Treatment monitoring by 18F-FDG PET/CT in patients with sarcomas: interobserver variability of quantitative parameters in treatment-induced changes in histopathologically responding and nonresponding tumors

Measurements of tumor glucose use by (18)F-FDG PET need to be standardized within and across institutions. Various parameters are used for measuring changes in tumor glucose metabolic activity with (18)F-FDG PET in response to cancer treatments. However, it is unknown which of these provide the lowest variability between observers. Knowledge of the interobserver variability of quantitative parameters is important in sarcomas as these tumors are frequently large and demonstrate heterogeneous (18)F-FDG uptake. METHODS: A total of 33 patients (16 men, 17 women; mean age, 47 +/- 18 y) with high-grade sarcomas underwent (18)F-FDG PET/CT scans before and after neoadjuvant chemotherapy. Two independent investigators measured the following parameters on the pretreatment and posttreatment scans: maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), mean SUV (SUVmean), SUVmean in an automatically defined volume (SUVauto), and tumor-to-background ratio (TBR). The variability of the different parameters was compared by concordance correlation coefficient (CCC), variability effect coefficient, and Bland-Altman plots. RESULTS: Baseline SUVmax, SUVpeak, SUVmean, SUVauto, and TBR averaged 10.36, 7.78, 4.13, and 6.22 g/mL and 14.67, respectively. They decreased to 5.36, 3.80, 1.79, and 3.25 g/mL and 6.62, respectively, after treatment. SUVmax, SUVpeak, and SUVauto measurements and their changes were reproducible (CCC > or = 0.98). However, SUVauto poorly differentiated between responding and nonresponding tumors. The high intratumoral heterogeneity of (18)F-FDG resulted in frequent failure of the thresholding algorithm, which necessitated manual corrections that in turn resulted in a higher interobserver variability of SUVmean (CCCs for follow-up and change were 0.96 and 0.91, respectively; P < 0.005). TBRs also showed a significantly higher variability than did SUVpeak (CCCs for follow-up and change were 0.94 and 0.86, respectively; P < 0.005). CONCLUSION: SUVmax and SUVpeak provided the most robust measurements of tumor glucose metabolism in sarcomas. Delineation of the whole-tumor volume by semiautomatic thresholding did not decrease the variability of SUV measurements. TBRs were significantly more observer-dependent than were absolute SUVs. These findings should be considered for standardization of clinical (18)F-FDG PET/CT trials.     

A threshold method to improve standardized uptake value reproducibility

Although standardized uptake values (SUV) are widely used to quantify the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours, there are systematic differences in the way this index is applied by different investigators. The aims of this study were to compare the effects of using maximum or mean region counts in the calculation of SUV and to investigate an alternative technique based on a fixed fraction of the maximum counts. Simulated PET projections of the thorax were generated together with spherical lesions that varied in diameter from 1.6 to 4.8 cm with uptake values of 2, 4 and 8. The lesion SUVs were determined using either the maximum (SUVmax) or mean count (SUVmean) values found in regions circumscribing the lesion. In addition, average values were calculated that only included region pixels that exceeded a selected fraction of maximum value (SUV0.6max or SUV0.75max). These methods were also applied to six clinical 18F-FDG PET studies with a total of 12 lesions. The SUVs for these lesions were determined independently by four observers. Decreases with respect to SUVmax of 57%, 23% and 14% were found for SUVmean, SUV0.6max and SUV0.75max approaches respectively in the simulation study. The variation in SUVmean with region size was 35%, while the SUV0.6max and SUV0.75max was less than 3%. Similar results were obtained for the clinical data. We conclude that the proposed technique produces SUVs that are essentially independent of lesion region size and shape. It is expected that this will provide a more stable and reliable result than current approaches.     

