^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-FLT和18F-FDG评价食管癌细胞照射后超早期生物学反应

目的 比较18F-氟代脱氧胸腺嘧啶(18F-FLT)和18F-氟代脱氧葡萄糖(18F-FDG)在反映食管癌细胞受照后超早期生物学反应的差异.方法 将人食管癌Eca-109细胞分别接受5、10、15 Gy剂量X射线照射,照射后2、4、8h检测细胞对18F-FDG和18F-FLT摄取率的变化,以及细胞相对存活率和ATP表达情况的变化.结果 5 Gy照射后2、4h,细胞对18F-FDG摄取率与对照组相比分别减少了9.45％和16.4％,差异无统计学意义;但15 Gy照后2h,对18F-FDG摄取率却增加了26.5％(=3.04,P＜0.05),其余照射组对18F-FDG摄取率均有明显减少(F=25.75,P＜0.05).5 Gy照后2h,18F-FLT摄取率(3.65±0.41)％与对照组(4.00±0.42)％相比,差异无统计学意义,其余照射组对18F-FLT摄取率与对照组比较均有明显减少(F=33.93,P＜0.05).在5、10、15 Gy照后2、4、8h,各组细胞相对存活率差异无统计学意义.经不同剂量照射后,细胞对18F-FLT摄取率与ATP浓度之间的相关性(r=0.887,P＜0.05)优于18F-FDG与ATP浓度之间的相关性(r=0.622,P＞0.05).结论 18F-FDG和18 F-FLT两者均可反映食管癌细胞照射后超早期生物学反应,18F-FLT比18F-FDG能较好地反映食管癌细胞照射后超早期生物学反应.     

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-FLT细胞摄取率评价结直肠癌HCT116细胞早期放射反应

目的 观察不同剂量6MVX射线照射人结直肠癌细胞株HCT116后,体外细胞摄取18F-FLT的变化,分析18F-FLT用于早期预测肿瘤放射反应性的可行性.方法 测定1.0×105 ～1.5×106个细胞、培养36、60、84 h条件下,结直肠癌细胞株HCT116的18F-FLT摄取率.测定细胞经0、2、4、6、8 Gy6 MVX射线照射后,不同时间点(24、48、72 h)18F-FLT的细胞摄取率及细胞摄取抑制率;同时测定不同剂量照射后的细胞生长曲线、细胞增殖及细胞周期情况.结果 HCT116细胞对18F-FLT摄取率达(18.97 ±1.16)％.18F-FLT细胞摄取抑制率在照射2、4、6、8 Gy后24 h分别为(32.10±0.02)％、(54.46±0.04)％、(62.74±0.04)％和(65.81±4.81)％;18F-FLT细胞摄取抑制率与照射剂量呈正相关. 18F-FLT细胞摄取率与细胞周期S期比例呈正相关.结论 18F-FLT细胞摄取率可以早期反映人结直肠癌HCT116细胞株对放射的反应性.     

淋巴瘤细胞株Raji摄取~(18)F-氟脱氧葡萄糖和~(18)F-氟脱氧胸腺嘧啶核苷的体外实验研究

目的 研究测定人淋巴瘤细胞株Raji摄取~(18)F-氟脱氧葡萄糖(~(18)F-FDG)和~(18)F-氟脱氧胸腺嘧啶核苷(~(18)F-FLT)的方法并比较两者的差异.方法 在不同条件下测定淋巴瘤细胞株Raji对~(18)F-FDG和~(18)F-FLT的细胞结合率:细胞数量1×10~5～1×10~7/瓶;~(18)F-FDG和~(18)F-FLT的放射性活度1.85～29.6 kBq;反应时间20～120min;葡萄糖浓度0～11.1mmol/L.结果 每瓶1×10~7个细胞、加入3.7 kBq ~(18)F-FDG、葡萄糖浓度在0～2.78 mmol/L、作用100min,~(18)F-FDG细胞结合率达到(50.42±1.07)%;每瓶1×10~7个细胞、加入3.7 kBq ~(18)F-FLT、作用100min,~(18)F-FLT细胞结合率达到(59.48±0.77)%;~(18)F-FDG和~(18)F-FLT的细胞结合率之间具有统计学差异(F=1192.805,P<0.001).结论 Raji细胞与~(18)F-FDG的结合率与细胞数量、作用时间及葡萄糖浓度有关,与~(18)F-FDG的放射性活度无关;Raji细胞与~(18)F-FLT的结合率与细胞数量和作用时间有关,与~(18)F-FLT的放射性活度及葡萄糖浓度无关;同等条件下,Raji细胞对~(18)F-FLT的细胞结合率高于~(18)F-FDG.     

