Usefulness of 11C-methionine for differentiating tumors from granulomas in experimental rat models: a comparison with 18F-FDG and 18F-FLT.

Many clinical PET studies have shown that increased (18)F-FDG uptake is not specific to malignant tumors. (18)F-FDG is also taken up in inflammatory lesions, particularly in granulomatous lesions such as sarcoidosis or active inflammatory processes after chemoradiotherapy, making it difficult to differentiate malignant tumors from benign lesions, and is the main source of false-positive (18)F-FDG PET findings in oncology. These problems may be overcome by multitracer studies using 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) or l-(11)C-methionine. However, (18)F-FLT or (11)C-methionine uptake in granulomatous lesions remains unclarified. In this study, the potentials of (18)F-FLT and (11)C-methionine in differentiating malignant tumors from granulomas were compared with (18)F-FDG using experimental rat models. METHODS: Dual-tracer tissue distribution studies using (18)F-FDG and (3)H-FLT (groups I and III) or (18)F-FDG and (14)C-methionine (groups II and IV) were performed on rats bearing both granulomas (Mycobacterium bovis bacillus Calmette-Guérin [BCG]-induced) and hepatomas (KDH-8-induced) (groups I and II) or on rats bearing both turpentine oil-induced inflammation and hepatomas (groups III and IV). One hour after the injection of a mixture of (18)F-FDG and (3)H-FLT or of (18)F-FDG and (14)C-methionine, tissues were excised to determine the radioactivities of (18)F-FDG, (3)H-FLT, and (14)C-methionine (differential uptake ratio). RESULTS: Mature epithelioid cell granuloma formation and massive lymphocyte infiltration were observed in the granuloma tissue induced by BCG, histologically similar to sarcoidosis. The granulomas showed high (18)F-FDG uptake comparable to that in the hepatomas (group I, 8.18 +/- 2.40 vs. 9.13 +/- 1.52, P = NS; group II, 8.43 +/- 1.45 vs. 8.91 +/- 2.32, P = NS). (14)C-Methionine uptake in the granuloma was significantly lower than that in the hepatoma (1.31 +/- 0.22 vs. 2.47 +/- 0.60, P < 0.01), whereas (3)H-FLT uptake in the granuloma was comparable to that in the hepatoma (1.98 +/- 0.70 vs. 2.30 +/- 0.67, P = NS). Mean uptake of (18)F-FDG, (3)H-FLT, and (14)C-methionine was markedly lower in the turpentine oil-induced inflammation than in the tumor. CONCLUSION: (14)C-Methionine uptake was significantly lower in the granuloma than in the tumor, whereas (18)F-FDG and (3)H-FLT were not able to differentiate granulomas from tumors. These results suggest that (14)C-methionine has the potential to accurately differentiate malignant tumors from benign lesions, particularly granulomatous lesions, providing a biologic basis for clinical PET studies.     

Comparison of F-FDG, F-FET and F-FLT for differentiation between tumor and inflammation in rats

IntroductionThe goal of this study was to compare the glucose analog, 2-[¹⁸F]fluoro-2-deoxy-d-glucose ([¹⁸F]-FDG), the amino acid analog, o-(2-[¹⁸F]fluoroethyl)-l-tyrosine ([¹⁸F]-FET) and nucleoside analog, 3′-[¹⁸F]fluoro-3′-deoxythymidine ([¹⁸F]-FLT) with regard to their feasibility for differentiating tumors from inflammation.MethodsIn Fisher rat models bearing both 9L tumor and inflammation, the biodistributions and positron emission tomography (PET) images of [¹⁸F]-FDG, [¹⁸F]-FET and [¹⁸F]-FLT at 60 min post injection were compared. Pretreatment with thymidine phosphorylase before injection of [¹⁸F]-FLT was performed.ResultsThe tumor-to-blood (T/B) and tumor-to-muscle (T/M) ratios of [¹⁸F]-FDG were significantly higher than those of [¹⁸F]-FET and [¹⁸F]-FLT (P<.01); however, the accumulation of [¹⁸F]-FDG [1.23±0.52 percent injected dose per gram of tissue (%ID/g)] in inflammation was also elevated. T/B and T/M ratios of [¹⁸F]-FET (2.3±0.5 and 2.2±0.5) were higher than those of [¹⁸F]-FLT (1.6±0.6 and 1.6±0.5), and inflammation uptake of those tracers was very low (0.63±0.19 and 0.27±0.16 %ID/g, respectively). [¹⁸F]-FET and [¹⁸F]-FLT showed higher selectivity indices (tumor-to-inflammation ratio corrected background) than [¹⁸F]-FDG. In PET images, [¹⁸F]-FDG was found to be accumulated in both tumor and inflammation, but [¹⁸F]-FET and [¹⁸F]-FLT selectively localized in tumor.ConclusionOur data confirm the result of previous studies that [¹⁸F]-FET and [¹⁸F]-FLT are superior to [¹⁸F]-FDG in differentiating tumor from inflammation.     