^18F-FDG PET/CT不同重建算法对肺结节SUV的影响

目的 比较18 F-脱氧葡萄糖(FDG) PET/CT的4种重建算法对肺结节标准摄取值(SUV)的影响.方法 回顾性收集2018年2月至2019年7月在山西医科大学第一医院行^18F-FDGPET/CT检查的46例实性肺结节患者[男27例,女19例,中位年龄66(44~82)岁]的PET/CT图像,采用有序子集最大期望值迭代法(OSEM)、OSEM+飞行时间(TOF)、OSEM+TOF+点扩散函数(PSF)及正则化算法(BSREM)进行图像重建(方法依次以G1~G4表示),通过视觉和半定量方法分析肺结节及背景参数.根据肺窗所测结节直径,分为小结节(直径≤10 mm)和大结节(10 mm<直径≤30 mm).行Kruskal-Wallis秩和检验及Bonferroni法分析不同算法间SUV的差异,行Spearman相关分析探讨SUV变化率(%△SUV)与结节直径的相关性,行受试者工作特征(ROC)曲线分析探讨SUV对肺结节良恶性的诊断效能.结果 共114个结节,大结节55个,小结节59个.在视觉分析中,G4较G1 ~ G3的小结节视觉检出率分别提高了55.93%(33/59)、44.07% (26/59)和20.34% (12/59).在114个肺结节中,最大SUV(SUVmax)、平均SUV(SUVmean)在不同算法间比较差异有统计学意义(中位SUVmax:2.65~5.29,中位SUVmean:2.05~ 2.99;H值:20.628和17.749,均P<0.001),G4对G1的SUVmax(中位数分别为5.29和2.65)和SUVmean(中位数分别为2.99和2.05)有明显提升(均P<0.001).%△SUVmax(中位数:4.45%~52.96%)、%△SUVmean(中位数:1.69% ~47.56%)与结节直径呈负相关[9.75(6.20,16.58) mm;rs值:-0.371^-0.354、-0.371 ^-0.320,均P<0.001].在59个小结节中,G4对G1的SUVmax(中位数分别为4.05和2.14)有明显提升(H=18.327,P<0.001),G4对G1和G3的SUVmean(中位数分别为2.31、1.26和1.53)有提升作用(H=16.808,均P<0.05).在55个大结节中,SUV在不同算法间的差异无统计学意义(H值:0.812~7.290,均P>0.05).G1~G4的SUVmax诊断良恶性的最佳截断值分别为4.335、5.185、5.410、5.745,曲线下面积(AUC)分别为0.747、0.699、0.756和0.778,四者的SUVmean及SUVpeak最佳截断值对应的AUC也显示出类似趋势.结论 在4种重建算法中,BSREM可明显提高图像质量和直径10 mm以下肺结节的SUVmax及SUVmean,其SUV良恶性诊断阈值应适当上调.     

Dual time point 18F-FDG PET for the evaluation of pulmonary nodules.

18F-FDG PET has reached widespread application in the assessment of pulmonary nodules. This study compares the diagnostic accuracy of standard 18F-FDG PET scanning with those of dual time point 18F-FDG PET scanning. METHODS: Thirty-six patients (21 women, 15 men; mean age, 67 y; range, 36-88 y) with 38 known or suspected malignant pulmonary nodules underwent PET of the thorax at 2 time points: scan 1 at 70 min (range, 56-110 min) and scan 2 at 123 min (range, 100-163 min) after the intravenous injection of 2.5 MBq 18F-FDG per kilogram of body weight. All scanning was performed on a dedicated C-PET scanner. The mean interval between the scans was 56 min (range, 49-64 min). Regions of interest were overlaid onto each fully corrected image in the areas of the radiographically known lung densities. The standardized uptake values (SUVs) were calculated for both time points. RESULTS: Surgical pathology and follow-up revealed 19 patients with 20 malignant tumors, whereas 16 patients had benign lesions. The tumor SUVs (mean +/- SD) were 3.66 +/- 1.95 (scan 1) and 4.43 +/- 2.43 (scan 2) (20.5% +/- 8.1% increase; P < 0.01). Four of 20 malignant tumors had SUVs of <2.5 on scan 1 (range, 1.12-1.69). Benign lesions had SUVs of 1.14 +/- 0.64 (scan 1) and 1.11 +/- 0.70 (scan 2) (P = not significant). Standard PET scanning (single time point) with a threshold SUV of 2.5 (at time point 1) reached a sensitivity of 80% and a specificity of 94%; dual time point scanning with a threshold value of 10% increase between scan 1 and scan 2 reached a sensitivity of 100% with a specificity of 89%. CONCLUSION: Dual time point 18F-FDG PET results in a very high sensitivity and specificity for detection of malignant lung tumors.     

Relationship between 18F-FDG uptake and breast density in women with normal breast tissue.