^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-FDG PET/CT评价兔VX2移植瘤对顺铂化疗的早期反应

目的 探讨18F-FDG PET/CT评价兔VX2移植瘤顺铂化疗早期反应的最佳时间,观察移植瘤摄取FDG的变化规律及其与病理变化的相关性.方法 将30只VX2荷瘤兔按随机数字表法分为5组,每组6只.化疗组在按体质量静脉注射顺铂(7 mg/kg)化疗前和化疗后6、12、24及36h分别行18F-FDG PET/CT显像;对照组用等体积的生理盐水进行干预;勾画ROI,计算SUVmax、T/NT.采用HE染色观察肿瘤细胞坏死率,TUNEL法检测细胞凋亡.统计学分析采用配对t检验、Games-Howell检验及曲线相关分析.结果 对照组干预后SUVmax为9.77±2.45,明显高于干预前(6.58±1.67;t=-5.480,P＜0.05),干预后T/NT为29.34±3.31,明显低于干预前(52.93±3.90;t=17.593,P＜0.05).化疗组化疗后6 h 18F-FDG摄取减低,SUVmax平均减低率为(11.83±8.89)％,T/NT平均减低率为(59.00±8.22)％,与对照组间的差异有统计学意义(均P＜0.05).化疗后24 h 18F-FDG摄取减低最明显,SUVmax平均减低率为(42.33±33.80)％,T/NT平均减低率为(83.50±7.69)％,与对照组和化疗后6h显像组间的差异均有统计学意义(均P＜0.05).SUVmax和T/NT变化率与凋亡指数呈正相关(r=0.750、0.794,均P＜0.05),与肿瘤细胞坏死率亦呈正相关(r=0.804、0.874,均P＜0.05).结论 18F-FDG PET/CT能够灵敏检测早期化疗反应,化疗后24 h是最佳早期化疗反应评价时间点.     

18F-FLT PET显像预测肿瘤放射敏感性的实验研究

目的 探讨18 F-FLT PET显像能否预测肿瘤放射敏感性.方法 对乳腺癌MDA-MB-231细胞和脑胶质瘤LN229细胞以6 MVX线照射0、8和16Gy后分别行克隆形成细胞存活率实验和18 F-FLT细胞摄取实验,各剂量组2种细胞的数据差异行t检验,同种细胞放疗前(0 Gy)与放疗后数据差异行单因素方差分析.将MDA-MB-237和LN229细胞分别接种至雌性BALB/c nu/nu裸鼠右后肢外侧皮下,待肿瘤直径长至10 mm时,将2种荷瘤鼠均按0、8和16 Gy分组(随机数字表法),每组20只.各组按相应剂量放疗后分别行18F-FLT PET显像和免疫组织化学检测,计算肿瘤与肌肉的SUV比值(T/M)和TK1标记指数(LITK1),并行相关性分析.结果 8Gy辐照后MDA-MB-231细胞和LN229细胞生存分数分别为(59.73±4.3)％和(93.41±3.75)％(t=-13.20,P＜0.001),16 Gy时两者生存分数分别为(43.57±4.06)％和(81.77±4.42)％(t=-14.24,P＜0.001).8Gy辐照后1 h MDA-MB-231细胞18F-FLT摄取降至(18.32±1.38) kBq/105细胞[0Gy时为(128.22±8.24) kBq/105细胞,F=266.41,P＜0.01],72h内保持在较低水平;LN229细胞辐照后1h摄取降至(9.87±1.30) kBq/105细胞[0 Gy时为(134.88±6.59) kBq/105细胞,F=346.06,P＜0.01],后逐渐增加,72 h时升至(127.17±9.08) kBq/105细胞(F =346.06,P＞0.05);16 Gy时2种细胞摄取变化基本同8Gy组.8 Gy放疗后裸鼠MDA-MB-231移植瘤18 F-FLT摄取在第1天T/M比值下降至0.78±0.39(放疗前为2.84±0.29,F=39.78,P＜0.01),后缓慢升高,在第7天时仍低于放疗前水平(F=39.78,P＜0.01);16 Gy时变化基本同8Gy组.LN229移植瘤8 Gy放疗在第1天T/M比值升高至2.41±0.47(放疗前为1.58±0.29,F=34.01,P＜0.05),后逐渐降低,到第7天降至0.66±0.32(F=34.01,P＜0.05);16 Gy放疗后18 F-FLT摄取值持续下降,至第7天降到0.44±0.22 (F=41.85,P＜0.01).2组细胞移植瘤8Gy和16 Gy放疗后18F-FLT摄取与TK1表达相关(8 Gy:r =0.67,0.73; 16 Gy:r =0.73,0.69,均P＜0.01).结论 实验结果示18F-FLT PET显像能够预测肿瘤放射敏感性,能否应用于临床需进一步研究.     

