中华核医学与分子影像杂志
中華覈醫學與分子影像雜誌
중화핵의학여분자영상잡지
Chinese Journal of Nuclear Medicine and Molecular Imaging
2012年
6期
457-462
,共6页
孙柳静%邵国强%王自正%朱喜山%徐龙宝%赵骏
孫柳靜%邵國彊%王自正%硃喜山%徐龍寶%趙駿
손류정%소국강%왕자정%주희산%서룡보%조준
前列腺肿瘤%肿瘤移植%近距离放射疗法%磷放射性同位素%磷酸铬-聚L-乳酸%小鼠,裸
前列腺腫瘤%腫瘤移植%近距離放射療法%燐放射性同位素%燐痠鉻-聚L-乳痠%小鼠,裸
전렬선종류%종류이식%근거리방사요법%린방사성동위소%린산락-취L-유산%소서,라
Prostatic neoplasms%Neoplasm transplantation%Brachytherapy%Phosphorus radioisotopes%Chromic phosphate-poly (L-lactide)%Mice,nude
目的 观察32P-磷酸铬-聚L-乳酸(CP-PLLA)粒子瘤体植入后对荷人前列腺癌裸鼠移植瘤的抑瘤效应和体内药物分布.方法 采用雄性BALB/c裸小鼠建立人前列腺癌PC-3M细胞株的裸鼠皮下移植瘤模型,按随机数字表法分为4组,每组8只,即空白对照组和低、中、高剂量组(各植入3.7、7.4和18.5 MBq粒子1枚).植入后第2天每组各处死3只小鼠,取瘤体标本,采用原位末端标记法(TUNEL)观察肿瘤细胞凋亡并计算凋亡率.另5只裸鼠每2天测量肿瘤体积.植入后1h、2h、1d、2d、4d和8d对裸鼠行放射性核素显像,观察32P-CP-PLLA粒子的放射性动态分布.植入后第14天处死小鼠,测量瘤体放射性活度和质量,计算放射性滞留率和抑瘤率,行常规病理检查观察瘤体和主要脏器病理变化,计算瘤细胞坏死率.免疫组织化学法检测肿瘤微血管密度(MVD)的表达.抑瘤率、瘤细胞坏死率和MVD组间差异采用单因素方差分析和SNK-q检验.结果 放射性核素显像示放射性高度浓聚在植入靶位,并且瘤内弥散.粒子植入后第14天,各活度组肿瘤体积差异有统计学意义(F=212.820,P＜0.01)；瘤体病理示坏死性改变,TUNEL检测示肿瘤细胞大量凋亡,凋亡率[第2天分别为(1.66±0.56)％、(34.51±6.68)％、(42.45±6.09)％和(57.01±3.13)％]、瘤细胞坏死率[(4.86±4.12)％、(65.43±8.06)％、(76.18±6.35)％、(85.85±3.05)％]和抑瘤率[(60.82±3.81)％、(73.17±4.55)％、(81.80±4.74)％]均随给药剂量增加而同步增高.低、中和高剂量组瘤体放射性滞留率分别为(34.36±5.78)％、(41.16±5.26)％和(44.70±3.83)％(F=6.311,P＜0.05)；空白对照组、低、中和高剂量组MVD分别为62.00 ±5.40、38.16±4.16、23.50±4.59和15.80 ±3.92(q=14.31、23.11、27.74、8.80、13.43和4.62,均P＜0.01).肝、脾等主要脏器未见明显病理学异常.结论 32P-CP-PLLA粒子植入后靶向浓聚,持续释放,具有杀伤、诱导凋亡和抑制肿瘤血管生成作用,且抑瘤效应和瘤内药物滞留率均存在一定的剂量-效应关系.
