131I标记抗表皮生长因子受体抗体靶向性纳米载体治疗胶质母细胞瘤的可行性实验研究

目的 构建¹³¹I标记抗表皮生长因子受体抗体(antiEGFR)靶向性的纳米载体,探讨其在细胞水平和动物体内用于胶质瘤治疗的可行性。方法 制备放射性碘(¹³¹I)标记的antiEGFR靶向性的纳米载体牛血清白蛋白聚己内酯复合物¹³¹I-antiEGFR-BSA-PCL。用共聚焦显微镜观察纳米载体能够与肿瘤细胞结合情况,用MTT法检测纳米载体的细胞毒性作用,摄碘率实验检测肿瘤细胞对放射性纳米载体的摄取。制备裸鼠种植瘤模型,通过瘤体内注射给药,观察裸鼠种植瘤的体积变化,通过SPECT显像观察药物在裸鼠体内的停留情况,并分析纳米载体在裸鼠体内的分布情况。结果 成功地制备了BSA-PCL及antiEGFR-BSA-PCL纳米载体。与BSA-PCL相比,antiEGFR-BSA-PCL更容易与肿瘤细胞结合。当放射性纳米载体的放射性活度达到0.925 MBq时,U251和U87细胞的生长抑制率¹³¹I-antiEGFR-BSA-PCL组均高于¹³¹I-BSA-PCL组(t=2.517、2.821,P<0.05),且均高于同组其他剂量(U251:t=2.148、2.693,P<0.05;U87:t=2.436、2.615,P<0.05)。裸鼠体内实验发现两种纳米载体瘤体内注射后均经过肝脏代谢。¹³¹I-antiEGFR-BSA-PCL组荷瘤裸鼠的种植瘤体积较¹³¹I-BSA-PCL组缩小更多(t=4.115,P<0.05)。结论 ¹³¹I-antiEGFR-BSA-PCL在体内外实验中均能够抑制胶质瘤生长,为胶质瘤的治疗和预后评估提供了一种新方法。     

131I-RGD-BSA-PCL用于非小细胞肺癌荷瘤裸鼠SPECT/CT显像及抑瘤作用

目的 探讨¹³¹I-RGD-BSA-PCL核素纳米载体对非小细胞肺癌荷瘤裸鼠模型SPECT/CT显像效果及其对肿瘤的抑制作用。方法 构建纳米脂质体¹³¹I-RGD-BSA-PCL及¹³¹I-BSA-PCL,通过荧光共聚焦显微镜观察该载体在非小细胞肺癌细胞系H460的靶向性结合及细胞摄取情况;采用氯氨T法标记核素纳米载体;流式细胞术观察核素纳米载体对肿瘤细胞的杀伤作用。构建荷瘤裸鼠模型,研究核素纳米载体在荷瘤裸鼠体内的组织分布、肿瘤体积变化及各组荷瘤裸鼠SPECT/CT断层显像。结果 给药后1和8 h,H460细胞质和细胞核对RGD-BSA-PCL、BSA-PCL两种纳米载体均有明显摄取。Na¹³¹I、¹³¹I-BSA-PCL及¹³¹I-RGD-BSA-PCL对H460细胞的早期凋亡率分别为（33.3±12.5）%、（68.4±8.0）%和（70.5±12.2）%。荷瘤裸鼠体内实验中,给药后24和72 h,肿瘤¹³¹I-RGD-BSA-PCL摄取率均高于¹³¹I-BSA-PCL（t=9.53、5.03,P<0.01）。给药后23 d,¹³¹I-RGD-BSA-PCL肿瘤体积抑制最明显（t=126.44,P<0.01）。SPECT/CT显示,给药后21 d,¹³¹I-RGD-BSA-PCL在肿瘤内信号强度明显强于¹³¹I-BSA-PCL。结论 ¹³¹I标记的纳米脂质体¹³¹I-RGD-BSA-PCL对H460细胞裸鼠移植瘤具有明显的抑瘤作用,且¹³¹I-RGD-BSA-PCL能较长时间停留在肿瘤中。     