18F-FLT PET/CT与18F-FDG PET/CT在鼻咽癌诊断和分期中的应用比较

目的 通过与18F-FDG PET/CT显像对比,探讨18 F-FLT PET/CT检测鼻咽癌原发灶和颈部淋巴结转移灶的可行性.方法 12例初治且经病理确诊的鼻咽癌患者(年龄22～62岁)自愿进入该前瞻性临床研究.每位患者先行18F-FDG PET/CT检查,次日行18F-FLF PET/CT检查.至少有2位核医学科和放射科医师阅片,比较18F-FDG PET/CT和18F-FLT PET/CT图像,采用ROI技术计算鼻咽肿瘤、颈部淋巴结转移灶、正常组织对18F-FDG、18F-FLT的SUVmax、SUVmean和MTV.采用非参数Wilcoxon秩和检验比较组间摄取和MTV差异.结果 12例鼻咽癌患者病灶均明显摄取18F-FLT.18F-FLT PET/CT和18F-FDG PET/CT均可准确诊断该组病例,二者对原发灶和淋巴结转移灶的检测结果无明显差别.鼻咽癌病灶的18F-FDG和18F-FLT SUVmax分别为10.7±5.8和6.0±2.4,SUVmean分别为5.8±3.0和3.6±1.5;SUVmax和SUVmean组间差异均有统计学意义(Z=-2.589和-2.353,P均＜0.05),而 MTV在18F-FDG和8F-FLT PET/CT 2种显像方法之问的差异无统计学意义(15.9±9.2和18.1±11.1;Z=-0.786,P＞0.05).6例有颈部淋巴结转移灶患者的SUVmax、SUVmean和MTV在2种显像方法间差异均无统计学意义(8.5±6.2比6.4±2.5、5.3±4.2比3.8±1.4、6.5 ±4.8比6.0±4.4;Z=-0.734、-0.734和-0.674,P均＞0.05).18F-FLT在颞叶摄取(SUVmax 0.7±0.3)明显低于18F-FDG(SUVmax 8.3±2.7;Z=-3.062,P＜0.01),其对于原发灶颅内浸润显示较18F-FDG更清晰.结论 18F-FLT PET/CT在鼻咽癌原发灶和淋巴结转移灶的诊断效能与18F-FDG PET/CT相当,对于显示原发灶的颅底附近侵犯更有利,其临床应用值得进一步研究.     

^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.     

Early changes in [18F]FLT uptake after chemotherapy: an experimental study

This study evaluated the use of 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) for monitoring of the early effects of anticancer chemotherapy on tumour cell proliferation. Cells derived from human oesophageal squamous cell carcinoma (OSC-1) were grown for 2 days and incubated with cisplatin (CDDP), 5-fluorouracil (5-FU), methotrexate (MTX) or gemcitabine (GEM) for 4 h. Cultures were incubated with drug doses (CDDP: 0.67, 6.7, 67 micro M; 5-FU 15.4, 154, 1,540 micro M; MTX: 4.4, 44, 440 micro M; GEM: 0.0067, 0.067, 0.67 micro M) corresponding to approximately 10%-95% proliferation inhibition (MTX: 10%-75%). Treatment was stopped and cells were allowed to recover for 4, 24 or 72 h. [(18)F]FLT was added for 10-180 min. Control cultures were incubated with [(18)F]fluorodeoxyglucose (FDG). Cell counts, viability, clonogenic activity and cell cycle distribution estimated by flow cytometry were used to evaluate the cytotoxic effects of chemotherapy. Strikingly, FLT uptake per 10(5) viable cells was increased seven- to tenfold 24 h after treatment with 5-FU or MTX irrespective of dose. Thus, total FLT uptake per tissue culture exceeded that of controls despite a considerable decrease in overall cell counts due to cytostasis up to 72 h after treatment. 5-FU-treated cells showed accumulation in early S phase (overall S phase: 88% vs 42%). GEM treatment resulted in a more moderate increase in total FLT accumulation, to a maximum of fivefold at the dose close to the IC(50). In contrast, FLT accumulation was significantly reduced at cytostatic concentrations of CDDP and was still decreasing in a dose-related manner at 72 h despite considerable S phase arrest. With 5-FU or CDDP, the uptake of FDG did not differ significantly from control values 24 h after treatment. These findings demonstrate that tumour cell uptake of FLT - in contrast to that of FDG - reveals specific changes depending on the cytostatic drug used for treatment. The antimetabolites 5-FU and MTX massively increase FLT accumulation per cell independent of dose, i.e. cytotoxicity. Early after treatment, this increase is not predictive of proliferation inhibition but reflects activated salvage pathway of DNA synthesis. By contrast, CDDP results in an early decline in FLT but not in FDG uptake. This drug-specific modulation of FLT uptake has to be taken into account in positron emission tomography studies using FLT for treatment monitoring.     

