NRP-1单克隆抗体对乳腺癌裸鼠移植瘤生长的影响

 目的 探讨NRP-1单克隆抗体（NRP-1 MAb）的特异性，以及不同剂量的NRP-1 MAb治疗乳腺癌裸鼠移植瘤的疗效。方法 Western blot和共聚焦免疫荧光法检测NRP-1 MAb是否识别MCF7细胞上NRP-1蛋白。将MCF7细胞接种于BALB/c裸鼠皮下建立乳腺癌细胞移植瘤模型，并进行瘤组织传代。传代的肿瘤体积生长至300~500 mm3时，随机分为对照组、NRP-1 MAb低剂量组、中剂量组和高剂量组，每组6只，给药7次。观察荷瘤裸鼠一般状况，测量瘤体大小及裸鼠体重。实验结束时剥离瘤体称重，提取组织蛋白，Western blot检测组织中VEGF蛋白和NRP-1蛋白的表达量。结果 NRP-1MAb成功识别MCF7细胞上的NRP-1蛋白；NRP-1 MAb能够有效抑制MCF7细胞裸鼠移植瘤的生长，低剂量组（1 mg/kg）抑瘤率为47.01%，中剂量组（5 mg/kg）抑瘤率为65.70%，高剂量组（10 mg/kg）抑瘤率为69.19%。。结论 NRP-1 MAb能够识别并有效结合MCF7细胞膜上的NRP-1蛋白，且可抑制MCF7细胞移植瘤的生长，NRP-1 MAb抑制移植瘤的增长可能与下调NRP-1和VEGF表达有关。     

超声应变弹性成像技术对乳腺BI-RADS4类结节级别调整的诊断价值

目的 探讨超声应变弹性成像技术中的弹性评分及应变比值(SR)对乳腺影像报告和数据系统(BI-RADS)4类结节级别调整的诊断价值.方法 收集200个常规超声BI-RADS分级诊断为BI-RADS 4类结节行应变弹性成像,获得弹性评分值和SR,并计算出两者的良恶性界值,联合这两项指标,对结节的分级重新调整.以病理结果 为...     

131I标记抗NRP-1单克隆抗体A6在荷瘤裸鼠体内分布和显像研究

目的制备131I标记的抗神经纤毛蛋白-1（NRP-1）单克隆抗体A6（131I-A6）,探讨其作为NRP-1靶向显像新型分子探针的可行性。方法（1）采用Iodogen法对A6进行131I标记,检测其标记率、放化纯和体外稳定性。（2）以人胶质瘤细胞株U87MG为实验细胞进行体外实验,测定131I—A6生物学活性、结合率及其与受体的亲和力。（3）将荷U87MG胶质瘤模型裸鼠采用随机抽样法分为5组,每组5只,分别于注射1．2MBq 131I-A6后24、48、72、96和120h处死,计算各脏器放射性摄取（％ID／g）、肿瘤／血液（T／B）和肿瘤／肌肉（T／M）比值。（4）取6只荷瘤裸鼠,以随机抽样法分为未阻断组和竞争阻断组,前组注射3．7MBq 131I-A6;后组注射3．7MBq 131I-A6和未标记的700仙gA6,均分别于注射后24、48、72、96和120h行SPECT／CT显像。采用两样本t检验对实验数据进行统计学分析。结果（1）131I—A6标记率为（95．46±3．34）％,放化纯〉95％;131I—A6在室温下PBS溶液中放置至96h,其放化纯仍〉85％。（2） 131I-A6与U87MG胶质瘤细胞特异性结合率1h达到最高值,为（15．80±1．30）％,在加入未标记的抗体A6时,U87MG细胞对131I-A6明显受抑制（t=2．862,P〈0．05）;与细胞表面抗原的亲和力（kd）为（1．67±0．14）nmol／L。（3）24h时131I—A6在荷瘤裸鼠血液放射性最高,为（8．00±1．42）％ID／g;其次是肝脏和肿瘤组织,分别为（7．68±1．56）和（6．00±1．24）％ID／g;脑、骨、肌肉组织放射性计数较低。给药后24h,T／B和T／M分别为0．78±0．10和3．20±0．30,随时间延长比值逐渐增高,在120h达到最高,分别为1．87±0．50和7．13±0．24。（4）体内显像示,注射 131I-A6后24h肿瘤略显影,随时间延长变清晰,120h显影为最清晰,阻断后未见肿瘤显影。结论 131I-A6的标记方法简单易行,标记率高,产物稳定性好,?     

