18F-FLT及18F-FDG监测肺癌化疗后早期反应的动物实验

18F-脱氧葡萄糖(fluorodeoxyglucose,FDG)在肺癌的诊断及疗效监测中有重要的作用,但特异性较差,存在一定的假阳性.18F-脱氧胸腺嘧啶核苷(fluorothymidine,FLT)是核酸代谢显像剂.笔者观察了经紫杉醇+顺铂治疗后1d的荷肺癌裸小鼠的18F-FLT和18F-FDG生物分布,及肿瘤增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达,并进行比较.     

18F-FLT及18F-FDG监测肺癌化疗后早期反应的动物实验

18F-脱氧葡萄糖(fluorodeoxyglucose,FDG)在肺癌的诊断及疗效监测中有重要的作用,但特异性较差,存在一定的假阳性.18F-脱氧胸腺嘧啶核苷(fluorothymidine,FLT)是核酸代谢显像剂.笔者观察了经紫杉醇+顺铂治疗后1d的荷肺癌裸小鼠的18F-FLT和18F-FDG生物分布,及肿瘤增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达,并进行比较.     

^18F-FLT和^18F-FDG PET显像早期评估荷肺腺癌小鼠放疗疗效

目的:比较18F-FLT和18F-FDG早期评估荷肺腺癌小鼠放疗疗效.材料和方法:24只T739荷肺腺癌小鼠随机分为18F-FLT和18F-FDG两组,各组再分为对照组和放疗组.放疗组接受20Gy的X线放射治疗后2天,各组小鼠经尾静脉注入18F-FLT和18F-FDG60min后行PET显像并井形探测仪测量活性分布.肿瘤增殖判定采用免疫组织化学方法测定PCNA.结果:放疗后肿瘤18F-FLT摄取较对照组明显降低(0.37±0.12%和1.25±0.19%,P<0.01),而18F-FDG摄取变化不明显.PET显像18F-FLTSUVmax值低于对照组,18F-FDG摄取变化不明显.肿瘤18F-FLT摄取与PCNA指数显著相关(r=0.8805),18F-FDG摄取与PCNA无相关性.结论:放疗后18F-FLT摄取降低较18F-FDG明显,与PCNA指数显著相关,因而18F-FLT是一种监测肿瘤治疗疗效的有前途的示踪剂.     

^18F-FDG PET/CT代谢参数评估食管癌新辅助放化疗效果

食管癌新辅助放化疗后组织病理反应程度能预测患者远期生存,指导调整后续治疗方案.^18F-FDG PET/CT能够通过代谢变化评估肿瘤组织病理反应,具体参数包括治疗后SUV、治疗前后SUV降低百分比（△SUV％）,以及治疗前后肿瘤长度变化百分比（△L％）等.目前哪项参数在预测食管癌放化疗后组织病理反应中最有效尚无定论.本研究通过观察各参数预测食管癌组织病理反应的精确性,以及代谢反应和组织病理学反应分层的生存率曲线差异情况,寻求最佳预测参数.     

^18F-FLT实验研究与临床应用进展

放射性核素标记的胸腺嘧啶类似物能够在一定程度上反映细胞增殖的状况，3’-脱氧-3’-^18F-氟代胸苷(3’-deoxy-3’-’^18F-fluorothymidine，^18F-FLT)是此类药物中发展较为完善的一种示踪剂。^18F-FLT PET通过反映胸苷激酶-l的活性而间接反映肿瘤细胞的增殖状况，有助于对肿瘤进行良恶性鉴别、疗效评估和预后判断，是一种具有良好应用前景的PET显像剂。     