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.     

3'-Deoxy-3'-18F-fluorothymidine as a proliferation imaging tracer for diagnosis of lung tumors: comparison with 2-deoxy-2-18f-fluoro-D-glucose

OBJECTIVE: The purpose of this study was to evaluate the accuracy of 3'-deoxy-3'-F-fluorothymidine (FLT) positron emission tomography (PET) for detection of lung tumor in comparison with 2-deoxy-2-F-fluoro-D-glucose (FDG) PET. METHODS: Fifty-four patients with newly diagnosed pulmonary nodules on chest computed tomographic (CT) scan suggestive of a malignant tumor were examined with both FLT and FDG PET. The intensity of uptake in lung tumors was scored. For visualized lesions, the maximum standardized uptake value (SUV) was calculated. RESULTS: Thirty-six patients were found to have lung cancer; and 18, benign lesions. Using visual analysis, the sensitivity of FLT PET for detection of lung cancer was 83%; the specificity, 83%; and the accuracy, 83%. The corresponding values for FDG PET were 97%, 50%, and 81%, respectively. The specificity of FLT PET was significantly higher than that of FDG PET. The uptake of FLT in lung cancer was significantly lower than that of FDG. Using semiquantitative analysis, the sensitivity of FLT was 86%; the specificity, 72%; and the accuracy, 81%. The corresponding values for FDG were 89%, 67%, and 81%, respectively. CONCLUSIONS: These preliminary results indicate that FLT PET may be specific for malignant tumors although uptake of FLT in lung cancer was significantly lower than that of FDG.     

Changes in 18F-fluorothymidine and 18F-fluorodeoxyglucose positron emission tomography imaging in patients with head and neck cancer treated with chemoradiotherapy

Objective

This study compared change of ¹⁸F-fluorothymidine (FLT) uptake with that of ¹⁸F-fluorodeoxyglucose (FDG) in head and neck squamous cell cancer (HNSCC) patients during and after treatment and evaluated the utility for early monitoring of response to chemoradiotherapy.

Methods

Thirty patients with newly diagnosed HNSCCs treated with concurrent chemoradiotherapy underwent FLT and FDG PET in pre-treatment (PET1), mid-treatment (PET2) and post-treatment (PET3) stages. The PET images were evaluated quantitatively using maximum standardized uptake values (SUVs). Ratios between SUVs at PET2 and PET3 were also calculated.

Results

According to the SUVs, no significant differences were found with primary site location, cellular differentiation and T category in all PET scans. About a 78 % median decrease in FLT SUV was observed at the total dose (TD) of 30 Gy and no apparent change was observed thereafter. About a 40 % decrease in FDG SUV was observed at TD 30 Gy and significant decreases were then found at the 4- and 6-week time points after the therapy. FLT PET demonstrated no recurrence regions in patients with a PET3/PET2 ratio of <1.5. In comparison, FLT SUVs in PET3 with recurrence were increased more than three times. However, no significant difference was found between the values with recurrence and those with no recurrence in FDG PET.

Conclusion

FLT PET signal change preceded FDG PET change and the increase of FLT uptake after the therapy can imply recurrence or a residual tumor. FLT PET seems promising for early evaluation of chemoradiation effects in HNSCCs.     

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.     