Comparison of 18F-FLT PET and 18F-FDG PET in esophageal cancer.

18F-FDG PET has gained acceptance for staging of esophageal cancer. However, FDG is not tumor specific and false-positive results may occur by accumulation of FDG in benign tissue. The tracer 18F-fluoro-3'-deoxy-3'-L-fluorothymidine (18F-FLT) might not have these drawbacks. The aim of this study was to investigate the feasibility of 18F-FLT PET for the detection and staging of esophageal cancer and to compare 18F-FLT PET with 18F-FDG PET. Furthermore, the correlation between 18F-FLT and 18F-FDG uptake and proliferation of the tumor was investigated. METHODS: Ten patients with biopsy-proven cancer of the esophagus or gastroesophageal junction were staged with CT, endoscopic ultrasonography, and ultrasound of the neck. In addition, all patients underwent a whole-body 18F-FLT PET and 18F-FDG PET. Standardized uptake values were compared with proliferation expressed by Ki-67 positivity. RESULTS: 18F-FDG PET was able to detect all esophageal cancers, whereas 18F-FLT PET visualized the tumor in 8 of 10 patients. Both 18F-FDG PET and 18F-FLT PET detected lymph node metastases in 2 of 8 patients. 18F-FDG PET detected 1 cervical lymph node that was missed on 18F-FLT PET, whereas 18F-FDG PET showed uptake in benign lesions in 2 patients. The uptake of 18F-FDG (median standardized uptake value [SUV(mean)], 6.0) was significantly higher than 18F-FLT (median SUV(mean), 3.4). Neither 18F-FDG maximum SUV (SUV(max)) nor 18F-FLT SUV(max) correlated with Ki-67 expression in the linear regression analysis. CONCLUSION: In this study, uptake of 18F-FDG in esophageal cancer is significantly higher compared with 18F-FLT uptake. 18F-FLT scans show more false-negative findings and fewer false-positive findings than do 18F-FDG scans. Uptake of 18F-FDG or 18F-FLT did not correlate with proliferation.     

18F-FLT与18F-FDG PET/CT不同判断方法鉴别肺良恶性肿瘤诊断效能的比较

目的 通过分析多中心临床研究病例,比较18F-脱氧胸腺嘧啶核苷(FIT)、18F-脱氧葡萄糖(FDG)PET/CT显像诊断肺恶性肿瘤的效能.方法 通过随机、盲法、前瞻性的多中心研究,获得以病理检查或临床随访结果确定诊断的55例肺结节患者,均同时行18F-FDG和18F-FLT PET/CT检查.应用受试者工作特征(ROC)曲线分析方法,分别计算病灶最大标准摄取值(SUVmax)、视觉评分、集体盲法阅片等方法的曲线下面积,比较不同检查方法、不同诊断方法的诊断效能.结果 目测经病理或随访检查确诊的16例肺癌、16例肺结核、23例肺炎或其他类型疾病患者,18F-FDG和18F-FLT SUVmax、视觉评分法、集体阅片法曲线下面积分别为0.780±0.065,0.768±0.063,0.803±0.068和0.828±0.058,0.709±0.082,0.763±0.072.通过约登指数选择18F-FDG SUVmax≥6.0,18F-FLT SUVmax≥2.4为良恶性诊断阈值,18F-FDG和18F-FLT单独SUVmax法和盲法集体阅片对肺恶性肿瘤诊断的灵敏度、特异性和准确性分别为75.0%(12/16)、64.1%(25/39)、67.3%(37/55),81.3%(13/16)、82.1%(32/39)、81.8%(45/55)和81.3%(13/16)、87.2%(34/39)、85.5%(47/55).结论 18F-FDG、18F-FLT单独诊断肺恶性肿瘤的效能均为中等;18F-FLT SUVmax法优于18F-FDG;18F-FDG和18F-FLT图像结合判读可获得最佳诊断效能.     

18F-FLT PET for visualization of laryngeal cancer: comparison with 18F-FDG PET.

