液态氟碳纳米脂质微粒与全氟丙烷纳米脂质微泡的物理特性及体外显影效果比较
액태불탄납미지질미립여전불병완납미지질미포적물리특성급체외현영효과비교
An in vitro comparative study of the physical and imaging enhancement characteristics between two nano-scale ultrasound contrast agents: PFOB lipid particles and C3F8 lipid microbubbles
  • 万方数据
    中华核医学与分子影像杂志 중화핵의학여분자영상잡지
    Chinese Journal of Nuclear Medicine and Molecular Imaging
    2013年 1期 4-9 ,共6页

    刘莹莹%谢明星%徐金锋%王新房%吕清%张丽%覃小娟%项飞翔%张艳容

    류형형%사명성%서금봉%왕신방%려청%장려%담소연%항비상%장염용

    造影剂%超声检查%纳米脂质微粒%纳米脂质微泡%对比研究 造影劑%超聲檢查%納米脂質微粒%納米脂質微泡%對比研究
    조영제%초성검사%납미지질미립%납미지질미포%대비연구
    Contrast media%Ultrasonography%Lipid nanoparticles%Lipid microbubbles%Comparative study
    目的 制备液态氟碳(PFOB)纳米脂质微粒与全氟丙烷气体(C3F8)纳米脂质微泡,比较两者一般理化性质及体外显影效果.方法 分别制备PFOB纳米脂质微粒与C3F8纳米脂质微泡,检测2种造影剂形态、粒径、表面电位、浓度及稳定性,并进行比较.制备生物素化(外膜标记生物素)及空白(外膜未标记生物素)的PFOB脂质微粒及C3F8微泡造影剂.以高频探头观察各组造影剂加入亲和素前后的显影效果,并运用Matlab软件获得图像平均灰度值,再进行统计分析.2组间比较采用两样本t检验,同一样本多个时间点观察比较采用重复测量方差分析,组内不同时间点间两两比较采用Bonferroni法,同一样本加入亲和素前后的显影强度比较采用配对t检验.结果 (1)PFOB脂质微粒与C3F8脂质微泡粒径分别为(152.30±35.99) nm和(774.59±108.59)nm,前者明显小于后者(t=-24.327,P＜0.001)；表面电位分别为(-40.90±6.51)mV和(-14.80±3.97)mV,前者明显大于后者(t=-15.308,P＜0.001).(2)PFOB脂质微粒造影剂的浓度及粒径在整个观察期间内无明显改变[C0h:(2.28 ±0.64) ×1011/ml,C1周:(2.06 ±0.53)×1011/ml; D0 h:(152.30±35.99) nm,D1周:(178.80±63.07)nm].C3F8脂质微泡造影剂制备后放置12 h,浓度[C0h:(4.08±0.96) ×1010/ml,C12 h:(3.25±1.02)×1010/ml]尚未发生明显改变,而放置24 h、2d、4d及1周后浓度明显减低[C24h:(2.28 ±0.73)×1010/ml,C2d:(1.56±0.54)×1010/ml,C4d:(1.03±0.37) ×1010/ml,C1周:(0.74±0.24)×1010/ml;F=78.515,P＜0.01]；C3F8微泡造影剂放置2d内粒径[D0h:(774.59±108.59) nm,D2d:(1020.68 ±223.64) nm]未见明显变化,放置4d及1周后粒径明显增大[D4d:(1391.67 ±268.65) nm,D1周:(1532.41±326.25) nm,F=50.772,P＜0.01].(3)加入亲和素前,空白及生物素化PFOB脂质微粒均未见明显显影,而空白及生物素化C3F8脂质微泡均有较高的显影强度(31.34 ±7.03与28.75±7.18)；加入亲和素之后,生物素化PFOB脂质微粒造影剂显影明显增强(2.18 ±0.71和82.19±15.68,t=-15.698,P＜0.001),而空白PFOB脂质微粒及2组脂质C3F8微泡显影情况无明显改变.结论 与C3F8脂质微泡造影剂相比,以PFOB为核心的纳米脂质微粒造影剂在粒径优化和稳定性方面具有更好的可控性,且具有独特的显影特性,有利于制备靶向功能的超声造影剂.
    목적 제비액태불탄(PFOB)납미지질미립여전불병완기체(C3F8)납미지질미포,비교량자일반이화성질급체외현영효과.방법 분별제비PFOB납미지질미립여C3F8납미지질미포,검측2충조영제형태、립경、표면전위、농도급은정성,병진행비교.제비생물소화(외막표기생물소)급공백(외막미표기생물소)적PFOB지질미립급C3F8미포조영제.이고빈탐두관찰각조조영제가입친화소전후적현영효과,병운용Matlab연건획득도상평균회도치,재진행통계분석.2조간비교채용량양본t검험,동일양본다개시간점관찰비교채용중복측량방차분석,조내불동시간점간량량비교채용Bonferroni법,동일양본가입친화소전후적현영강도비교채용배대t검험.결과 (1)PFOB지질미립여C3F8지질미포립경분별위(152.30±35.99) nm화(774.59±108.59)nm,전자명현소우후자(t=-24.327,P＜0.001)；표면전위분별위(-40.90±6.51)mV화(-14.80±3.97)mV,전자명현대우후자(t=-15.308,P＜0.001).(2)PFOB지질미립조영제적농도급립경재정개관찰기간내무명현개변[C0h:(2.28 ±0.64) ×1011/ml,C1주:(2.06 ±0.53)×1011/ml; D0 h:(152.30±35.99) nm,D1주:(178.80±63.07)nm].C3F8지질미포조영제제비후방치12 h,농도[C0h:(4.08±0.96) ×1010/ml,C12 h:(3.25±1.02)×1010/ml]상미발생명현개변,이방치24 h、2d、4d급1주후농도명현감저[C24h:(2.28 ±0.73)×1010/ml,C2d:(1.56±0.54)×1010/ml,C4d:(1.03±0.37) ×1010/ml,C1주:(0.74±0.24)×1010/ml;F=78.515,P＜0.01]；C3F8미포조영제방치2d내립경[D0h:(774.59±108.59) nm,D2d:(1020.68 ±223.64) nm]미견명현변화,방치4d급1주후립경명현증대[D4d:(1391.67 ±268.65) nm,D1주:(1532.41±326.25) nm,F=50.772,P＜0.01].(3)가입친화소전,공백급생물소화PFOB지질미립균미견명현현영,이공백급생물소화C3F8지질미포균유교고적현영강도(31.34 ±7.03여28.75±7.18)；가입친화소지후,생물소화PFOB지질미립조영제현영명현증강(2.18 ±0.71화82.19±15.68,t=-15.698,P＜0.001),이공백PFOB지질미립급2조지질C3F8미포현영정황무명현개변.결론 여C3F8지질미포조영제상비,이PFOB위핵심적납미지질미립조영제재립경우화화은정성방면구유경호적가공성,차구유독특적현영특성,유리우제비파향공능적초성조영제.