Breast density affects the mammographic detectability of breast cancer. The study aimed to evaluate the impact of breast density on the (18)F-FDG uptake of normal breast tissue. METHODS: The study population consisted of 45 women (median age, 54 y; age range, 42-77 y). All underwent whole-body (18)F-FDG PET for various indications other than breast cancer, and all underwent mammography within a mean of 6.6 +/- 4.9 mo of PET. On the basis of mammographic findings, breasts were categorized as extremely dense, heterogeneously dense, primarily fatty, or entirely fatty. Regions of interest were drawn on every PET image in which breast tissue was visualized. Average and peak standardized uptake values (SUVs) were calculated for the left and right breasts. RESULTS: Mammography showed that 20 of the 45 women had heterogeneously dense breasts, 1 had extremely dense breasts, 20 had primarily fatty breasts, and 4 had entirely fatty breasts. In dense breasts, the average SUV was 0.39 +/- 0.05 (right breast) and 0.36 +/- 0.07 (left breast) and the peak SUV was 0.93 +/- 0.16 and 0.89 +/- 0.18, respectively. The average and peak SUVs were significantly lower for primarily fatty breasts than for dense breasts (P < 0.01). Peak and average SUVs of entirely fatty breasts also differed significantly from peak and average SUVs of dense and primarily fatty breasts (P < 0.01). The impact of hormonal status on SUV was significant but less than the impact of breast density. No significant relationship between average SUV or peak SUV and age or serum glucose level was observed. CONCLUSION: Breast density and hormonal status affect the uptake of (18)F-FDG. Dense breasts exhibit, on average, significantly higher (18)F-FDG uptake than do nondense breasts. However, the highest peak SUV observed in dense breasts was 1.39, which is well below the SUV of 2.5 commonly used as a cutoff between benign and malignant tissue. Therefore, breast density is unlikely to affect the ability of (18)F-FDG PET to discriminate between benign and malignant breast lesions.     

Early 18F-FDG PET for prediction of prognosis in patients with diffuse large B-cell lymphoma: SUV-based assessment versus visual analysis.

The purpose of this study was to assess the prognostic value of early (18)F-FDG PET using standardized uptake value (SUV) compared with visual analysis in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Ninety-two patients with newly diagnosed DLBCL underwent (18)F-FDG PET prospectively before and after 2 cycles of chemotherapy (at midtherapy). Maximum SUV (SUVmax) and mean SUV (SUVmean) normalized to body weight and body surface area, as well as tumor-to-normal ratios, were computed on the most intense uptake areas. The SUVs, tumor-to-normal ratios, and their changes over time were compared with visual analysis for predicting event-free survival (EFS) and overall survival, using receiver-operating-characteristic (ROC) analysis. Survival curves were estimated with Kaplan-Meier analysis and compared using the log-rank test. RESULTS: With visual analysis, the accuracy of early PET to predict EFS was 65.2%. The 2-y estimate for EFS was 51% (95% confidence interval [CI], 34%-68%) in the PET-positive group compared with 79% (95% CI, 68%-90%) in the PET-negative group (P = 0.009). An optimal cutoff value of 65.7% SUVmax reduction from baseline to midtherapy obtained from ROC analysis yielded an accuracy of 76.1% to predict EFS. The 2-y estimate for EFS was 21% (95% CI, 0%-42%) in patients with SUVmax reduction 65.7% (P < 0.0001). Fourteen patients considered as positive on visual analysis could have been reclassified as good responders. CONCLUSION: SUV-based assessment of therapeutic response during first-line chemotherapy improves the prognostic value of early (18)F-FDG PET compared with visual analysis in DLBCL.     

肺癌MR扩散加权成像ADC与18F-FDG PET/CT代谢成像SUV的相关性研究

目的研究肺癌MR扩散加权成像(DWI)表观扩散系数(ADC)与PET/CT代谢成像标准摄取值(SUV)的相关性。方法搜集本院行胸部MR DWI和PET/CT代谢成像的26例肺癌患者的影像资料,分别测量MRDWI和PET/CT代谢成像对应层面病变实质部分的ADC最小值(ADCmin)、ADC平均值(ADCmean)和SUV最大值(SUVmax)、SUV平均值(SUVmean),计算相对ADC(rADC)(ADCmin/ADCmean)和相对SUV(rSUV)(SUVmax/SUVmean),分析ADCmin与SUVmax,ADCmean与SUVmean以及rADC与rSUV之间的相关性。结果 26例肺癌MR DWI的ADCmin为(0.891±0.167)×10-3mm2/s,ADCmean为(1.244±0.351)×10-3mm2/s,rADC为0.74±0.14;PET/CT代谢成像SUVmax为10.5±4.6,SUVmean为5.6±1.8,rSUV为1.80±0.28。ADCmin与SUVmax没有相关性(P=0.207>0.05),ADCmean与SUVmean没有相关性(P=0.331>0.05),rADC与rSUV呈负相关性(P=0.021<0.05),相关系数为-0.451。结论肺癌的MR DWI rADC与PET/CT代谢成像rSUV存在一定的负相关性,ADC与SUV在肺癌的临床应用中可以互为补充。     