目的 觀察32P-燐痠鉻-聚L-乳痠(CP-PLLA)粒子瘤體植入後對荷人前列腺癌裸鼠移植瘤的抑瘤效應和體內藥物分佈.方法 採用雄性BALB/c裸小鼠建立人前列腺癌PC-3M細胞株的裸鼠皮下移植瘤模型,按隨機數字錶法分為4組,每組8隻,即空白對照組和低、中、高劑量組(各植入3.7、7.4和18.5 MBq粒子1枚).植入後第2天每組各處死3隻小鼠,取瘤體標本,採用原位末耑標記法(TUNEL)觀察腫瘤細胞凋亡併計算凋亡率.另5隻裸鼠每2天測量腫瘤體積.植入後1h、2h、1d、2d、4d和8d對裸鼠行放射性覈素顯像,觀察32P-CP-PLLA粒子的放射性動態分佈.植入後第14天處死小鼠,測量瘤體放射性活度和質量,計算放射性滯留率和抑瘤率,行常規病理檢查觀察瘤體和主要髒器病理變化,計算瘤細胞壞死率.免疫組織化學法檢測腫瘤微血管密度(MVD)的錶達.抑瘤率、瘤細胞壞死率和MVD組間差異採用單因素方差分析和SNK-q檢驗.結果 放射性覈素顯像示放射性高度濃聚在植入靶位,併且瘤內瀰散.粒子植入後第14天,各活度組腫瘤體積差異有統計學意義(F=212.820,P＜0.01)；瘤體病理示壞死性改變,TUNEL檢測示腫瘤細胞大量凋亡,凋亡率[第2天分彆為(1.66±0.56)％、(34.51±6.68)％、(42.45±6.09)％和(57.01±3.13)％]、瘤細胞壞死率[(4.86±4.12)％、(65.43±8.06)％、(76.18±6.35)％、(85.85±3.05)％]和抑瘤率[(60.82±3.81)％、(73.17±4.55)％、(81.80±4.74)％]均隨給藥劑量增加而同步增高.低、中和高劑量組瘤體放射性滯留率分彆為(34.36±5.78)％、(41.16±5.26)％和(44.70±3.83)％(F=6.311,P＜0.05)；空白對照組、低、中和高劑量組MVD分彆為62.00 ±5.40、38.16±4.16、23.50±4.59和15.80 ±3.92(q=14.31、23.11、27.74、8.80、13.43和4.62,均P＜0.01).肝、脾等主要髒器未見明顯病理學異常.結論 32P-CP-PLLA粒子植入後靶嚮濃聚,持續釋放,具有殺傷、誘導凋亡和抑製腫瘤血管生成作用,且抑瘤效應和瘤內藥物滯留率均存在一定的劑量-效應關繫.
목적 관찰32P-린산락-취L-유산(CP-PLLA)입자류체식입후대하인전렬선암라서이식류적억류효응화체내약물분포.방법 채용웅성BALB/c라소서건립인전렬선암PC-3M세포주적라서피하이식류모형,안수궤수자표법분위4조,매조8지,즉공백대조조화저、중、고제량조(각식입3.7、7.4화18.5 MBq입자1매).식입후제2천매조각처사3지소서,취류체표본,채용원위말단표기법(TUNEL)관찰종류세포조망병계산조망솔.령5지라서매2천측량종류체적.식입후1h、2h、1d、2d、4d화8d대라서행방사성핵소현상,관찰32P-CP-PLLA입자적방사성동태분포.식입후제14천처사소서,측량류체방사성활도화질량,계산방사성체류솔화억류솔,행상규병리검사관찰류체화주요장기병리변화,계산류세포배사솔.면역조직화학법검측종류미혈관밀도(MVD)적표체.억류솔、류세포배사솔화MVD조간차이채용단인소방차분석화SNK-q검험.결과 방사성핵소현상시방사성고도농취재식입파위,병차류내미산.입자식입후제14천,각활도조종류체적차이유통계학의의(F=212.820,P＜0.01)；류체병리시배사성개변,TUNEL검측시종류세포대량조망,조망솔[제2천분별위(1.66±0.56)％、(34.51±6.68)％、(42.45±6.09)％화(57.01±3.13)％]、류세포배사솔[(4.86±4.12)％、(65.43±8.06)％、(76.18±6.35)％、(85.85±3.05)％]화억류솔[(60.82±3.81)％、(73.17±4.55)％、(81.80±4.74)％]균수급약제량증가이동보증고.저、중화고제량조류체방사성체류솔분별위(34.36±5.78)％、(41.16±5.26)％화(44.70±3.83)％(F=6.311,P＜0.05)；공백대조조、저、중화고제량조MVD분별위62.00 ±5.40、38.16±4.16、23.50±4.59화15.80 ±3.92(q=14.31、23.11、27.74、8.80、13.43화4.62,균P＜0.01).간、비등주요장기미견명현병이학이상.결론 32P-CP-PLLA입자식입후파향농취,지속석방,구유살상、유도조망화억제종류혈관생성작용,차억류효응화류내약물체류솔균존재일정적제량-효응관계.
