中华放射学杂志
中華放射學雜誌
중화방사학잡지
Chinese Journal of Radiology
2014年
5期
369-374
,共6页
康晓伟%乔瑞瑞%梁树辉%吴开春%刘先平%印弘%高明远%魏光全
康曉偉%喬瑞瑞%樑樹輝%吳開春%劉先平%印弘%高明遠%魏光全
강효위%교서서%량수휘%오개춘%류선평%인홍%고명원%위광전
胃肿瘤%分子探针%磁共振成像
胃腫瘤%分子探針%磁共振成像
위종류%분자탐침%자공진성상
Stomach neoplasms%Molecular probes%Magnetic resonance imaging
目的：构建靶向胃癌新生血管的特异性MR光学双模态分子探针，并初步研究其物理特征、体外细胞毒性及不同脉冲序列的磁化效应。方法将荧光标记的胃癌新生血管靶向性环肽GX1-Cy5.5与表面功能化的磁性纳米颗粒按照不同摩尔质量（1∶100、1∶500）共价耦合，获得双模态探针DPs100（简称DPs）和DPs500，测定其水合粒径和Zeta电位，并估算偶联结合率。采用二苯基四氮唑溴盐比色（ MTT）法测定DPs对人脐静脉内皮细胞HUVECs和胃癌细胞BGC823活性率的影响。配置不同浓度DPs溶液行MR扫描，观察在不同扫描序列下的相对信号强度（ΔSI ）。不同浓度（0.00、1.25、2.50、15.00、50.00、100.00和150.00μg/ml） DPs处理HUVECs和BGC-823后测得的A值采用单因素方差分析比较；FSE、快速扰相梯度回波（ FSPGR ）和单次激发快速自旋回波（ SSFSE ）序列间ΔSI的比较采用配对资料Wilcoxon符号秩和检验。结果靶向胃癌新生血管双模态探针构建成功。氧化铁颗粒、DPs100和 DPs500的平均水合粒径分别为（35.23±0.07）、（39.49±0.16）和（40.43±1.70）nm；平均Zeta电位分别为（0.31±0.20）、（-4.15±0.79）和（-10.51±2.37） mV。 DPs100和DPs500探针的多肽偶联率分别为92％和94％。不同浓度DPs对HUVECs细胞的A值分别为0.76±0.04、0.80±0.03、0.79±0.05、0.75±0.06、0.74±0.05、0.77±0.01和0.71±0.04，对BGC823细胞的A值分别为0.38±0.04、0.43±0.04、0.41±0.03、0.43±0.07、0.44±0.04、0.41±0.07和0.40±0.04，差异均无统计学意义（F值分别为0.94、0.51，P值均＞0.05）。 T1WI信号强度随DPs浓度的增加先升高后降低，FSPGR T1WI相对信号强度大于FSE T1WI（Z＝-3.294，P＜0.05）；T2WI信号强度随DPs浓度的增大逐渐增加，当DPs＞10μg/ml时，FSE T2 WI与SSFSE T2倡WI相对信号强度差异无统计学意义（Z＝-7.110，P＞0.05）；当DPs≤10μg/ml时，SSFSE T2倡WI较FSE T2WI信号降低更明显（ Z＝-2.023，P＜0.05）。结论双模态分子探针DPs具有很好的稳定性，SSFSE T倡2 WI序列为检测探针最敏感序列。
目的：構建靶嚮胃癌新生血管的特異性MR光學雙模態分子探針，併初步研究其物理特徵、體外細胞毒性及不同脈遲序列的磁化效應。方法將熒光標記的胃癌新生血管靶嚮性環肽GX1-Cy5.5與錶麵功能化的磁性納米顆粒按照不同摩爾質量（1∶100、1∶500）共價耦閤，穫得雙模態探針DPs100（簡稱DPs）和DPs500，測定其水閤粒徑和Zeta電位，併估算偶聯結閤率。採用二苯基四氮唑溴鹽比色（ MTT）法測定DPs對人臍靜脈內皮細胞HUVECs和胃癌細胞BGC823活性率的影響。配置不同濃度DPs溶液行MR掃描，觀察在不同掃描序列下的相對信號彊度（ΔSI ）。不同濃度（0.00、1.25、2.50、15.00、50.00、100.00和150.00μg/ml） DPs處理HUVECs和BGC-823後測得的A值採用單因素方差分析比較；FSE、快速擾相梯度迴波（ FSPGR ）和單次激髮快速自鏇迴波（ SSFSE ）序列間ΔSI的比較採用配對資料Wilcoxon符號秩和檢驗。結果靶嚮胃癌新生血管雙模態探針構建成功。氧化鐵顆粒、DPs100和 DPs500的平均水閤粒徑分彆為（35.23±0.07）、（39.49±0.16）和（40.43±1.70）nm；平均Zeta電位分彆為（0.31±0.20）、（-4.15±0.79）和（-10.51±2.37） mV。 DPs100和DPs500探針的多肽偶聯率分彆為92％和94％。不同濃度DPs對HUVECs細胞的A值分彆為0.76±0.04、0.80±0.03、0.79±0.05、0.75±0.06、0.74±0.05、0.77±0.01和0.71±0.04，對BGC823細胞的A值分彆為0.38±0.04、0.43±0.04、0.41±0.03、0.43±0.07、0.44±0.04、0.41±0.07和0.40±0.04，差異均無統計學意義（F值分彆為0.94、0.51，P值均＞0.05）。 