duì)照組分別注入AFPUSPIO、USPIO后2h增強(qiáng)掃描，在注射AFPUSPIO前后，大鼠肝臟腫瘤的C

5、NR分別為100a：245和473士251，差異有統(tǒng)計(jì)學(xué)意義(PO001，t=1123)；而注射USPIO前后肝臟一腫瘤的CNR分別為915124和996M63，差異無(wú)統(tǒng)顧晗：AFP抗體標(biāo)記USPIO在大鼠肝癌中的MRI顯像及分布變化的實(shí)驗(yàn)研究ExperimentalresearchofAFPantibodylabelingsuperparamagneticironoxidenanoparticlestheMRI’Lgingandits

6、tistribu‘‘onchang。SDratlivercancerlmaglnanitsdistrintiOnchangeinDratercancerAbstractHepatocellularcarcinoma(HCC)isthemostcommonprimarylivercancerthemortalityofHCCisthesecondplaceofallcancersinourcountryTheeffectoftheclin

7、icaltreatmentandprognosisofpatientsdependsonearlydetection，earlydiagnosisClinicalcommonlyuseddetectionmethodsincludingserumAFPandvariousimagingtestsAlphafetoprotein(AFP)isatypicaltumorspecificmarkerfortheHCC，henceitCanbe

8、usedasanefficientandspecificima西ngtargetIftheantiAFPantibodywithsomecontrastagentsor(and)cancerdrugsarelinkedtogetherwecanachievetargetimagingandtargetedtherapyoflivercancerwhichmakestheimagingdiagnosisahdclinicaltreatme

9、ntatthesametimeforpossibleThisexperimentintendedtoconstructAFPtargetedultrasmallsuperparamagneticnanoparticlesThroughcomparingMRimagingtohistopathologyresultonSDratslivercancermodelwhichisinducedbysmalldosesofdiethylnitr

10、osamine，thetargetedimaginganddistributionofAFPtargetednanoparticlesinHCCwerestudiedThisstudymainlyincludestwopartsThefirstpart：EstablishingSDratslivercancermodelandAFPUSPIOtargetedMRimagingperformancesObjective：Toestabli

11、shratslivercancermodel，enhancementscanwithUSPIOmarkedbyAFPantibodyascontrastagentswasconducted，andthehepatomaspecificMRIimagingofratswasobservedMethods：TheO1mgCmlDENAaqueoussolutionwasregularlyformulatedfor25maleSDratsto

12、drinkfreelyfor14weeks，afterwards，theratswerefedwithpuredrinkingwaterinsteadofDENAsolutionInthe16th18thweek，20rathepatomamodelswhichwerebeneficialtoexperimentalobservationwereselectedanddividedintotwogroupscompletelyandra