The feasibility of (18)F-3'-fluoro-3'-deoxy-L-thymidine PET (FLT PET) for detecting laryngeal cancer was investigated and compared with (18)F-FDG PET. METHODS: Eleven patients diagnosed with or strongly suspected of having recurrent laryngeal cancer and 10 patients with histologically proven primary laryngeal cancer underwent attenuation-corrected (18)F-FLT PET imaging 60 min after injection of a median of 213 MBq (range, 175-400 MBq) (18)F-FLT and attenuation-corrected (18)F-FDG PET imaging 90 min after injection of a median of 340 MBq (range, 165-650 MBq) (18)F-FDG. All patients were staged by endoscopy and CT according to the Union Internationale Contre la Cancer TNM staging system. All patients underwent biopsy of the laryngeal area after imaging. Lesions seen on (18)F-FDG PET and (18)F-FLT PET were compared with histopathologic results. Mean SUVs, maximum SUVs, and tumor-to-nontumor (TNT) ratios were calculated for (18)F-FLT and (18)F-FDG. Wilcoxon nonparametric testing was used for comparison of (18)F-FDG with (18)F-FLT uptake. The Spearman correlation coefficient was used to correlate mean SUVs, maximum SUVs, and TNT ratios of (18)F-FDG PET and (18)F-FLT PET. Two-tailed P values < 0.05 were considered significant. RESULTS: (18)F-FDG PET and (18)F-FLT PET detected laryngeal cancer correctly in 15 of 17 patients. One lesion judged as positive on (18)F-FDG PET turned out to be normal tissue. Of 2 lesions judged as positive on (18)F-FLT PET, 1 turned out to be inflammation and the other to be normal tissue. Maximum SUVs were 3.3 (range, 1.9-8.5) for (18)F-FDG and 1.6 (range, 1.0-5.7) for (18)F-FLT (P < 0.001). Mean SUVs were 2.7 (range, 1.5-6.5) for (18)F-FDG and 1.2 (range, 0.8-3.8) for (18)F-FLT (P < 0.001). TNT was 1.9 (range, 1.3-4.7) for (18)F-FDG and 1.5 (range, 1.1-3.5) for (18)F-FLT (P < 0.05). CONCLUSION: The numbers of laryngeal cancers detected with (18)F-FLT PET and (18)F-FDG PET were equal. In laryngeal cancer, the uptake of (18)F-FDG is higher than that of (18)F-FLT.     

Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG.

Recently, the thymidine analog 3'-deoxy-3'-(18)F-fluorothymidine (FLT) was suggested for imaging tumoral proliferation. In this prospective study, we examined whether (18)F-FLT better determines proliferative activity in newly diagnosed lung nodules than does (18)F-FDG. METHODS: Twenty-six patients with pulmonary nodules on chest CT were examined with PET and the tracers (18)F-FDG and (18)F-FLT. Tumoral uptake was determined by calculation of standardized uptake value (SUV). Within 2 wk, patients underwent resective surgery or had core biopsy. Proliferative activity was estimated by counting nuclei stained with the Ki-67-specific monoclonal antibody MIB-1 per total number of nuclei in representative tissue specimens. The correlation between the percentage of proliferating cells and the SUVs for (18)F-FLT and (18)F-FDG was determined using linear regression analysis. RESULTS: Eighteen patients had malignant tumors (13 with non-small cell lung cancer [NSCLC], 1 with small cell lung cancer, and 4 with pulmonary metastases from extrapulmonary tumors); 8 had benign lesions. In all visible lesions, mean (18)F-FDG uptake was 4.1 (median, 4.4; SD, 3.0; range, 1.0-10.6), and mean (18)F-FLT uptake was 1.8 (median, 1.2; SD, 2.0; range, 0.8-6.4). Statistical analysis revealed a significantly higher uptake of (18)F-FDG than of (18)F-FLT (Mann-Whitney U test, P < 0.05). (18)F-FLT SUV correlated better with proliferation index (P < 0.0001; r = 0.92) than did (18)F-FDG SUV (P < 0.001; r = 0.59). With the exception of 1 carcinoma in situ, all malignant tumors showed increased (18)F-FDG PET uptake. (18)F-FLT PET was false-negative in the carcinoma in situ, in another NSCLC with a low proliferation index, and in a patient with lung metastases from colorectal cancer. Increased (18)F-FLT uptake was related exclusively to malignant tumors. By contrast, (18)F-FDG PET was false-positive in 4 of 8 patients with benign lesions. CONCLUSION: (18)F-FLT uptake correlates better with proliferation of lung tumors than does uptake of (18)F-FDG and might be more useful as a selective biomarker for tumor proliferation.     

Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG.