18F-FLT体外监测结肠癌细胞早期放射反应

Objective To evaluate whether 18F-fluorothymidine(FLT) can be used to monitor early response to irradiation in colorectal cancer (CRC).Methods SW480 cells were cultured and irradiated with 0, 10, and 20 Gy.Twenty-four hours later, morphological changes, apoptosis, necrosis, proliferation,and cell cycle phases were observed.Uptake of 18F-FLT was measured in these tumors in vitro from 24 h to 72 h after irradiation.The one-way analysis of variance was used to analyze the data.Results Apoptotic and necrotic cells were detected 24 h after radiotherapy.SW480 cells proliferation was significantly delayed after irradiation in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide (MTI) assay.Cell cycle analysis showed that SW480 cells had a decreased fraction of cells in S phase( from 33.23% to 9.24%,then to 5.43% ) and an arrested fraction in G0-G1.After SW480 cells were cultured for60 min, the uptake of 18F-FLT was (5.21 ± 1.60) %; and 24 h after irradiation of 10 Gy, the uptake decreased significantly to (4.27±0.48)% (F=8.253, P=0.009).And 72 h after irradiation, the uptake further decreased significantly to (3.39 ± 0.59) % ( F = 36.715, P＜0.001 ).In tumor tissue, the uptake of 18F-FLT reduced significantly 72 h after radiotherapy (10 Gy:F = 12.388, P = 0.007; 20 Gy:F = 16.744, P = 0.004) and the attenuation degree increased with the radiation dose.Conclusion The uptake of 18F-FLT in SW480 cells or in CRC could reflect the changes of SW480 cells in proliferation, cell cycle re-distribution, cell apoptosis and necrosis.The results suggest that 18F-FLT may be used for monitoring early response to irradiation of CRC.     

18F-FLT体外监测结肠癌细胞早期放射反应

Objective To evaluate whether 18F-fluorothymidine(FLT) can be used to monitor early response to irradiation in colorectal cancer (CRC).Methods SW480 cells were cultured and irradiated with 0, 10, and 20 Gy.Twenty-four hours later, morphological changes, apoptosis, necrosis, proliferation,and cell cycle phases were observed.Uptake of 18F-FLT was measured in these tumors in vitro from 24 h to 72 h after irradiation.The one-way analysis of variance was used to analyze the data.Results Apoptotic and necrotic cells were detected 24 h after radiotherapy.SW480 cells proliferation was significantly delayed after irradiation in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide (MTI) assay.Cell cycle analysis showed that SW480 cells had a decreased fraction of cells in S phase( from 33.23% to 9.24%,then to 5.43% ) and an arrested fraction in G0-G1.After SW480 cells were cultured for60 min, the uptake of 18F-FLT was (5.21 ± 1.60) %; and 24 h after irradiation of 10 Gy, the uptake decreased significantly to (4.27±0.48)% (F=8.253, P=0.009).And 72 h after irradiation, the uptake further decreased significantly to (3.39 ± 0.59) % ( F = 36.715, P＜0.001 ).In tumor tissue, the uptake of 18F-FLT reduced significantly 72 h after radiotherapy (10 Gy:F = 12.388, P = 0.007; 20 Gy:F = 16.744, P = 0.004) and the attenuation degree increased with the radiation dose.Conclusion The uptake of 18F-FLT in SW480 cells or in CRC could reflect the changes of SW480 cells in proliferation, cell cycle re-distribution, cell apoptosis and necrosis.The results suggest that 18F-FLT may be used for monitoring early response to irradiation of CRC.     

18F-FLT体外监测结肠癌细胞早期放射反应

目的 评价18F-脱氧胸腺嘧啶核苷（FLT）监测结肠癌细胞早期放射反应的作用.方法 应用四甲基偶氮唑蓝（MTT）检测并绘制SW480细胞受X线照射后生长曲线,光学显微镜下观察细胞形态变化.流式细胞仪检测照射后肿瘤细胞增殖周期的重新分布.分别于体外细胞以及肿瘤内检测照射前、后细胞摄取18F-FLT的变化.将18F-FLT（0.05±0.01）MBq加入培养液孵育细胞,分别于30,60,90,120 min测定细胞摄取18F-FLT的放射性.经荷瘤裸鼠尾静脉注射18F-FLT（1.90±0.85）MBq（0.25 ml）,60 min后处死动物,切除肿瘤与肌肉、肺、肝等,测定肿瘤与其他脏器摄取放射性比值变化.应用单因素方差分析进行统计学处理.结果 X线照射后,SW480细胞增殖受到明显的抑制,呈剂量依赖性.细胞形态随照射剂量的不同发生不同的变化.照射后细胞周期发生重新分布.10 Gy组,S期细胞百分比24 h从33.23%降至15.19%,72 h后降至12.44%.20 Gy组,S期细胞百分比24 h后从33.23%降至9.24%,72 h后降至5.43%.体外摄取实验发现,注射后60 min,SW480细胞摄取18F-FLT百分比为（5.21±1.60）%,10 Gy照射24 h后下降至（4.27±0.48）%,72 h降至（3.39±0.59）%.20 Gy组：照射后24 h,SW480摄取的放射性百分比下降至（3.41±0.58）%,72 h后降至（1.63±0.49）%.两照射组在72 h内分别下降了34.94%,69.72%（24 h∶F=8.253,P=0.009;72 h∶F=36.715,P＜0.001）.单位质量肿瘤组织摄取的18F-FLT随照射剂量的增加而逐渐降低（10Gy组：F=12.388,P=0.007;20 Gy组：F=16.744,P=0.004）.结论 18F-FLT在结肠癌细胞内的摄取可以快速反映照射治疗后的细胞变化,18F-FLT可能用于检测结肠癌放射治疗早期反应.     