    Objective To prepare two nano-scale ultrasound contrast agents,lipid particles and microbubbles,and to compare their physical and imaging enhancement characteristics.Methods Lipid nanoparticles were prepared with phospholipid and liquid perfluorocarbon (PFOB).Lipid microbubbles were prepared with phospholipid and perfluoropropane(C3F8).Physical and chemical properties of the two ultrasound contrast agents were measured,including morphology,size,zeta potential,concentration and stability.Both lipid nanoparticles and microbubbles with/without biotin were imaged using a 12.0 MHz linear-array transducer with/without avidin.The imaging data were analyzed by using Matlab software.Comparative data between the two groups were statistically analyzed by two-sample t test.Repeated measures analysis of variance was used among the observations at multiple time points within the same sample and Bonferroni method was used for post hoc analysis.Comparison of the signal intensity with and without avidin of the same sample was performed by paired t test.Results (1) Microscopically,both PFOB lipid particles and C3F8 microbubbles were in form of spheres.Their particle diameters were (152.30 ± 35.99) nm and (774.59 ± 108.59) nm,respectively (t =-24.327,P ＜ 0.001).Their zeta potential was (-40.90 ±6.51) mV and (-14.80 ± 3.97) mV,respectively (t =-15.308,P ＜ 0.001).(2) Concentration and size of PFOB lipid particles remained stable during the whole observation period (C0h =(2.28 ± 0.64) ×1011/ml,C1w =(2.06 ±0.53) × 1011/ml; D0h =(152.30 ±35.99) nm,D1 w =(178.80 ±63.07) nm).Concentrations of lipid microbubbles were stable within 12 h (C0h =(4.08 ± 0.96) × 1010/ml,C12h =(3.25 ± 1.02) × 1010/ml) ; and then reduced significantly after 24 h,2 d,4 d and 1 week (C24h:(2.28 ±0.73) ×1010/ml; C2d:(1.56±0.54) ×1010/ml; C4d:(1.03±0.37) ×1010/ml; C1w:(0.74 ±0.24) ×1010/ml ; F =78.515,P ＜ 0.01).Diameters of the particles remained stable within 2 d (D0h =(774.59 ±108.59) nm,D2d =(1020.68 ± 223.64) nm) ; and then increased after 4 d and 1 week (D4d:(1391.67 ±268.65) nm; D1w:(1532.41 ± 326.25) nm,respectively,F =50.772,P ＜ 0.01).(3) Neither control nor biotinylated PFOB particles were visible without avidin.With the addition of avidin,significantly enhanced images were generated by biotinylated PFOB particles (2.18 ±0.71,82.19 ± 15.68,t =-15.698,P ＜ 0.001) but not with the control PFOB particles.Both control and biotinylated C3F8 microbubbles showed no significant difference in their signal intensity with/without avidin (29.16 ± 6.84 and 31.34 ±7.03,33.69±8.24 and28.75±7.18,t=0.653,-1.393,bothP＞0.05).Conclusion Compared to C3F8 microbubbles,PFOB particles have smaller size,greater stability,higher SNR ratio and better imaging enhancement characteristics,therefore,more suitable for use as the target contrast agent for ultrasound imaging.
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