100名健康者肾上腺18F-FDG PET/CT显像分析

目的 探讨正常肾上腺18F-脱氧葡萄糖(FDG) PET显像特征,为在18F-FDG PET或PET/CT显像中判断肾上腺是否有高代谢灶提供依据.方法 选择行PET/CT体格检查的健康者100名.图像分析采用目测计分和测定标准摄取值(SUV)2种方法.目测计分法以肝为对照,肾上腺未显影为0分,放射性摄取低于肝放射性为1分,等于肝放射性为2分,高于肝放射性为3分;SUV由图像横断面测量,依据CT所显示的肾上腺和肝,手动勾画感兴趣区(ROI),获得左右两侧肾上腺、肝的SUV平均值(SUVmax)、SUV最大值(SUVmax),再计算肾上腺与肝SUV的比值.结果 (1)目测分析:左、右侧正常肾上腺放射性摄取分别有94%和91%等于或低于肝.(2)左、右侧正常肾上腺95%可信区间(CI)上限,SUVmax分别为1.39和1.65, SUVmax分别为1.98和2.19.(3)左、右侧正常肾上腺/肝比值的95%CI上限,SUVmax分别为0.65和0.75, SUVmax分别为0.76和0.83.(4)左、右侧肾上腺对18F-FDG摄取有一定差异,右侧肾上腺SUVmax和SUVmax均高于左侧.(5)除右侧SUVmax男性高于女性外,余各组性别差异无统计学意义.(6)正常肾上腺对18F-FDG摄取在＜60岁组和≥60岁组的差异无统计学意义.结论 正常肾上腺18F-FDG生理性摄取程度的主要表现为低于肝.     

Dual time point 18F-FDG PET imaging detects breast cancer with high sensitivity and correlates well with histologic subtypes.

This prospective study was designed to assess the utility of the dual time point imaging technique by (18)F-FDG PET in detecting primary breast cancer and to determine whether there is a relationship between (18)F-FDG uptake and its change over time and the histopathologic subtypes. METHODS: One hundred fifty-two patients with newly diagnosed breast cancer underwent 2 sequential PET scans (dual time point imaging) for preoperative staging. The maximum standardized uptake value (SUVmax) of (18)F-FDG was measured from both time points. The percent change in SUVmax (Delta%SUVmax) between time points 1 (SUVmax1) and 2 (SUVmax2) was calculated. Patients were divided into 2 groups according to histopathology as invasive and noninvasive. Invasive tumors were also divided into 2 groups (>10 mm and 4-10 mm). The tumor-to-contralateral normal breast (background) ratios of SUVmax at both time points for groups were measured and the Delta%SUVmax values were calculated. RESULTS: The mean +/- SD of the SUVmax1, the SUVmax2, and the Delta%SUVmax were 3.9 +/- 3.7, 4.3 +/- 4.0, and 8.3% +/- 11.5% for invasive; 2.0 +/- 0.6, 2.1 +/- 0.6, and 3.4% +/- 13.0% for noninvasive; and were 1.2 +/- 0.3, 1.1 +/- 0.2, and -10.0% +/- 10.8% for the contralateral normal breast groups, respectively. In the comparison of SUVmax1, Delta%SUVmax, and the tumor-to-background ratios among groups, all results were significant (P < 0.001). Visual assessment revealed that the sensitivity of dual time point imaging was 90.1% for invasive cancer >10 mm, 82.7% for invasive breast cancers 4-10 mm, and 76.9% for noninvasive breast cancers. CONCLUSION: Dual time point imaging is a simple and noninvasive method that may improve the sensitivity and accuracy of (18)F-FDG PET in assessing patients with primary breast cancer. The changes that are noted in SUVs in dual time point imaging vary depending on the histopathologic type of primary breast cancer.     