18F-FDG和18F-FLT PET-CT在肿瘤非手术治疗早期疗效评价中的应用

早期监测肿瘤在不同治疗方法中的疗效已成为临床上亟待解决的问题.PET可从分子水平上观察细胞生物学行为,尤其是对肿瘤的早期诊断、分期及疗效评价具有较高的特异度.18F-FDG为葡萄糖类代谢显像剂,作为目前应用最为广泛的显像剂,因其本身固有的一些特点表现为对肿瘤的非特异性显像.3'-脱氧-3'-18F-氟胸腺嘧啶(18F-FLT)为核苷酸类代谢显像剂,在细胞增殖显像方面的应用较为广泛.两者在肿瘤监测、分期及疗效评价方面各具特点.该文就PET-CT在肿瘤疗效评价中的应用进行综述,同时探讨两者在监测非手术治疗疗效时何者更具有优势.     

肺癌18F-FLT PET和18F-FDG PET的临床对比研究

目的 探讨18F-FLT PET在肺癌诊断和肿瘤增殖检测方面的应用价值.方法 对2005年9月-2008年10月解放军总医院收治的36例(男27例,女9例,年龄38～74岁)胸部CT疑似肺癌患者进行18F-FLT PET扫描,对同期收治的42例(男29例,女13例,年龄37～75岁)胸部CT疑似肺癌患者进行18F-FD...     

^18F-FDG和^18F—FLTPET／CT诊断肺结节影响因素的多中心临床研究

目的:探讨18F-FDG和18F-FLT PET/CT诊断肺结节的影响因素,以提高PET/CT对肺结节的诊断价值.材料和方法:选择肺结节患者55例为研究对象,其中男性33例,女性22例,年龄17～82岁,28例为肺内孤立结节,其余为2～3个结节,结节大小0.6～11.0cm,所有患者均行肺部18F-FDG和18F-FLT PET/CT检查,分析18F-FDG和18F-FLT标准摄取值(SUV)与肺结节患者的性别、年龄、结节大小及病理类型等相互关系和意义.结果:55例肺结节患者,18F-FDG和18F-FLT标准摄取值与患者的性别、年龄、结节大小等均无统计学差异(P>0.05),18F-FDG标准摄取值与患者的病理类型亦无统计学差异(P>0.05),而18F-FLT标准摄取值与患者的病理类型有统计学差异(P<0.05).结论:肺结节患者结节的病理类型是影响18F-FLT标准摄取值的重要因素.18F-FLT PET/CT鉴别诊断肺结节良恶性具有重要的价值和意义.     

^18F-FLT和^18F-FDG诊断孤立性肺结节误诊原因分析

目的:比较18F-FLT、18F-FDG PET显像诊断SPNs的敏感性和特异性,分析误诊原因.材料和方法:55例胸部SPNs患者行18F-FLT、18F-FDG PET显像,以术后病理或随访一年为最后诊断标准,证实肺癌16例、肺结核16例、肺炎13例、良性增生10例.根据对照最后诊断,选择假阳性和假阴性的病例进行分析.结果18F-FDG显像:16例肿瘤患者中假阴性2例.16例结核患者中,9例假阳性(SUVmax>2.56).13例炎性患者中,大部分轻度摄取18F-FDG,2例假阳性SUVmax>10.10例良性结节不同程度摄取18F-FDG.18F-FLT显像:16例肿瘤患者中,5例假阴性.16例结核患者中,3例假阳性(SUVmax>2.0).13例炎症,2例假阳性.10例良性结节3例假阳性.结论:18F-FDG和18F-FLT均非肿瘤特异性示踪剂,假阴性见于低活动度或小病灶;而假阳性原因为炎症活动期和肉芽肿形成期.18F-FLT的特异度高于18F-FDG.     