3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a recently developed PET tracer to image tumor cell proliferation. We characterized (18)F-FLT PET of brain gliomas and compared (18)F-FLT with (18)F-FDG PET in side-by-side studies of the same patients. METHODS: Twenty-five patients with newly diagnosed or previously treated glioma underwent PET with (18)F-FLT and (18)F-FDG on consecutive days. Three stable patients in long-term remission were included as negative control subjects. Tracer kinetics in normal brain and tumor were measured. Uptake of (18)F-FLT and (18)F-FDG was quantified by the standardized uptake value (SUV) and the tumor-to-normal tissue (T/N) ratio. The accuracy of (18)F-FLT and (18)F-FDG PET in evaluating newly diagnosed and recurrent gliomas was compared. More than half of the patients underwent resection after the PET study and correlations between PET uptake and the Ki-67 proliferation index were examined. Patients were monitored for a mean of 15.4 mo (range, 12-20 mo). The predictive power of PET for tumor progression and survival was analyzed using Kaplan-Meier statistics. RESULTS: (18)F-FLT uptake in tumors was rapid, peaking at 5-10 min after injection and remaining stable up to 75 min. Hence, a 30-min scan beginning at 5 min after injection was sufficient for imaging. (18)F-FLT visualized all high-grade (grade III or IV) tumors. Grade II tumor did not show appreciable (18)F-FLT uptake and neither did the stable lesions. The absolute uptake of (18)F-FLT was low (maximum-pixel SUV [SUV(max)], 1.33) but image contrast was better than with (18)F-FDG (T/N ratio, 3.85 vs. 1.49). (18)F-FDG PET studies were negative in 5 patients with recurrent high-grade glioma who subsequently suffered tumor progression within 1-3 mo. (18)F-FLT SUV(max) correlated more strongly with Ki-67 index (r = 0.84; P < 0.0001) than (18)F-FDG SUV(max) (r = 0.51; P = 0.07). (18)F-FLT uptake also had more significant predictive power with respect to tumor progression and survival (P = 0.0005 and P = 0.001, respectively). CONCLUSION: Thirty-minute (18)F-FLT PET 5 min after injection was more sensitive than (18)F-FDG to image recurrent high-grade tumors, correlated better with Ki-67 values, and was a more powerful predictor of tumor progression and survival. Thus, (18)F-FLT appears to be a promising tracer as a surrogate marker of proliferation in high-grade gliomas.     

Imaging gastric cancer with PET and the radiotracers 18F-FLT and 18F-FDG: a comparative analysis.

In this pilot study, we evaluated 3'-deoxy-3'-(18)F-fluorothymidine (FLT) PET for the detection of gastric cancer and compared the diagnostic accuracy with that of (18)F-FDG PET. METHODS: Forty-five patients (31 male and 14 female) with histologically proven locally advanced gastric cancer underwent attenuation-corrected whole-body (18)F-FLT PET and (18)F-FDG PET/CT (low-dose CT). (18)F-FLT emission images were acquired on a full-ring PET scanner 45 min after the injection of 270-340 MBq of (18)F-FLT. (18)F-FDG PET/CT was performed 60 min after the injection of 300-370 MBq of (18)F-FDG. Mean standardized uptake values for (18)F-FLT and (18)F-FDG were calculated using circular ROIs (diameter, 1.5 cm) in the primary tumor manifestation site, in a reference segment of the liver, and in the bone marrow and were compared on a lesion-by-lesion basis. RESULTS: According to the Lauren classification, 15 tumors (33%) were of the intestinal subtype and 30 (67%) of the nonintestinal subtype. (18)F-FLT PET images showed high contrast for the primary tumor and proliferating bone marrow. In all patients (45/45), focal (18)F-FLT uptake could be detected in the primary tumor. In contrast, 14 primary tumors were negative for (18)F-FDG uptake, with lesional (18)F-FDG uptake lower than or similar to background activity. The mean standardized uptake value for (18)F-FLT in malignant primaries was 6.0 +/- 2.5 (range, 2.4-12.7). In the subgroup of (18)F-FDG-positive patients, the mean value for (18)F-FDG was 8.4 +/- 4.1 (range, 3.8/19.0), versus 6.8 +/- 2.6 for (18)F-FLT (Wilcoxon test: P = 0.03). Comparison of mean (18)F-FLT and (18)F-FDG uptake in tumors with signet ring cells revealed no statistically significant difference between the tracers (6.2 +/- 2.1 for (18)F-FLT vs. 6.4 +/- 2.8 for (18)F-FDG; Wilcoxon test: P = 0.94). CONCLUSION: The results of this study indicate that imaging gastric cancer with the proliferation marker (18)F-FLT is feasible. (18)F-FLT PET was more sensitive than (18)F-FDG PET, especially in tumors frequently presenting without or with low (18)F-FDG uptake, and may improve early evaluation of response to neoadjuvant treatment.     