18F-FET PET compared with 18F-FDG PET and CT in patients with head and neck cancer.

Recent studies suggest a somewhat selective uptake of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) in cerebral gliomas and in squamous cell carcinoma (SCC) and a good distinction between tumor and inflammation. The aim of this study was to investigate the diagnostic potential of 18F-FET PET in patients with SCC of the head and neck region by comparing that tracer with 18F-FDG PET and CT. METHODS: Twenty-one patients with suspected head and neck tumors underwent 18F-FET PET, 18F-FDG PET, and CT within 1 wk before operation. After coregistration, the images were evaluated by 3 independent observers and an ROC analysis was performed, with the histopathologic result used as a reference. Furthermore, the maximum standardized uptake values (SUVs) in the lesions were determined. RESULTS: In 18 of 21 patients, histologic examination revealed SCC, and in 2 of these patients, a second SCC tumor was found at a different anatomic site. In 3 of 21 patients, inflammatory tissue and no tumor were identified. Eighteen of 20 SCC tumors were positive for both 18F-FDG uptake and 18F-FET uptake, one 0.3-cm SCC tumor was detected neither with 18F-FDG PET nor with 18F-FET PET, and one 0.7-cm SCC tumor in a 4.3-cm ulcer was overestimated as a 4-cm tumor on 18F-FDG PET and missed on 18F-FET PET. Inflammatory tissue was positive for 18F-FDG uptake (SUV, 3.7-4.7) but negative for 18F-FET uptake (SUV, 1.3-1.6). The SUVs of 18F-FDG in SCC were significantly higher (13.0 +/- 9.3) than those of 18F-FET (4.4 +/- 2.2). The ROC analysis showed significantly superior detection of SCC with (18)F-FET PET or 18F-FDG PET than with CT. No significant difference (P = 0.71) was found between 18F-FDG PET and 18F-FET PET. The sensitivity of 18F-FDG PET was 93%, specificity was 79%, and accuracy was 83%. 18F-FET PET yielded a lower sensitivity of 75% but a substantially higher specificity of 95% (accuracy, 90%). CONCLUSION: 18F-FET may not replace 18F-FDG in the PET diagnostics of head and neck cancer but may be a helpful additional tool in selected patients, because 18F-FET PET might better differentiate tumor tissue from inflammatory tissue. The sensitivity of 18F-FET PET in SCC, however, was inferior to that of 18F-FDG PET because of lower SUVs.     

Whole-body tumor imaging using PET and 2-18F-fluoro-L-tyrosine: preliminary evaluation and comparison with 18F-FDG.

18F-FDG PET imaging is now established as a valuable tool for evaluating cancer patients. However, a limitation of (18)F-FDG is its absence of specificity for tumor. Both protein synthesis and amino acid transport are enhanced in most tumor cells, but their metabolism is less affected in inflammation. We therefore decided to evaluate the ability of PET with 2-(18)F-fluoro-L-tyrosine ((18)F-TYR) to visualize cancer lesions in patients compared with (18)F-FDG PET. METHODS: (18)F-FDG PET and (18)F-TYR PET were performed on 23 patients with histologically proven malignancies (11 non-small cell lung cancers (NSCLCs), 10 lymphomas, and 2 head and neck carcinomas). Fully corrected, whole-body PET studies were obtained on separate days. (18)F-FDG studies were performed after routine clinical fashion. (18)F-TYR studies were started 36 +/- 6 min after tracer injection and a second scan centered over a reference lesion was acquired after completion of the whole-body survey-on average, 87 min after injection. Standardized uptake values (SUVs) were calculated for all abnormal foci and for various normal structures. Results were compared with pathologic or correlative studies. RESULTS: (18)F-FDG PET correctly identified 54 malignant lesions, among which 36 were also visualized with (18)F-TYR (67%). (18)F-TYR did not detect any additional lesion. Tumor SUVs (SUV(bw), 5.2 vs. 2.5), tumor-to-muscle (7.4 vs. 2.7), and tumor-to-mediastinum activity ratios (3 vs. 1.4) were higher with (18)F-FDG than with (18)F-TYR. Two of 11 NSCLCs and 4 of 10 lymphomas were understaged with (18)F-TYR compared with (18)F-FDG. Although the NSCLC lesions missed by (18)F-TYR PET were small, several large lymphoma lesions did not accumulate the tracer. In 4 patients, (18)F-TYR-positive lesions coexisted with (18)F-TYR-negative lesions. There was a high physiologic (18)F-TYR uptake by the pancreas (average SUV(bw), 10.3) and the liver (average SUV(bw), 6.3). Muscle and bone marrow uptakes were also higher with (18)F-TYR than with (18)F-FDG: average SUV(bw), 1 versus 0.7 and 2.6 versus 1.8, respectively. There was no change over time in the (18)F-TYR uptake by the tumors or the normal structures. CONCLUSION: (18)F-TYR PET is not superior to (18)F-FDG PET for staging patients with NSCLC and lymphomas.     