PET/CT显像淋巴瘤病灶18F-FDG摄取程度与肿瘤增殖性抗原Ki-67相关性研究

目的:通过对比50例不同病理亚型的淋巴瘤肿瘤增殖性抗原Ki-67表达水平与"F-FDG PET显像病灶"F-FDG浓聚程度来探讨两者之间相关性.方法:收集50例经病理及免疫组化证实的淋巴瘤病例,每个病例均有酶标肿瘤增殖性抗原Ki-67染色免疫组化报告,病理检查前或后常规行PET/CT检查.病理分型均采用WHO分类标准,并对非霍奇金淋巴瘤例按WF分类标准对其进行大小细胞类型归类.Ki-67酶标染色结果统一采用分级方法:核抗原染色阳性细胞百分数为0～5%,表示为微弱阳性(+/-);百分数为5%～20%,表示为弱阳性(+);百分数为20%～50%,表示为中阳性(++);百分数大于50%,表示为强阳性(+++).PET/CT影像上,病灶18F-FDG摄取程度采用半定量分析方法,计算出病灶平均标准化摄取值SUV(SUVave).利用统计软件(SPSS13.0)计算不同病理亚型的病灶18F-FDG摄取值(以x±s表示),并对大、小细胞类型淋巴瘤的FDG摄取值差异显著性行t检验;对所有病灶Ki-67表达水平与18F-FDG摄取程度两者之间采用Spearman方法进行相关性分析.结果:大细胞来源的淋巴瘤18F-FDG摄取值远高于小细胞来源的淋巴瘤18F-FDG摄取值,特别是B系大小细胞不同类型淋巴瘤.其18F-FDG摄取值差异性更显著;Ki-67表达水平同结性与结外病灶18F-FDG摄取值两者存在显著相关性,r值分别为0.750和0.843.结论:反映肿瘤增殖活性的Ki-67与淋巴瘤病灶18F-FDG摄取程度有明显关系,Ki-67表达程度较高的大细胞性进展性淋巴瘤,其病灶18F-FDG摄取值很高,而Ki-67表达程度较低的小细胞性低度恶性淋巴瘤,其18F-FDG摄取值较低.     

Detection of gastric cancer using <Superscript>18</Superscript>F-FLT PET: comparison with <Superscript>18</Superscript>F-FDG PET

Purpose  We prospectively investigated the feasibility of 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) positron emission tomography (PET) for the detection of gastric cancer, in comparison with 2-deoxy-2-¹⁸F-fluoro-d-glucose (FDG) PET, and determined the degree of correlation between the two radiotracers and proliferative activity as indicated by Ki-67 index. Methods  A total of 21 patients with newly diagnosed advanced gastric cancer were examined with FLT PET and FDG PET. Tumour lesions were identified as areas of focally increased uptake, exceeding that of surrounding normal tissue. For semiquantitative analysis, the maximal standardized uptake value (SUV) was calculated. Results  For detection of advanced gastric cancer, the sensitivities of FLT PET and FDG PET were 95.2% and 95.0%, respectively. The mean (±SD) SUV for FLT (7.0 ± 3.3) was significantly lower than that for FDG (9.4 ± 6.3 p < 0.05). The mean FLT SUV and FDG SUV in nonintestinal tumours were higher than in intestinal tumours, although the difference was not statistically significant. The mean (±SD) FLT SUV in poorly differentiated tumours (8.5 ± 3.5) was significantly higher than that in well and moderately differentiated tumours (5.3 ± 2.1; p < 0.04). The mean FDG SUV in poorly differentiated tumours was higher than in well and moderately differentiated tumours, although the difference was not statistically significant. There was no significant correlation between Ki-67 index and either FLT SUV or FDG SUV. Conclusion  FLT PET showed as high a sensitivity as FDG PET for the detection of gastric cancer, although uptake of FLT in gastric cancer was significantly lower than that of FDG.     