~(18)F-FDG和~(18)F-FLT PET显像SUV在肺结块诊断中的价值

目的:探讨18F-氟氏脱氧葡萄糖(18F-FDG)和18F-氟氏胸腺嘧啶(18F-FLT)PET显像诊断肺结块的影响因素,以提高PET/CT对肺结块的诊断价值。方法:选择肺结块患者55例为研究对象,其中28例为肺内孤立结块,其余为2～3个结块,结块大小0.6～11.0cm。所有患者均行肺部18 F-FDG和18 F-FLT PET/CT检查,检查结果按不同性别、年龄、结块大小及病理类型进行分组,以各组18F-FDG和18F-FLT显像标准摄取值(SUV)的均数为界定标准,分析SUV与肺结块患者的性别、年龄、结块大小及病理类型等相互关系。结果:55例肺结块患者,不同性别、年龄、结块大小患者的18 F-FDG和18F-FLT显像SUV差异均无统计学意义(P>0.05),不同病理类型患者的18 F-FDG显像SUV差异无统计学意义(P>0.05),而不同病理类型患者的18F-FLT显像SUV差异有统计学意义(P<0.05)。结论:肺结块患者结块的病理类型是影响18F-FLT显像SUV的重要因素,18F-FLT PET/CT显像SUV鉴别诊断肺结块良恶性具有重要的价值和意义。     

18F-FDG和18F-FLT PET/CT在肺部良恶性肿瘤鉴别诊断中的价值

目的:分析18F-FDG(18F-脱氧葡萄糖)和18F-FLT(18F-胸腺嘧啶)两种显像剂的PET/CT检查在肺部肿瘤中的不同影像学表现,提高PET/CT在肺部良恶性肿瘤鉴别诊断中价值,从而为临床治疗方案的选择提供可靠依据。方法:收集肺肿瘤患者55例为研究对象,其中男性33例,女性22例,年龄17～82岁,28例为肺内孤立肿块,其余为2～3个肿块,肿块大小0.6～11.0cm,所有患者均行肺部18 F-FDG和18 F-FLT PET/CT检查,分析18 F-FDG和18 F-FLT标准摄取值(SUV)与肺肿瘤患者的年龄、肿块大小及病理类型等相互关系和统计学意义。结果:18 F-FDG和18 F-FLT PET/CT的SUV与肺肿瘤患者的年龄、肿块大小均无统计学差异(P>0.05),18 F-FDG PET/CT的SUV与患者的病理类型亦无统计学差异(P>0.05),而18F-FLT PET/CT的SUV与患者的病理类型有统计学差异(P<0.05)。结论:肺肿瘤患者的肿块病理类型是影响18F-FLT PET/CT的SUV的重要因素,18F-FLT PET/CT的SUV在肺部良恶性肿瘤鉴别诊断中具有重要的价值。     

The value of SUV in 18F-FDG and 18F-FLT PET imaging for diagnosing pulmonary nodules

目的:探讨18F-氟氏脱氧葡萄糖(18F-FDG)和18F-氟氏胸腺嘧啶(18F-FLT)PET显像诊断肺结块的影响因素,以提高PET/CT对肺结块的诊断价值.方法:选择肺结块患者55例为研究对象,其中28例为肺内孤立结块,其余为2～3个结块,结块大小0.6～11.0 cm.所有患者均行肺部18F-FDG和18F-FLT PET/CT检查.检查结果按不同性别、年龄、结块大小及病理类型进行分组,以各组18F-FDG和18F-FLT显像标准摄取值(SUV)的均数为界定标准.分析SUV与肺结块患者的性别、年龄、结块大小及病理类型等相互关系.结果:55例肺结块患者,不同性别、年龄、结块大小患者的18F-FDG和18F-FLT显像SUV差异均无统计学意义(P>0.05),不同病理类型患者的18F-FDG显像SUV差异无统计学意义(P>0.05),而不同病理类型患者的18F-FLT显像SUV差异有统计学意义(P<0.05).结论:肺结块患者结块的病理类型是影响18F-FLT显像SUV的重要因素,18F-FLT PET/CT显像SUV鉴别诊断肺结块良恶性具有重要的价值和意义.     