放射性125I粒子植入对人肺腺癌裸鼠移植瘤微血管生成的影响

目的 探讨放射性¹²⁵I粒子植入对人肺腺癌裸鼠移植瘤微血管生成的影响及其作用机制。方法 制备人肺腺癌细胞A549裸鼠皮下移植瘤模型24只,采用随机数字表法分为4组,每组6只,0、22.2、29.6 MBq组和对照组。用18 G植入针在各组裸鼠瘤体内分别植入放射活度为0、22.2和29.6 MBq ¹²⁵I粒子,每个移植瘤内植入一枚,对照组不予处理。观察肿瘤生长情况,每4天测量肿瘤大小。30 d后处死裸鼠,绘制肿瘤生长曲线。瘤组织免疫组织化学S-P法检测微血管密度（microvascular density,MVD）,并分别用RT-PCR、Western blot法检测血管内皮生长因子（vascular endothelial growth factor,VEGF）和缺氧诱导因子-1α（hypoxia inducible factor-1α,HIF-1α）的mRNA及蛋白的表达。结果 粒子植入治疗后54 d,22.2、29.6 MBq组移植瘤体积明显小于对照组（q=14.117、17.075,P<0.05）,但0 MBq组与对照组、22.2与29.6 MBq组瘤体积差异均无统计学意义（P>0.05）。CD34阳性染色结果显示,22.2 MBq组的MVD为522±119,29.6 MBq组为491±121,明显低于对照组的922±260（q=4.826、5.197,P<0.05）,但0 MBq组与对照组、22.2 MBq组与29.6 MBq组差异均无统计学意义（P>0.05）。RT-PCR检测表明,22.2 MBq组的VEGF和HIF-1α mRNA相对表达量分别为0.279±0.0659和0.370±0.0857,29.6 MBq组为0.215±0.0620、0.278±0.0651,均低于对照组（q=18.881、17.211和15.376、14.733,P<0.05）,但0 MBq组与对照组、22.2 MBq组与29.6 MBq组之间差异均无统计学意义（P>0.05）。Western blot结果显示,22.2 MBq组与29.6 MBq组瘤组织VEGF和HIF-1α蛋白表达均明显减少,与对照组相比,差异有统计学意义（q=5.848、6.263和6.560、7.576,P<0.05）,但0 MBq组与对照组以及22.2 MBq组与29.6 MBq组差异均无统计学意义（P>0.05）。结论 放射性¹²⁵I粒子植入能有效抑制人肺腺癌裸鼠移植瘤微血管生成。     

153Sm-DTPA-c(CGRRAGGSC)对人MHCC97-H肝癌裸鼠模型的抑瘤作用

目的 探讨¹⁵³Sm-DTPA-c(CGRRAGGSC)对人MHCC97-H肝癌裸鼠模型移植瘤生长的抑制作用.方法 采用间接法合成¹⁵³Sm-DTPA-c(CGRRAGGSC)放射性药物.对8种不同细胞系IL-11受体表达,进行Western blot分析,选择肿瘤接种.20只MHCC97-H皮下荷瘤裸鼠按随机数字表法分为4组(对照组,低、中、高剂量组),每组5只.低、中、高剂量组尾静脉分别注入¹⁵³Sm-DTPA-c(CGRRAGGSC),剂量依序为5.5、11.0和22.0 MBq/0.2 ml,对照组尾静脉注入生理盐水0.2 ml.观察16 d后处死,比较肿瘤的体积,计算抑瘤率;观测标本病理改变;免疫组织化学检测5.5 MBq低剂量组瘤体组织治疗后Ki-67、Bcl-2和IL-11受体表达改变;Western blot检测不同剂量组IL-11受体的变化情况.结果 选择IL-11受体表达最高的MHCC97-H细胞接种.尾静脉内注射¹⁵³Sm-DTPA-c(CGRRAGGSC)后,早期瘤体中央可出现坏死、干瘪、结痂,后期又出现坏死周围瘤组织继续增长.低、中、高剂量组抑瘤率分别为(22.72±2.76)%、(34.65±2.36)%和(85.13±5.78)%(F＝89.32, P<0.05).免疫组织化学显示,对照组及低剂量组瘤内IL-11受体阳性率分别为(84.13±5.71)%和(61.57±5.98)%(t=13.62, P<0.05),低剂量组瘤细胞排列相对疏松,细胞内染色数量明显减少.低剂量组Ki-67、Bcl-2阳性率均较对照组下降(t=20.91、6.68, P<0.05).Western blot结果显示,随抑瘤作用增加,IL-11受体蛋白表达降低.结论 ¹⁵³Sm-DTPA-c(CGRRAGGSC)能够有效抑制人MHCC97-H肝癌裸鼠模型移植瘤的生长,促进IL-11受体表达下调及诱导凋亡作用.     