Correlation of <Superscript>18</Superscript>F-FLT and <Superscript>18</Superscript>F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer

Purpose The nucleoside analogue 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) has recently been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively evaluated whether FLT uptake reflects proliferative activity as indicated by the Ki-67 index in non-small cell lung cancer (NSCLC), in comparison with 2-deoxy-2-¹⁸F-fluoro-D-glucose (FDG). Methods A total of 18 patients with newly diagnosed NSCLC were examined with both FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. Tumour lesions were identified as areas of focally increased uptake, exceeding background uptake in the lungs. For semi-quantitative analysis, the maximum standardised uptake value (SUV) was calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with SUVs. Results The sensitivity of FLT and FDG PET for the detection of lung cancer was 72% and 89%, respectively. Four of the five false-negative FLT PET findings occurred in bronchiolo-alveolar carcinoma. The mean FLT SUV was significantly lower than the mean FDG SUV. A significant correlation was observed between FLT SUV and Ki-67 index (r = 0.77; p < 0.0002) and for FDG SUV (r = 0.81; p < 0.0001). Conclusion The results of this preliminary study suggest that, compared with FDG, FLT may be less sensitive for primary staging in patients with NSCLC. Although FLT uptake correlated significantly with proliferative activity in NSCLC, the correlation was not better than that for FDG uptake.     

18F-FDG代谢显像对原发性乳腺癌的诊断价值

目的探讨利用符合线路(DHC)18F-FDG代谢显像对原发性乳腺癌鉴别诊断的临床价值.方法51例乳腺包块患者行DHC18F-FDG代谢显像,利用计算机感兴趣区(ROI)技术,计算靶/非靶比值(T/NT),全部患者均显像后经细针穿刺组织学活检确诊分为良性组和恶性组.结果活检病理组织学确诊乳腺癌33例(65%),良性乳腺包块18例(35%);定性诊断18F-FDG代谢显像33例,恶性患者中29例显像阳性,4例阴性;良性组3例为阳性,其余为阴性;DHC18F-FDG显像定性诊断的灵敏度、特异性和准确度分别为88%、83%和86%.恶性组和良性组摄取18F-FDG的T/NT比值分别为2.25±0.18和1.35±0.37(P＜0.01);以T/NT比值1.5为诊断阈值,DHC18F-FDG显像诊断的灵敏度、特异性和准确度分别为94%、89%和92%.结论 DHC18F-FDG显像诊断乳腺癌具有一定的临床价值,定性与定量结合有利于提高诊断效能.     

肿瘤患者心肌摄取18F-FDG程度与血糖水平的关系

目的研究血糖水平对心肌摄取18F-氟脱氧葡萄糖的影响.方法在406例符合探测检查的肿瘤患者中,选取心脏在显像范围内,且临床资料完整的141名患者.进行18F-氟脱氧葡萄糖肿瘤检测,分析心肌影像质量的分析,对比研究心肌摄取18F-氟脱氧葡萄糖的程度和血糖水平的关系.结果141例肿瘤检测患者心肌摄取18F-氟脱氧葡萄糖的程度与血糖水平无相关性(P＞0.05).结论肿瘤患者的心肌对18F-氟脱氧葡萄糖的摄取程度可能受血糖水平以外的其他因素影响,因此检查前血糖水平不能预测心肌显影的质量.     

~(18)F-FDG PET-CT扫描在消化道肿瘤中的临床应用价值

目的探讨18F-双脱氧葡萄糖(18F-FDG)正电子发射计算机断层扫描显像(PET-CT)在消化道肿瘤诊断、分期及手术后复发监测的临床应用价值。方法对50例消化道肿瘤患者进行PET-CT全身扫描,结合手术后病理、内镜、多种影像学检查及临床随访等资料,对PET-CT的临床应用价值进行评估。结果50例患者中,PET-CT显像假阳性1例,假阴性5例,与临床符合44例,符合率88%。结论18F-FDG PET-CT在消化道肿瘤诊断、分期及手术后复发监测方面有较高的临床价值,对临床治疗有重大指导作用。