Autoradiographic and small-animal PET comparisons between (18)F-FMISO, (18)F-FDG, (18)F-FLT and the hypoxic selective (64)Cu-ATSM in a rodent model of cancer

INTRODUCTION: Copper(II)-diacetyl-bis(N(4)-methylthiosemicarbazone), or Cu-ATSM, a hypoxia imaging agent, has been shown to be predictive of response to traditional cancer therapies in patients with a wide range of tumors. It is known that the environment of the tumor results in a myriad of physiological consequences, including hypoxia, alterations in metabolism and proliferation. In an effort to better characterize the relationships between Cu-ATSM and other prominent radiopharmaceuticals, this current study was undertaken to compare the regional distribution of (64)Cu-ATSM with [(18)F]fluoromisonidazole ((18)F-FMISO), [(18)F]fluoro-2-deoxy-d-glucose ((18)F-FDG) and [(18)F]fluorothymidine ((18)F-FLT) in 9L tumors. METHODS: Taking advantage of the different half-life of (18)F (t(1/2)=110 min) in comparison to (64)Cu (t(1/2)=12.7 h), we undertook a dual-tracer autoradiography study in 9L tumors. Four groups were examined: (a) (18)F-FMISO, 2 h postinjection (p.i.) and (64)Cu-ATSM, 10 min p.i.; (b) (18)F-FMISO, 2 h p.i. and (64)Cu-ATSM, 24 h p.i.; (c) (18)F-FDG, 1 h p.i. and (64)Cu-ATSM, 10 min p.i.; and (d) (18)F-FLT, 1 h p.i. and (64)Cu-ATSM, 10 min p.i. Small-animal PET imaging was performed in 9L tumor-bearing rats with imaging on concurrent days comparing (64)Cu-ATSM with (18)F-FMISO and (18)F-FLT. RESULTS: It was shown that the regional distribution of (18)F-FMISO and (64)Cu-ATSM showed an excellent correlation when the (64)Cu-ATSM had been allowed to distribute for either 10 min (R(2)=.84) or 24 h (R(2)=.86). The regional comparisons between (64)Cu-ATSM (10 min) and (18)F-FDG (1 h) resulted in a very poor correlation (R(2)=.08) between the regional uptake of the two agents. The comparison between (18)F-FLT and (64)Cu-ATSM showed a strong relationship (R(2)=.83) between the two tracers. The small-animal PET images for the distribution comparisons between (64)Cu-ATSM and (18)F-FMISO and (18)F-FLT were in agreement with the data generated from the autoradiography studies. CONCLUSIONS: The data show that it is important to remember that a number of different metabolic situations can exist when considering the relationship between regions of high glucose uptake, proliferation and hypoxia.     

Gene expression patterns and tumor uptake of 18F-FDG, 18F-FLT, and 18F-FEC in PET/MRI of an orthotopic mouse xenotransplantation model of pancreatic cancer

Our aim was to use PET/MRI to evaluate and compare the uptake of 18F-FDG, 3-deoxy-3-18F-fluorothymidine (18F-FLT), and 18F-fluorethylcholine (18F-FEC) in human pancreatic tumor cell lines after xenotransplantation into SCID mice and to correlate tumor uptake with gene expression of membrane transporters and rate-limiting enzymes for tracer uptake and tracer retention. METHODS: Four weeks after orthotopic inoculation of human pancreatic carcinoma cells (PancTuI, Colo357, and BxPC3) into SCID mice, combined imaging was performed with a small-animal PET scanner and a 3-T MRI scanner using a dedicated mouse coil. Tumor-to-liver uptake ratios (TLRs) of the tracers were compared with gene expression profiles of the tumor cell lines and both normal pancreatic tissue and pancreatic tumor tissue based on gene microarray analysis and quantitative polymerase chain reaction. RESULTS: 18F-FLT showed the highest tumor uptake, with a mean TLR of 2.3, allowing correct visualization of all 12 pancreatic tumors. 18F-FDG detected only 4 of 8 tumors and had low uptake in tumors, with a mean TLR of 1.1 in visible tumors. 18F-FEC did not show any tumor uptake. Gene array analysis revealed that both hexokinase 1 as the rate-limiting enzyme for 18F-FDG trapping and pancreas-specific glucose transporter 2 were significantly downregulated whereas thymidine kinase 1, responsible for 18F-FLT trapping, was significantly upregulated in the tumor cell lines, compared with normal pancreatic duct cells and pancreatic tumor tissue. Relevant genes involved in the uptake of 18F-FEC were predominantly unaffected or downregulated in the tumor cell lines. CONCLUSION: In comparison to 18F-FDG and 18F-FEC, 18F-FLT was the PET tracer with the highest and most consistent uptake in various human pancreatic tumor cell lines in SCID mice. The imaging results could be explained by gene expression patterns of membrane transporters and enzymes for tracer uptake and retention as measured by gene array analysis and quantitative polymerase chain reaction in the respective cell lines. Thus, standard molecular techniques provided the basis to help explain model-specific tracer uptake patterns in xenotransplanted human tumor cell lines in mice as observed by PET.     