99Tcm-HL91乏氧显像在恶性肿瘤治疗后随访中的应用

Objective 99Tcm-4, 9-diaza-3, 3, 10, 10-tetramethyldodecan-2, 11-dione dioxime (HL91) is a new hypoxia imaging agent that demonstrates increased uptake and retention in tumor hypoxic tissues in vivo. The objective of this study was to evaluate the clinical value of 99Tcm-HL91 hypoxia imaging in post-therapeutic patients with cancers. Methods Thirty-seven patients with primary cancers at head and neck and upper aerodigestive region who were suspected to have residual, recurrent, or metastatic disease at either clinical follow-up or by regular CT follow-up, were included. All underwent 99Tcm-HL91 imaging. The radioactivity ratios of tumor to normal tissues (T/NT) were calculated using the region of interest (ROI) technique. A t-test was used for data analysis. The " gold standard" of diagnostic accuracy was based on histopathology or clinical follow-up. Results were compared between 99Tcm-HL91 and CT. Results Of the 37 patients, 11 had either residual or recurrent lesions and 7 had distant disease. (1) A significantly higher 99Tcm-HL91 uptake were noted in residual or recurrent lesions than benign lesions (1.58 ± 0. 16 vs 1.18 ±0.14, t =4. 87, P <0.001). (2) The sensitivity, specificity, and accuracy for residual or recur-rent lesions were 72. 73% (8/11), 63.64% (7/11), 4/4; 89.47% (17/19), 84. 21% (16/19), 94. 12% (16/17), and 83.33% (25/30), 76.67% (23/30), 95.24% (20/21) in 99Tcm-HL91, CT, and combined 99Tcm-HL91 and CT, respectively. (3) For distant sites detection (n = 7), CT detected all but 99Tcm-HL91 missed three. Conclusions A combination of 99Tcm-HL91 and CT in detection either residu-al, recurrent, or metastatic disease would have the highest benefit in patients with cancers at head and neck and upper aerodigestive region.     

99mTC-MIBI显像在肿瘤临床中的应用

恶性肿瘤是目前引起人类死亡的主要疾病之一。由于其病因复杂、尚未清楚，无法预防，故肿瘤的早期诊断、早期治疗至关重要。X线检查、B超、XCT、MRI等虽已成为诊断肿瘤的重要手段，但它们成像是由组织密度不同所决定，属于形态学(解剖学)的诊断。放射性核素肿瘤显像基于组织血流、细胞代谢及活力等功能状态，属于功能性诊断，因而更适合于肿瘤早期诊断。 既往的研究表明，201Tl因在探测肿瘤代谢活力方面具有高度的特异性而广泛应用于肿瘤的早期诊断。99mTCMIBI(99m锝甲氧基异丁基异晴)与201Tl有许多极其相似之处，两者都是非常好的心肌灌注显像剂，并且99mTCMIBI物理性能优于201Tl，更适合于SPECT(单光子发射型计算机断层)显像，图像也比201Tl清晰。因此,使用99mTCMIBI进行肿瘤显像具有临床实用价值。1987年，Muller等[1]报道了在对1例甲状腺癌患者行心肌灌注显像时,发现其肺部转移灶有99mTCMIBI浓聚，这引起国内外核医学界的极大关注。此后，99mTCMIBI作为肿瘤阳性显像剂，广泛用于肿瘤定位、定性诊断、肿瘤临床分期判断、预测化疗反应及评估疗效。现就99mTCMIBI显像在肿瘤临床中的应用综述如下。     

核素内照射治疗在血管成型术后预防再狭窄的？…

血管成型术后发生再狭窄严重影响术后的近期疗效，是目前临床上急需探讨和解决的一大难题。放射性核素内照射治疗预防血管盛开 后再狭窄经动物作初步临床应用已取得了一定效果，有望成为一种在临床上防治血管成型术后再狭窄的可行有效新方法。     