125I粒子抑制肝癌移植瘤血管形成的实验研究

目的 探讨放射性¹²⁵I粒子对肝癌裸鼠皮下移植瘤微血管形成的影响及其机制。方法 构建人肝癌Huh7细胞裸鼠皮下移植瘤模型,将12只裸鼠用随机数表法分为观察组和对照组,每组6只。观察组移植瘤植入一枚活度为2.96×10⁷Bq粒子,对照组植入一枚活度为0的空粒子。每4天测量1次移植瘤体积,记录肿瘤生长曲线。28 d后取下移植瘤,用免疫组织化学染色法检测CD31评估移植瘤微血管密度（MVD）。用免疫组织化学染色法检测血管内皮生长因子-A（VEGF-A）、缺氧诱导因子1α（HIF-1α）蛋白表达,并做半定量分析。用实时荧光定量聚合酶链反应（RT-PCR）检测VEGF-A、HIF-1α mRNA的表达。结果 观察组移植瘤的生长速度较对照组缓慢,粒子植入后12 d两组肿瘤体积差异有统计学意义（t=3.167,P<0.05）,随着观察时间延长,两组肿瘤体积差距加大,在28 d时两组肿瘤体积分别为（963.61±89.56）mm³和（602.10±75.98）mm³（t=7.122,P<0.05）。两组移植瘤组织中CD31均有表达,观察组的MVD较对照组少,差异有统计学意义（t=6.360,P<0.05）。观察组VEGF-A、HIF-1α mRNA及蛋白的表达水平均低于对照组,差异均有统计学意义（t=10.480、6.414、10.890、12.250,P<0.05）。结论 放射性¹²⁵I粒子通过降低肿瘤微血管密度抑制肝癌移植瘤的生长,其机制可能与VEGF-A、HIF-1α的mRNA及蛋白表达减少有关。     