Use of 3′-deoxy-3′-[18F]fluorothymidine PET to monitor early responses to radiation therapy in murine SCCVII tumors

Purpose 3′-Deoxy-3′-[¹⁸F]fluorothymidine (FLT) is a promising new radiopharmaceutical for imaging cell proliferation. We evaluated whether FLT PET can be used to monitor early responses to radiation treatment. Methods C3H/HeN mice bearing murine squamous cell carcinomas were randomized to irradiation with 0, 10, or 20 Gy. Twenty-four hours later, the mice were sacrificed for histopathological and biological assessment such as cell cycle analysis, Hoechst staining, and clonogenic cell survival assay. PET scans were performed on other mice after injection of [¹⁸F]FLT or [¹⁸F]fluorodeoxyglucose (FDG) before and after radiation treatment, and tumor growth was assessed over 9 days. Results Histopathological examination detected no morphological changes 24 h after radiation treatment, but cell cycle analysis showed that irradiated tumors had a decreased fraction of cells in S phase and an increased fraction in G2–M phase, compared with nonirradiated tumors. Irradiated tumors also had a higher incidence of apoptotic features and reduced clonogenic cell survival. Tumor growth was significantly delayed in irradiated mice (p<0.001) compared with control mice. PET images showed increased tumoral uptake of both FLT and FDG before radiation treatment. Following irradiation, FLT uptake differed significantly (p=0.020) from that in control mice. In contrast, FDG uptake after irradiation did not differ significantly from that in control mice. Conclusion Our finding that tumor uptake of FLT was reduced at 24 h after radiation treatment suggests that FLT PET may be a promising imaging modality for monitoring the early effects of radiation therapy.     

Predictive value of early and late residual 18F-fluorodeoxyglucose and 18F-fluorothymidine uptake using different SUV measurements in patients with non-small-cell lung cancer treated with erlotinib

Purpose

To evaluate the predictive value of early and late residual ¹⁸F-fluorodeoxyglucose (FDG) and ¹⁸F-fluorothymidine (FLT) uptake using different SUV measurements in PET in patients with advanced non-small-cell lung cancer (NSCLC) treated with erlotinib.

Methods

We retrospectively reviewed data from 30 patients with untreated stage IV NSCLC who had undergone a combined FDG PET and FLT PET scan at 1?week (early) and 6?weeks (late) after the start of erlotinib treatment. Early and late residual FDG and FLT uptake were measured in up to five lesions per scan with different quantitative standardized uptake values (SUV_max, SUV_2Dpeak, SUV_3Dpeak, SUV₅₀, SUV_A50, SUV_A41) and compared with short-term outcome (progression vs. nonprogression after 6?weeks of erlotinib treatment). Receiver-operating characteristics (ROC) curve analysis was used to determine the optimal cut-off value for detecting nonprogression after 6?weeks. Kaplan-Meier analysis and the log-rank test were used to evaluate the association between residual uptake and progression-free survival (PFS).

Results

Nonprogression after 6?weeks was associated with a significantly lower early and late residual FDG uptake, measured with different quantitative parameters. In contrast, nonprogression after 6?weeks was not associated with early and late residual FLT uptake. Furthermore, patients with a lower early residual FDG uptake measured in terms of SUV_max and SUV_2Dpeak had a significantly prolonged PFS (282?days vs. 118?days; p?=?0.022) than patients with higher values. Similarly, lower late residual FDG uptake and early residual FLT uptake measured in terms of SUV_3Dpeak, SUV_A50 and SUV_A41, and late FLT uptake measured in terms of SUV_3Dpeak and SUV_A50 was associated with an improved PFS.

Conclusion

Early and late residual FDG uptake, measured using different quantitative SUV parameters, are predictive factors for short-term outcome in patients with advanced NSCLC treated with erlotinib. Additionally, low residual FDG and FLT uptake early and late in the course of erlotinib treatment is associated with improved PFS.     

Diagnostic performance of 18F-fluorothymidine PET/CT for primary colorectal cancer and its lymph node metastasis: comparison with 18F-fluorodeoxyglucose PET/CT

Purpose

To examine the diagnostic performance of ¹⁸F-fluorothymidine (FLT) PET/CT in primary and metastatic lymph node colorectal cancer foci in comparison with ¹⁸F-fluorodeoxyglucose (FDG) PET/CT.

Methods

The study population comprised 28 patients with 30 newly diagnosed colorectal cancers who underwent surgical resection of the primary lesion and regional lymph nodes after both FLT and FDG PET/CT. The associations between SUVmax levels and pathological factors were evaluated using the Mann-Whitney U or Kruskal-Wallis test. Differences in diagnostic indexes for detecting nodal metastasis between the two tracers were estimated using the McNemar exact or χ ² test.