TSPO靶向分子探针CB86-DTPA-Gd的制备及类风湿关节炎模型MRI研究

目的制备相对分子质量1.8×104转位蛋白(TSPO)靶向分子探针2-(8-氨基-2-(4-氯苯基)咪唑[1,2-a]吡啶-3-基)-N,N-二丙基乙酰胺(CB86)-二乙撑三胺五乙酸(DTPA)-Gd,探究其在类风湿关节炎(RA)模型的MRI效果。方法通过偶联双功能螯合剂制备CB86-DTPA,再与Gd螯合获得MRI靶向造影剂CB86-DTPA-Gd,测定其细胞毒性、MR弛豫率和体外稳定性。采用弗氏佐剂建立小鼠右踝RA模型,进行生物分布研究及MRI,以右踝关节炎性反应部位及其周围正常组织作为感兴趣区(ROI)计算信噪比(SNR)。采用两独立样本t检验分析数据。结果CB86-DTPA-Gd的MR纵向弛豫率r1为11.05 mmol·L-1·s-1。在Gd3+最大浓度(20μmol/L)时,小鼠巨噬细胞RAW264.7和小鼠乳腺癌4T1细胞的存活率均大于90%。室温下,CB86-DTPA-Gd在人血清和磷酸盐缓冲溶液(PBS;pH=7.4)中的稳定性良好。体内生物分布研究表明,CB86-DTPA-Gd具有较好的炎性反应靶向性,注射后120 min踝关节炎性反应部位摄取仍达(2.33±0.29)每克组织百分注射剂量率(%ID/g)。MicroMRI结果显示,右踝关节炎性反应部位在注射CB86-DTPA-Gd和Gd-DTPA后均表现为明显强化,CB86-DTPA-Gd组SNR最高可达23.21±1.44,最大强化时间为注射后90 min,且各时间点均能被CB86-DTPA所抑制(t值:6.083~12.451,均P<0.05),而Gd-DTPA组强化时间为注射后30 min,SNR为16.12±1.24。结论CB86-DTPA-Gd显示了良好的巨噬细胞靶向性,在关节炎性反应部位有良好的摄取,有望成为一种用于外周炎性反应显像的新型MRI分子探针。     

小胶质细胞在神经退行性疾病发生发展中的双重作用

小胶细胞是中枢神经系统的主要免疫细胞,当中枢神经系统受到损伤时,就被激活,一方面产生大量致炎性细胞因子和神经元毒性介质,介导脑内慢性炎症反应、细胞凋亡,导致神经元损伤、死亡;另一方面激活的小胶质细胞也发挥吞噬作用和分泌神经生长因子,具有保护中枢神经系统的功能。本文着重阐述小胶质细胞的双重作用,并对目前一些针对小胶细胞治疗作个介绍。     

99Tcm-HL91乏氧显像在恶性肿瘤治疗后随访中的应用

Objective 99Tcm-4, 9-diaza-3, 3, 10, 10-tetramethyldodecan-2, 11-dione dioxime (HL91) is a new hypoxia imaging agent that demonstrates increased uptake and retention in tumor hypoxic tissues in vivo. The objective of this study was to evaluate the clinical value of 99Tcm-HL91 hypoxia imaging in post-therapeutic patients with cancers. Methods Thirty-seven patients with primary cancers at head and neck and upper aerodigestive region who were suspected to have residual, recurrent, or metastatic disease at either clinical follow-up or by regular CT follow-up, were included. All underwent 99Tcm-HL91 imaging. The radioactivity ratios of tumor to normal tissues (T/NT) were calculated using the region of interest (ROI) technique. A t-test was used for data analysis. The " gold standard" of diagnostic accuracy was based on histopathology or clinical follow-up. Results were compared between 99Tcm-HL91 and CT. Results Of the 37 patients, 11 had either residual or recurrent lesions and 7 had distant disease. (1) A significantly higher 99Tcm-HL91 uptake were noted in residual or recurrent lesions than benign lesions (1.58 ± 0. 16 vs 1.18 ±0.14, t =4. 87, P <0.001). (2) The sensitivity, specificity, and accuracy for residual or recur-rent lesions were 72. 73% (8/11), 63.64% (7/11), 4/4; 89.47% (17/19), 84. 21% (16/19), 94. 12% (16/17), and 83.33% (25/30), 76.67% (23/30), 95.24% (20/21) in 99Tcm-HL91, CT, and combined 99Tcm-HL91 and CT, respectively. (3) For distant sites detection (n = 7), CT detected all but 99Tcm-HL91 missed three. Conclusions A combination of 99Tcm-HL91 and CT in detection either residu-al, recurrent, or metastatic disease would have the highest benefit in patients with cancers at head and neck and upper aerodigestive region.