放射性125I粒子对人肺腺癌细胞株A549裸鼠移植瘤生长抑制及细胞凋亡机制研究

目的 探讨放射性¹²⁵I粒子对人肺腺癌细胞株A549裸鼠移植瘤生长抑制及细胞凋亡机制。方法 体外培养人肺腺癌A549细胞,构建BALA/c裸鼠皮下移植瘤模型,待移植瘤长到（300±50）mm³时,将40只荷瘤小鼠采用随机数表法分成4组,分别为空源粒子组（0 mCi组）、0.6和0.8 mCi（1 Ci=3.7×10¹⁰ Bq）组和空白对照组,每组10只。将放射性活度为0、0.6和0.8 mCi的¹²⁵I粒子分别植入裸鼠移植瘤内,空白对照组不作任何处理。每4天定期测量裸鼠体重,共观察32 d。粒子植入移植瘤32 d后处死裸鼠,称量移植瘤质量,绘制裸鼠体重增长曲线。切取瘤组织采用苏木素-伊红（HE）染色观察肿瘤组织病理学变化;末端脱氧核苷酸转移酶-生物素dUTP切口末端标记法（TUNEL）检测肿瘤细胞凋亡;用免疫组织化学法检测凋亡因子P21、Caspase-9、Survivin、Livin蛋白的表达。结果 各组裸鼠无死亡。在放射性粒子植入的第28和32天,0.6和0.8 mCi组裸鼠体重明显小于空白对照组,差异有统计学意义（q=4.26、9.19、4.11、11.59,P<0.05）。0.6和0.8 mCi组瘤体质量均小于空白对照组（q=5.021、5.692,P<0.05）,抑瘤率依次约为49%和62%,而0 mCi组瘤体重与空白对照组比较,差异无统计学意义（P>0.05）。0.6和0.8 mCi组瘤细胞大量变性坏死,0 mCi组与空白对照组的瘤细胞排列紧密,未见明显坏死。0.6和0.8 mCi组的凋亡指数明显增加,分别为（50.00±2.58）%和（62.33±4.51）%,与空白对照组（27.00±4.69）%比较,差异均有统计学意义（q=14.957、10.918,P<0.05）。P21和Caspase-9蛋白在0.6和0.8 mCi组的表达比空白对照组明显增加,差异有统计学意义（χ²=11.380、24.310、11.380、20.376,P<0.05）。Survivin和Livin蛋白在0.6和0.8 mCi组的表达比空白对照组明显减少（χ²=9.643、23.254、15.429、26.667,P<0.05）。结论 放射性¹²⁵I粒子可以抑制肿瘤细胞的增殖,并可能通过上调P21和Caspase-9表达、下调Survivin和Livin表达促进A549细胞的凋亡。     

分化型甲状腺癌患者口服131I后体内活度变化及剂量水平

目的 研究¹³¹I治疗分化型甲状腺癌（DTC）患者体内放射性活度及外部剂量水平的变化规律，分析二者之间的关系，并估算400 MBq患者剂量当量率的修正因子。方法 研究对象为43例甲状腺全切术后，首次行¹³¹I"清甲"治疗的DTC患者，服药量为1 850~3 700 MBq，平均服药量（2 405±777）MBq。分别于口服¹³¹I后2、6、20、22、24、27、30、44、46、48、54、68及72 h，测定患者的体内剩余放射性活度以及患者前部0.3、1及3 m处的剂量当量率。结果 患者服¹³¹I后的体内剩余放射性活度随时间变化函数为A=A₀（1.033 16e^{-0.062 4t}+0.017 17）。可估算出"清甲"治疗的DTC患者有效半减期为12.19 h，体内放射性活度降至400 MBq仅需26.4~38.9 h。患者服用¹³¹I后距其0.3、1及3 m的标准化剂量当量率随时间变化函数分别为：Ḣ_0.3=127.220 7e^{-0.054 8t}+3.765 71、Ḣ₁=30.225 8e^{-0.064 4t}+0.824 67、Ḣ₃=4.161 9e^{-0.061 5t}+0.167 97。患者服¹³¹I后体内剩余放射性活度与1 m处剂量当量率呈正相关（r=0.982，P<0.05），函数为Ḣ₁=0.025A+1.245。DTC患者体内剩余活度分别为1 000、700和400 MBq时，距患者1 m处对应的剂量当量率分为26.2、18.7和11.2 μSv/h。估算活度为400 MBq的患者0.3、1及3 m处剂量当量率的修正因子分别为0.25、0.49及0.70。结论 服用¹³¹I活度在3 700 MBq以下的DTC患者仅需住院2日便可达到出院标准。当DTC患者体内活度降至400 MBq时，其1 m处的剂量当量率远小于25 μSv/h。单纯利用点源公式估算患者周围剂量当量率会造成高估的情况，因此对于公式估算患者周围辐射水平时使用的修正因子还需进一步研究，使模型估算结果更贴合实际情况。     