Dual time point 18F-FDG PET imaging for differentiating malignant from inflammatory processes.

The aim of this study was to investigate the difference in the rates of FDG uptake between malignant and inflammatory cells and processes. METHODS: In vitro studies: (18)F-FDG uptake by different tumor cell lines (human mesothelioma [REN]; rat mesothelioma [II45]; mice melanoma [B18F10]; mice mesothelioma [AB12]; human myeloma [GM1500]; and human ovarian cancer [SKOV3]) and peripheral blood mononuclear cells isolated from 8 healthy human volunteers was measured 20 and 60 min after FDG was added into growth medium. Animal studies: II45 cells were implanted into the left flank of rats (n = 5) and a focal inflammatory reaction (mechanical irritation) was generated in the right flank. PET images at 45 and 90 min after injection of FDG were obtained and standardized uptake values (SUVs) were determined. Patient studies: Seventy-six patients who had dual time FDG PET scans were retrospectively analyzed. All results were expressed as the percentage change in SUV of the later time image from that of the earlier time (mean +/- SD). RESULTS: In vitro studies: Except for the SKOV3 cell line, which had only minimally increased FDG uptake (+10% +/- 26%; P > 0.3), all other tumor cell lines tested showed significantly increased FDG uptake over time (GM1500, +59% +/- 19%; B18F10, +81% +/- 15%; AB12, 93% +/- 21%; II45, +161% +/- 21%; REN, +198% +/- 48%; P < 0.01 for all). By contrast, FDG uptake in mononuclear cells was decreased in 7 of 8 donors. Animal studies: SUVs of tumors from 90-min images were significantly higher than those from 45-min images (+18% +/- 8%; P < 0.01), whereas the SUVs of inflammatory lesions decreased over time (-17% +/- 13% of the early images; P < 0.05). Clinical studies: The SUVs of delayed images from the known malignant lesions compared with those of earlier scans increased over time (+19.18% +/- 9.58%; n = 31; P < 0.001; 95% confidence interval, 15.8%-22.6%). By contrast, the SUVs of benign lung nodules decreased slightly over time (-6.3% +/- 8.1%; n = 12; P < 0.05; 95% confidence interval, -10.9% to -1.7%). The SUV of inflammatory lesions caused by radiation therapy (+1.16% +/- 7.23%; n = 8; P > 0.05; 95% confidence interval, -3.9%-6.2%) and the lesions of painful lower limb prostheses (+4.03% +/- 11.32%; n = 25; P > 0.05; 95% confidence interval, -0.4%-8.5%) remained stable over time. CONCLUSION: These preliminary data show that dual time imaging appears to be useful in distinguishing malignant from benign lesions. Further research is necessary to confirm these results.     

18F-FDG和18F-FLT PET/CT不同诊断方法在肺部单发结节中的临床价值分析

目的：探讨18F-FDG和18F-胸腺嘧啶核苷（FLT）PET/CT不同的诊断方法对肺部单发结节的诊断价值。方法对40例发现肺部单发结节的患者行18F-FDG和18F-FLT PET/CT显像,所有病例均经病理或密切随访确诊,应用受试者工作特征（ROC）曲线比较18F-FDG SUVmax、18F-FLT SUVmax、18F-FLT SUVmax/同层面椎体SUVmax对肺部恶性肿瘤的诊断价值;18F-FDG和18F-FLT PET/CT两种显像结果均行视觉分析和半定量分析,比较不同诊断方法的诊断效能。结果18F-FDG SUVmax、18F-FLT SUVmax及18F-FLT SUVmax/同层面椎体SUVmaxROC曲线下面积分别为0.687、0.821和0.817。以18F-FDG SUVmax>2.5、18F-FLT SUVmax>2.0为恶性诊断标准、18F-FDG PET/CT视觉分析评分法、18F-FLT PET/CT视觉分析评分法4种方法诊断肺癌的灵敏度、特异度和准确率分别为88.2%、73.9%和80.0%;58.8%、82.6%和72.5%;94.1%、91.3%和92.5%;88.2%、65.2%和75.0%。结论18F-FLT SUVmax及18F-FLT SUVmax/同层面椎体SUVmax单独诊断肺部恶性肿瘤的价值较18F-FDG SUVmax高,且前两者可替换使用。18F-FDG PET/CT视觉评分法在肺部单发结节良恶性的诊断中效能最佳。     