Results

All 30 primary cancers (43.0?±?20.0 mm, range 14 – 85 mm) were visualized by both tracers, but none of the FLT SUVmax values exceeded the FDG SUVmax values in any of the primary cancers (6.6?±?2.4 vs. 13.6?±?5.8, p?<?0.001). The sensitivity, specificity and accuracy for detecting nodal metastasis were 41 % (15/37), 98.8 % (493/499) and 94.8 % (508/536) for FDG PET/CT, and 32 % (12/37), 98.8 % (493/499) and 94.2 % (505/536) for FLT PET/CT, respectively. The sensitivity (p?=?0.45), specificity (p?=?0.68) and accuracy (p?=?0.58) were not different between the tracers. Nodal uptake of FLT and FDG was discordant in 7 (19 %) of 37 metastatic nodes. There were ten concordant true-positive nodes of which six showed higher FDG SUVmax and four showed higher FLT SUVmax, but the difference between FDG and FLT SUVmax was not significant (5.56?±?3.55 and 3.62?±?1.45, respectively; p?=?0.22).

Conclusion

FLT has the same potential as FDG in PET/CT for the diagnosis of primary and nodal foci of colorectal cancer despite significantly lower FLT uptake in primary foci.     

Comparison of <Superscript>18</Superscript>F-FLT PET and <Superscript>18</Superscript>F-FDG PET for preoperative staging in non-small cell lung cancer

Purpose The nucleoside analog 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) has been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively compared the diagnostic efficacy of FLT PET with that of 2-deoxy-2-¹⁸F-fluoro-d-glucose (FDG) PET for the preoperative nodal and distant metastatic staging of non-small cell lung cancer (NSCLC). Methods A total of 34 patients with NSCLC underwent FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. The PET images were evaluated qualitatively for regions of focally increased metabolism. For visualized primary tumors, the maximum standardized uptake value (SUV) was calculated. Nodal stages were determined by using the American Joint Committee on Cancer staging system and surgical and histologic findings reference standards. Results For the depiction of primary tumor, sensitivity of FLT PET was 67%, compared with 94% for FDG PET (P = 0.005). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for lymph node staging on a per-patient basis were 57, 93, 67, 89, and 85%, respectively, with FLT PET and 57, 78, 36, 91, and 74%, respectively, with FDG PET (P > 0.1 for all comparisons). Two of the three distant metastases were detected with FLT and FDG PET. Conclusion In NSCLC, FLT PET showed better (although not statistically significant) specificity, positive predictive value and accuracy for N staging on a per-patient basis than FDG PET. However, FDG PET was found to have higher sensitivity for depiction of primary tumor than FLT PET.     

Compliance with PET acquisition protocols for therapeutic monitoring of erlotinib therapy in an international trial for patients with non-small cell lung cancer

Purpose

The Response Evaluation Criteria in Solid Tumors (RECIST) are widely used but have recognized limitations. Molecular imaging assessments, including changes in ¹⁸F-deoxyglucose (FDG) or ¹⁸F-deoxythymidine (FLT) uptake by positron emission tomography (PET), may provide earlier, more robust evaluation of treatment efficacy.

Methods

A prospective trial evaluated on-treatment changes in FDG and FLT PET imaging among patients with relapsed or recurrent non-small cell lung cancer treated with erlotinib to assess the relationship between PET-evaluated response and clinical outcomes. We describe an audit of compliance with the study imaging charter, to establish the feasibility of achieving methodological consistency in a multicentre setting.

Results

Patients underwent PET scans at baseline and approximately day 14 and day 56 of treatment (n?=?73, 66 and 51 studies, and n?=?73, 63 and 50 studies for FDG PET and FLT PET, respectively). Blood glucose levels were within the target range for all FDG PET scans. Charter-specified uptake times were achieved in 86% (63/73) and 89% (65/73) of baseline FDG and FLT scans, respectively. On-treatment scans were less consistent: 72% (84/117) and 68% (77/113), respectively, achieved the target of ±5?min of baseline uptake time. However, 96% (112/117) and 94% (106/113) of FDG and FLT PET studies, respectively, were within ±15?min. Bland-Altman analysis of intra-individual hepatic average standardized uptake value (SUV_ave), to assess reproducibility, showed only a small difference in physiological uptake (?0.006?±?0.224 in 118 follow-up FDG scans and 0.09?±?0.81 in 111 follow-up FLT scans).

Conclusion

It is possible to achieve high reproducibility of scan acquisition methodology, provided that strict imaging compliance guidelines are mandated in the study protocol.