Objective To investigate the anti-tumor effects and distribution of 32P-chromic-phosphate poly(L-lactide)(CP-PLLA) in nude mice bearing the prostate cancer cell line PC-3M.Methods Tumor xenograft models were established with PC-3M prostate cancer cell line in male BALB/c nude mice.Based on the implanted dosage of 32P-CP-PLLA particles,the mice were randomly divided into four groups:control group (n =8,0 MBq),low-dose group (n =8,3.7 MBq),middle-dose group (n =8,7.4 MBq) and high-dose group (n =8,18.5 MBq).Three mice from each group were sacrificed 2 d after the 32P-CPPLLA particles were implanted into the tumor.Cell apoptosis was analyzed by a terminal oxynucleotidyl transferase mediated dUTP biotin nick and labeling (TUNEL) method,upon which the apoptotic rate was calculated.Tumor volume was measured every two days.The in vivo distribution of 32P-CP-PLLA was observed by SPECT.Mice in each group (n =5) were sacrificed on the 14th day.The weight and radioactivity of tumors were measured,so that the radioactive retention ratio and tumor growth inhibition rate could be calculated.The pathological changes of tumors and livers were observed,allowing the tumor necrotic rate to be calculated.The intratumoral microvessel density (MVD) was evaluated by an immunohistochemical method.Statistical analysis was performed by one-way analysis of variance and SNK-q analysis.Results 32P mainly accumulated in the tumor.Significant differences were noted in the tumor volumes among all groups on the 14th day (F =212.820,P ＜ 0.01).Massive tumor necrosis was observed by pathologic examination.After exposure to 0,3.7,7.4 and 18.5 MBq 32P-CP-PLLA,the apoptotic rates of tumors on the 2nd day were (1.66 ±0.56)％,(34.51 ±6.68)％,(42.45 ±6.09)％ and (57.01 ±3.13)％,respectively.On the 14th day,the tumor necrotic rates were (4.86 ±4.12)％,(65.43 ±8.06)％,(76.18 ±6.35)％ and (85.85 ±3.05)％,respectively and the tumor growth inhibition rates were (60.82 ± 3.81) ％,(73.17 ± 4.55) ％,(8 1.80 ± 4.74) ％,respectively.The apoptotic rate,tumor necrotic rate and tumor growth inhibition rate all showed a dose-effect relationship.When the dose was 3.7,7.4 and 18.5 MBq,the radioactive retention ratios in the tumors were (34.36 ±5.78)％,(41.16 ±5.26) ％ and (44.70 ± 3.83) ％,respectively (F =6.311,P ＜ 0.05).When the dose was 0,3.7,7.4 and 18.5 MBq,the MVD was 62.00 ±5.40,38.16 ±4.16,23.50 ±4.59 and 15.80 ±3.92,respectively (F=128.613,q=14.31,23.11,27.74,8.80,13.43,4.62,all P＜0.01).No pathological changes were observed in the liver or spleen.Conclusions The 32P-CP-PLLA particles released in the tumor and accumulated significantly at the implantation site.It shows apparent antitumor effects,including inducing apoptosis and inhibiting angiogenesis.In addition,a dose-effect relationship is noted between the antitumor effects and radioactive retention ratios of the tumors.