Stattic抑制STAT3和HIF-1α途径对食管癌裸鼠移植瘤放射敏感性的影响

目的 探讨Stattic对食管癌ECA109细胞裸鼠移植瘤的放射增敏效果及其可能的作用机制。方法 建立食管癌ECA109细胞裸鼠移植瘤模型;移植瘤平均体积增至约150 mm³时,采用随机数表法将24只裸鼠分为4组,药物+照射组（25 mg/kg Stattic+6 Gy）、单纯药物组（25 mg/kg Stattic）、单纯照射组（6 Gy）、对照组,每组6只。25 d后测量移植瘤体积,计算肿瘤体积抑制率,Western blot法检测移植瘤组织中STAT3、缺氧诱导因子-1α（HIF-1α）及血管内皮生长因子（VEGF）蛋白的表达。结果 药物+照射组裸鼠移植瘤体积为（705.1±75.5）mm³,显著低于单纯照射组（1 113.5±101.4） mm³和单纯药物组（1 696.5±100.6）mm³（t=4.35、14.14,P<0.05）,其抑制率达（66.1±3.2）%。Western blot检测发现,药物+照射组移植瘤组织中pSTAT3、HIF-1α、VEGF蛋白表达水平较单纯照射组明显降低（t=17.07、5.05、3.54,P<0.05）。结论 Stattic对食管癌ECA109细胞裸鼠移植瘤具有放射增敏作用,可能与其抑制pSTAT3、HIF-1α、VEGF途径有关。     

125I粒子和60Co γ射线照射对A549及BEAS-2B细胞生物学效应的影响

目的 探讨¹²⁵I粒子和⁶⁰Co γ射线对非小细胞肺癌(NSCLC)A549细胞和正常支气管上皮BEAS-2B细胞生物学效应的影响。方法 A549、BEAS-2B细胞均行¹²⁵I粒子和⁶⁰Co γ射线不同剂量照射;集落形成实验检测细胞存活分数;流式细胞术检测细胞周期和细胞凋亡率;Western blot检测凋亡相关蛋白的表达水平。结果 A549细胞在4、6、8 Gy照射时,¹²⁵I粒子组细胞克隆存活分数较⁶⁰Co组降低更明显(t=6.06、9.42、4.90,P<0.05)。A549细胞在4 Gy时,G₁期细胞比例¹²⁵I粒子组为70.67%±1.49%,⁶⁰Co组为59.59%±0.71%(t=10.77,P<0.05);细胞凋亡率¹²⁵I粒子组为18.09%±0.73%,⁶⁰Co组为9.81%±0.16%(t=19.40,P<0.05)。¹²⁵I粒子照射明显上调Bax、cleaved Caspase-3蛋白的表达,同时下调Bcl-2蛋白的表达。但不同射线同一剂量或相同射线不同剂量下,BEAS-2B细胞的凋亡率及凋亡相关蛋白的表达无明显变化。结论 ¹²⁵I粒子持续低剂量率照射较⁶⁰Co γ射线高剂量率照射抑制A549细胞增殖的效应更明显。Bcl-2/Bax蛋白比失衡,最终致Caspase-3蛋白的活化在¹²⁵I粒子持续低剂量率照射抑制肿瘤细胞增殖的效应中可能发挥重要的作用。     

miR-424*在X射线照射后的A549细胞体内、外及非小细胞肺癌组织和血清中的表达

目的 研究2、4 Gy X射线照射后人肺腺癌细胞miR-424^*体内、外表达以及非小细胞肺癌患者肺组织及血清中miR-424^*的表达变化及其意义。方法 2、4 Gy X射线分别照射体外培养的A549细胞,以实时定量PCR（RT-qPCR）法检测A549细胞中miR-424^*表达水平;用照射后的A549细胞制备裸鼠肺转移动物模型,检测裸鼠肺组织及血清中miR-424^*的表达水平;收集肺癌患者肺组织及血清样本,检测miR-424^*表达水平。结果 2、4 Gy X射线照射后1、2、12、24及48 h,miR-424^*表达均显著升高（2 Gy：t=-45.886~-6.709,P<0.05;4 Gy：t=-29.087~-7.833,P<0.05）;0、2、4 Gy照射后,miR-424^*在裸鼠肺及血清中表达水平分别为空白对照组的9.72、8.58及4.7与11.93、9.22及8.99倍（t=-13.243~-3.052,P<0.05）。6/11例（54.5%）患者肺癌组织中高表达miR-424^*,腺癌、鳞癌病理类型间检出率差异无统计学意义（P>0.05）;43/84例（51.20%）肺癌患者与健康志愿者相比,血清miR-424^*表达升高 1.97~17.71倍,其中腺癌患者血清检出率为39.1%（18/46）,鳞癌患者血清检出率为65.8%（25/38）,两种病理类型检出率差异有统计学意义（t=5.919,P<0.05）;此外,84例肺癌患者中,miR-424^*[JP3]在未接受放疗的肺癌患者血清中的阳性检出率为41.5%（22/53）,显著低于接受放疗的肺癌患者血清的阳性检出率67.7%（21/31）[JP]（t=5.387,P<0.05）。结论 2、4 Gy X射线照射可增加A549细胞miRNA-424^*的体内、外表达水平,可能与增强A549细胞体内、外侵袭转移能力有关。肺癌患者中50%以上的肺癌组织及肺癌患者血清中miR-424^*表达水平显著升高,可能与肺癌的病理类型及放疗相关。     