T1WI信號彊度隨DPs濃度的增加先升高後降低，FSPGR T1WI相對信號彊度大于FSE T1WI（Z＝-3.294，P＜0.05）；T2WI信號彊度隨DPs濃度的增大逐漸增加，噹DPs＞10μg/ml時，FSE T2 WI與SSFSE T2倡WI相對信號彊度差異無統計學意義（Z＝-7.110，P＞0.05）；噹DPs≤10μg/ml時，SSFSE T2倡WI較FSE T2WI信號降低更明顯（ Z＝-2.023，P＜0.05）。結論雙模態分子探針DPs具有很好的穩定性，SSFSE T倡2 WI序列為檢測探針最敏感序列。
목적：구건파향위암신생혈관적특이성MR광학쌍모태분자탐침，병초보연구기물리특정、체외세포독성급불동맥충서렬적자화효응。방법장형광표기적위암신생혈관파향성배태GX1-Cy5.5여표면공능화적자성납미과립안조불동마이질량（1∶100、1∶500）공개우합，획득쌍모태탐침DPs100（간칭DPs）화DPs500，측정기수합립경화Zeta전위，병고산우련결합솔。채용이분기사담서추염비색（ MTT）법측정DPs대인제정맥내피세포HUVECs화위암세포BGC823활성솔적영향。배치불동농도DPs용액행MR소묘，관찰재불동소묘서렬하적상대신호강도（ΔSI ）。불동농도（0.00、1.25、2.50、15.00、50.00、100.00화150.00μg/ml） DPs처리HUVECs화BGC-823후측득적A치채용단인소방차분석비교；FSE、쾌속우상제도회파（ FSPGR ）화단차격발쾌속자선회파（ SSFSE ）서렬간ΔSI적비교채용배대자료Wilcoxon부호질화검험。결과파향위암신생혈관쌍모태탐침구건성공。양화철과립、DPs100화 DPs500적평균수합립경분별위（35.23±0.07）、（39.49±0.16）화（40.43±1.70）nm；평균Zeta전위분별위（0.31±0.20）、（-4.15±0.79）화（-10.51±2.37） mV。 DPs100화DPs500탐침적다태우련솔분별위92％화94％。불동농도DPs대HUVECs세포적A치분별위0.76±0.04、0.80±0.03、0.79±0.05、0.75±0.06、0.74±0.05、0.77±0.01화0.71±0.04，대BGC823세포적A치분별위0.38±0.04、0.43±0.04、0.41±0.03、0.43±0.07、0.44±0.04、0.41±0.07화0.40±0.04，차이균무통계학의의（F치분별위0.94、0.51，P치균＞0.05）。 T1WI신호강도수DPs농도적증가선승고후강저，FSPGR T1WI상대신호강도대우FSE T1WI（Z＝-3.294，P＜0.05）；T2WI신호강도수DPs농도적증대축점증가，당DPs＞10μg/ml시，FSE T2 WI여SSFSE T2창WI상대신호강도차이무통계학의의（Z＝-7.110，P＞0.05）；당DPs≤10μg/ml시，SSFSE T2창WI교FSE T2WI신호강저경명현（ Z＝-2.023，P＜0.05）。결론쌍모태분자탐침DPs구유흔호적은정성，SSFSE T창2 WI서렬위검측탐침최민감서렬。
Objective To develop an MR optical dual-modality probe targeting angiogenesis of gastric cancer and to study its physical characteristics , in vitro cytotoxicity and magnetic effects of different pulse sequences on 3 T clinical MR scanner.Methods We conjugated GX1-Cy5.5, a novel gastric cancer neo-vasculature targeted peptide labeled with Cy 5.5, to the surface functionalized magnetic nanoparticles according to different molecular weights (1∶100, 1∶500),resulting in dual-modality probe DPs100 and DPs500 (named DPs).The hydrodynamic size and zeta potential of DPs and DPs 500 were analyzed by nano-ZS.The human umbilical vein