18F-FLT和18F-FDG PET/CT对胸段食管癌淋巴结分期诊断的对比研究

目的 评价18F-脱氧胸苷（FLT）PET/CT对未经治疗的胸段食管癌淋巴结分期诊断的价值,并与18F-脱氧葡萄糖（FDG）PET/CT进行比较.方法 选择22例拟行手术治疗的胸段食管癌患者,术前行双显像剂PET/CT检查及淋巴结分期诊断,术后以病理学诊断为＂金标准＂,比较18F-FLT和18F-FDG PET/CT对胸段食管癌淋巴结分期的灵敏度、特异性、准确性、阳性预测值和阴性预测值.应用SPSS 13.0软件进行x2检验.结果 患者均行食管癌切除和淋巴结清扫术,病理检查结果显示16例患者存在淋巴结转移,N0期7例,N1期15例,M1a期6例（其中1例为N0M1a,另外5例为N1M1a）,全组均无M1b期.共检出424枚淋巴结,其中47枚为转移淋巴结.18F-FDG PET/CT诊断呈假阳性的淋巴结14枚,而18F-FLT诊断呈假阳性的淋巴结为3枚;18F-FDG假阴性的淋巴结8枚,18F-FLT假阴性的淋巴结12枚.18F-FLT PET/CT的诊断灵敏度、特异性、准确性、阴性预测值和阳性预测值分别为74.47%（35/47）、99.20%（374/377）、96.46%（409/424）、96.89%（374/386）和92.11%（35/38）,18F-FDG分别为82.98%（39/47）、96.29%（363/377）、94.81%（402/424）、97.84%（363/371）和73.58%（39/53）;两者比较的x2值分别为0.572,6.018,1.017,0.348,3.852,P值分别＞0.05,＜0.05、＞0.05、＞0.05和＞0.05.结论 18F-FLT对食管癌区域淋巴结的诊断灵敏度与18F-FDG显像接近,特异性高于18F-FDG,但仍存在一定的局限性.     

Comparison of sigma-ligands and metabolic PET tracers for differentiating tumor from inflammation.

Novel radiopharmaceuticals for the detection of tumors and their metastases may be of clinical interest if they are more tumor selective than (18)F-FDG. Increased glucose metabolism of inflammatory tissues is the main source of false-positive (18)F-FDG PET findings in oncology. METHODS: We compared the biodistribution of 4 PET tracers (2 sigma-receptor ligands, (11)C-choline, and (11)C-methionine) with previously published biodistribution data of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) and of (18)F-FDG in the same animal model. The model consisted of male Wistar rats that bore tumors (C6 rat glioma in the right shoulder) and also had sterile inflammation in the left calf muscle (induced by injection of 0.1 mL of turpentine). Twenty-four hours after turpentine injection, the rats received an intravenous bolus of PET tracer (approximately 30 MBq in the case of (18)F and 74 MBq for (11)C). RESULTS: (18)F-FDG showed the highest tumor-to-muscle ratio of all radiopharmaceuticals (13.2 +/- 3.0, mean +/- SD), followed at a large distance by the sigma-1 ligand (11)C-SA4503 (5.1 +/- 1.7), (18)F-FLT (3.8 +/- 1.3), the non-subtype-selective sigma-ligand (18)F-FE-SA5845 (3.3 +/- 1.5), (11)C-choline (3.1 +/- 0.4), and (11)C-methionine (2.8 +/- 0.3). sigma-Ligands and (18)F-FLT were relatively tumor selective ((18)F-FE-SA5845, greater than 30-fold; (11)C-SA4503 and (18)F-FLT, greater than 10-fold). The tumor selectivity of (11)C-methionine was only slightly better than that of (18)F-FDG. (11)C-Choline showed equal uptake in tumor and inflammation. All tracers were avidly taken up by proliferative tissue (small intestine, bone marrow). High physiologic uptake of some compounds was observed in brain, heart, lung, pancreas, spleen, and salivary gland. CONCLUSION: sigma-Ligands and (18)F-FLT were more tumor selective than (18)F-FDG, (11)C-choline, or (11)C-methionine in our animal model. However, these novel radiopharmaceuticals were less sensitive than were the established oncologic tracers.     

Dynamic whole-body 18F-FDG PET for differentiating abnormal lesions from physiological uptake

European Journal of Nuclear Medicine and Molecular Imaging - Serial assessment of visual change in 18F-FDG uptake on whole-body 18F-FDG PET imaging was performed to differentiate pathological...