Decreased uptake after fractionated ablative doses of iodine-131

Purpose In an attempt to obviate the necessity for hospitalisation, the ablative dose of ¹³¹I in the treatment of thyroid cancer is divided into two or three fractions at weekly intervals in some hospitals with no special bed for ¹³¹I treatment. Thyroid stunning has been observed in patients receiving a ¹³¹I dose between 74 and 370 MBq (2–10 mCi). However, the influence of ¹³¹I uptake after administration of a higher dose, such as 1,110–1,850 MBq of ¹³¹I, has never been reported. In this study, we evaluated the degree of reduction in ¹³¹I uptake after patients received 1,480 MBq of ¹³¹I and evaluated the clinical value of fractionated ablative doses of ¹³¹I.Methods Thirty-five patients with functional thyroid cancer received a total of 4,440 MBq (120 mCi) of ¹³¹I which was divided into three fractions administered at weekly intervals. In all patients two ¹³¹I whole-body scans were performed. The first scan was performed directly prior to the second dose of ¹³¹I (7 days after the first administration of ¹³¹I), and the second scan was performed 7 days after the second administration of ¹³¹I and directly prior to the third administration. Regions of interest including the neck and lungs were drawn to calculate the uptake of ¹³¹I in the thyroid remnant and possible cervical lymph node and lung metastases.Results The mean uptake of ¹³¹I was 2.73% 7 days after the first administration, and decreased significantly to 0.26% 7 days after the second administration. The mean decrease was as high as 80.7%. The decrease in ¹³¹I uptake was significant in all patients except the two with lung metastases. In the two patients with lung metastases, no definite evidence of decreased uptake was noted; the uptake of ¹³¹I in the lung metastases even increased on the second ¹³¹I image in one of these patients. After administration of 1,480 MBq of ¹³¹I, the decreased uptake was significant in all neck lesions but not in lung metastases.Conclusion The use of fractionated ablative doses of ¹³¹I is not to be recommended in patients without lung metastases. However, the influence of fractionated ablative doses of ¹³¹I in patients with lung metastases is worthy of further study.     

Imaging,biodistribution and efficacy evaluation of 188Re-human serum albumin microspheres via intraarterial route in an orthotopic hepatoma model

Purpose: Liver cancer is the second most common cause of death worldwide. This study was to investigate the SPECT/CT, ultrasound, biodistribution and therapeutic evaluation of ¹⁸⁸Re-human serum albumin microspheres (¹⁸⁸Re-HSAM) in the GP7TB orthotopic hepatoma rat model.

Materials and methods: HSAM was labeled with ¹⁸⁸Re by using a home-made kit and microwave system. The ¹⁸⁸Re-HSAM was administered via intraarterial route. The in vivo distribution of ¹⁸⁸Re-HSAM was determined by biodistribution analysis and nanoSPECT/CT system. In efficacy, tumor volumes were tracked longitudinally by three-dimensional ultrasound.