endothelial cells (HUVECs) and BGC-823 cells were treated with DPs for 24 h, and methyl thiazol tetrazolium ( MTT) method was used to detect the survival rate of cells.DPs with different concentrations were scanned on different MR sequences , and then the relative signal intensity was observed.The absorbance of HUVECs and BGC823 cells treated with DPs of different concentration (0.00, 1.25, 2.50, 15.00, 50.00, 100.00 and 150.00 μg/ml) were compared with single factor analysis of variance.Relative signal intensity of different MR sequences was compared using a paired Wilcoxon signed-rank test.Results The dual-modality probe targeting angiogenesis of gastric cancer was successfully constructed.The hydrodynamic size of iron oxide nanoparticles , DPs100 and DPs500 was (35.23 ±0.07), (39.49 ±0.16) and (40.43 ±1.70) nm and the Zeta potential was (0.31 ±0.20), ( -4.15 ±0.79) and ( -10.51 ± 2.37) mV.The coupled rates of DPs 100 and DPs500 with polypeptide were 92%and 94% respectively.The absorbance of HUVECs and BGC823 cells treated with DPs of different concentrations were 0.76 ±0.04, 0.80 ±0.03, 0.79 ±0.05, 0.75 ±0.06, 0.74 ±0.05, 0.77 ±0.01,0.71 ±0.04 and 0.38 ±0.04, 0.43 ±0.04, 0.41 ±0.03, 0.43 ±0.07, 0.44 ±0.04, 0.41 ±0.07 and 0.40 ±0.04, there was no statistical significance ( F=0.94, 0.51;P>0.05).The signal intensity increased first and then decreased following the increasing concentrations of DPs on T 1WI,especially on FSPGR T1WI (Z =-3.294,P <0.05), while the signal intensity decreased on T2WI or T2*WI.There was no significant differences in signal intensity on FSE T2 WI and SSFSE T2*WI with iron concentration >10μg/ml( Z=-7.110,P>0.05).With iron concentration≤10 μg/ml,the signal intensity on SSFSE T 2*WI was significantly decreased compared to FSE T2 WI ( Z =-2.023, P <0.05 ) .Conclusions DPs may be potential dual-modal probes for characterization of tumor angiogenesis by MR and optical imaging noninvasively , without causing significant effects on the cell activity in vitro , and SSFSE T2*WI may be the most sensitive sequence for DPs evaluation on MR.