Results: The biodistribution and nanoSPECT/CT imaging showed that ¹⁸⁸Re-HSAM could accumulate in liver and tumor. The correlation coefficient of tumor volumes done by three-dimensional ultrasound and at autopsy was 0.997. In efficacy, tumor volume in the normal saline-treated group was 1803.2?mm³ at 54 days after tumor inoculation. Tumor volumes in the 103.6 MBq and 240.5 MBq of ¹⁸⁸Re-HSAM treated groups were 381 and 267.4?mm³ (p?=?0.001 and 0.004), respectively.

Conclusions: These results show that three-dimensional ultrasound with a high spatial resolution and contrast in soft tissue can become imaging modality in assessing tumor burden and tumor progression in an orthotopic rat model. The longitudinally therapeutic evaluation of ¹⁸⁸Re-HSAM demonstrated dose-dependent tumor growth inhibition with increased dose in the GP7TB orthotopic hepatoma rat model.     

125I-脱氧尿嘧啶核苷-壳聚糖载药纳米微粒的研制和鉴定

目的 研制直径100～200 nm的¹²⁵I-脱氧尿嘧啶核苷-壳聚糖载药纳米微粒( ¹²⁵I-UdR-CS-DLN),并进一步分析其药物缓释性能和肿瘤靶向性。方法 采用离子交联法制备CS纳米微粒,以单因素分析和正交试验优化制备条件和工艺;用动态透析法分析其释放特性;激光共聚焦显微镜观察其肿瘤靶向性。结果 按照CS浓度1 g/L,搅拌速度600 r/min,TPP浓度2 g/L,相对分子质量为3×10³的条件下得到平均粒径(70.39±5.12) nm的纳米微粒(PDI为0.16±0.012)。透射电镜观察其外观为规整的球形,大小均匀,分散度较好。在投药量为2.96 MBq/ml、pH值为5的条件下, ¹²⁵I-UdR-CS-DLN的载药量1253.55 MBq/g,包封率42.35%,具有明显的缓释作用。激光共聚焦显微镜观察结果证明肿瘤细胞在2 h内摄入的纳米粒子明显多于正常细胞。结论 成功制备了直径为(127.81±15.25) nm (PDI 为0.240±0.035)的 ¹²⁵I-UdR-CS-DLN,确定了最佳工艺条件。所制备的纳米粒子具有典型的长效缓释制剂特性,并具有肿瘤细胞被动靶向性,为 ¹²⁵I-UdR应用于肿瘤内照射治疗提供了更有效的途径。     

6家医院碘治疗场所工作人员甲状腺131I活度测量

目的调查碘治疗场所工作人员甲状腺131I活度水平及其主要影响因素。方法采用配额抽样的方法, 按照碘治疗场所医院的不同类型, 在山西省和山东省共选择6家开展碘治疗的医院, 采用直接测量法, 对76名碘治疗场所工作人员的甲状腺131I活度进行了测量, 并进行内照射剂量估算。结果共有5家医院的29人甲状腺131I活度高于仪器的探测限, 占全部被检测人员的38.16%, 其中最高值为2 468.45 Bq, 是1名负责手动分装放射性碘的医师。6家医院碘治疗场所工作人员甲状腺131I活度差异无统计学意义(P>0.05), 但手动分装131I的医院测量结果高于自动分装的医院, 差异有统计学意义(Z=1.75, P<0.01), 两家手动分装131I医院的12名碘治疗场所工作人员甲状腺测量结果全部高于探测限, 中位数分别为324.59 Bq和331.98 Bq, 4家使用自动分装仪的医院测量结果的中位数均低于探测限, 甲状腺131I检出率分别为32.61%、25.00%、10.00%和0。对于同一家医院, 参与分装131I的医生和保洁人员甲状腺131I活度高于不参与分装的医生, 差异有统...     

Iodine-123 as a diagnostic imaging agent in differentiated thyroid carcinoma: a comparison with iodine-131 post-treatment scanning and serum thyroglobulin measurement

Purpose Using ¹²³I for diagnostic purposes avoids the risk of stunning for subsequent radioiodine treatment and affords an excellent image quality. In this study we assessed the role of ¹²³I in comparison with ¹³¹I post-treatment imaging in patients with thyroid cancer. Methods We compared a total of 292 ¹²³I scans with their corresponding post-treatment ¹³¹I images. Patients received a therapeutic dose of ¹³¹I following diagnostic scanning with 50–111 MBq of ¹²³I. All patients were in a hypothyroid state (>30 μIU/l) before radioiodine administration for either diagnostic or therapeutic purposes. Results In 228 out of 263 patients with a positive diagnostic scan, ¹²³I whole-body scan findings were concordant with those of corresponding post-treatment ¹³¹I images (concordance rate 87%). However, there were 44 additional foci of abnormal uptake on post-treatment ¹³¹I scans in 22 discordant cases with no impact on therapeutic management of the patients. In 13 patients, there was at least one new site on post-treatment images that had been missed on pretreatment ¹²³I images. Twenty-nine patients with a negative diagnostic scan were treated with ¹³¹I owing to a high serum thyroglobulin level (range 11.3–480 ng/ml). Radioiodine uptake sites were seen in eight post-treatment scans. In 21 pairs of whole-body scans, both the pre- and the post-treatment scan were negative (concordance rate 72.4%). Conclusion ¹²³I scanning is comparable to high-dose ¹³¹I post-treatment imaging in thyroid carcinoma patients, and ¹²³I offers excellent image quality as a diagnostic agent. It avoids disadvantages such as stunning before treatment and delivery of a high radiation dose to patients.     

Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy

We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of ¹³¹I-A7, an IgG1 anti-colorectal monoclonal antibody, or ¹³¹I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation (n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice (n=8) (P<0.05). ¹³¹I-A7 RIT displayed a marked therapeutic effect (n=8) (P<0.001); however, all animals eventually died due to metastases by 99 days. The combined regimen of ¹³¹I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy (n=10) (P<0.05); three mice survived the entire 160-day observation period. The combination of antiangiogenic therapy and ¹³¹I-HPMS-1 RIT failed to provide an appreciable benefit (n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases.     

Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with <Superscript>99m</Superscript>Tc- and <Superscript>123</Superscript>I-labelled probes

Purpose  The study serves to optimise conditions for multi-pinhole SPECT small animal imaging of ¹²³I- and ^99mTc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose range thresholds for verification of differences in tracer uptake. Methods  A Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of the dopamine D₂ receptor ligand [¹²³I]IBZM and the cerebral perfusion tracer [^99mTc]HMPAO (1.2–0.4 MBq/g body weight) in healthy mice. The fatty acid [¹²³I]IPPA (0.94 ± 0.05 MBq/g body weight) and the perfusion tracer [^99mTc]sestamibi (3.8 ± 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP₃ receptor. Results  In vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation of striatal [¹²³I]IBZM and of cardiac [^99mTc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [¹²³I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [^99mTc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [¹²³I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight. Conclusion  Multi-pinhole SPECT enables detection of alterations of the cerebral uptake of ¹²³I- and ^99mTc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Experimental radioimmunotherapy with186Re-MAG3-A7 anti-colorectal cancer monoclonal antibody: Comparison with131I-counterpart

A murine IgG1 against a Mr 45 kD tumor-associated glycoprotein in human colorectal cancer, A7, was radiolabeled with 186Re by a chelating method with a mercaptoacetyltriglycine (MAG3). Its specific activity was 119 MBq/mg, which would be high enough for a therapeutic purpose, and its immunoreactivity was preserved well as was 131I-A7 labeled by the chloramine-T method. Growth of human colon cancer xenografts, 9.14 +/- 0.44 mm in diameter, in nude mice was significantly suppressed by an intravenous dose of 4.48 MBq of 186Re-A7. The therapeutic outcome with 186Re-A7 was better than that with 4.63 MBq of 131I-A7. Toxicity of treatments assessed by body weight change was similar with both conjugates. These results are likely caused by the tumor size and more favorable physical properties of 186Re than those of 131I.