Reproducibility of metabolic measurements in malignant tumors using FDG PET.

PET using 18F-fluorodeoxyglucose (FDG) is increasingly applied to monitor the response of malignant tumors to radiotherapy and chemotherapy. The aim of this study was to assess the reproducibility of serial FDG PET measurements to define objective criteria for the evaluation of treatment-induced changes. METHODS: Sixteen patients participating in phase I studies of novel antineoplastic compounds were examined twice by FDG PET within 10 d while they were receiving no therapy. Standardized uptake values (SUVs), FDG net influx constants (Ki), glucose normalized SUVs (SUV(gluc)) and influx constants (K(i,gluc)) were determined for 50 separate lesions. The precision of repeated measurements was determined on a lesion-by-lesion and a patient-by-patient basis. RESULTS: None of the parameters showed a significant increase or decrease at the two examinations. The differences of repeated measurements were approximately normally distributed for all parameters with an SD of the mean percentage difference of about 10%. The 95% normal ranges for spontaneous fluctuations of SUV, SUV(gluc), Ki and K(i,gluc) were determined to be +/-0.91, +/-1.14, +/-0.52 mL/100 g/min and +/-0.64 mL/100 g/min, respectively. Analysis on a lesion-by-lesion basis yielded similar results. CONCLUSION: FDG PET provides several highly reproducible quantitative parameters of tumor glucose metabolism. Changes of a parameter that are outside the 95% normal range determined in this study may be used to define a metabolic response to therapy.     

Evaluation of delayed18F-FDG PET in differential diagnosis for malignant soft-tissue tumors

OBJECTIVE: Positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) has been used for the evaluation of soft-tissue tumors. However, the range of accumulation of 18F-FDG for malignant soft-tissue lesions overlaps with that of benign lesions. The aim of this study is to investigate the usefulness of delayed 18F-FDG PET imaging in the differentiation between malignant and benign soft-tissue tumors. METHODS: Fifty-six patients with soft-tissue tumors underwent whole body 18F-FDG PET scan at 1 hour (early scan) and additional scan at 2 hours after injection (delayed scan). The standardized uptake value (SUV(max)) of the tumor was determined, and the retention index (RI) was defined as the ratio of the increase in SUV(max) between early and delayed scans to the SUV(max) in the early scan. Surgical resection with histopathologic analysis confirmed the diagnosis. RESULTS: Histological examination proved 19 of 56 patients to have malignant soft-tissue tumors and the rest benign ones. In the scans of all 56 patients, there was a statistically significant difference in the SUV(max) between malignant and benign lesions in the early scan (5.50 +/- 5.32 and 3.10 +/- 2.64, respectively, p < 0.05) and in the delayed scan (5.95 +/- 6.40 and 3.23 +/- 3.20, respectively, p < 0.05). The mean RI was not significantly different between malignant and benign soft-tissue tumors (0.94 +/- 23.04 and -2.03 +/- 25.33, respectively). CONCLUSIONS: In the current patient population, no significant difference in the RI was found between malignant and benign soft-tissue lesions. Although the mean SUV(max) in the delayed scan for malignant soft-tissue tumors was significantly higher than that for benign ones, there was a marked overlap. The delayed 18F-FDG PET scan may have limited capability to differentiate malignant soft-tissue tumors from benign ones.     

Comparative evaluation of 18F-FDG PET and 67Ga scintigraphy in patients with sarcoidosis.

67Ga scintigraphy has been used for years in sarcoidosis for diagnosis and the extent of the disease. However, little information is available on the comparison of 18F-FDG PET and 67Ga scintigraphy in the assessment of sarcoidosis. The purpose of this study was to compare the uptake of 18F-FDG and 67Ga in the evaluation of pulmonary and extrapulmonary involvement in patients with sarcoidosis. METHODS: Eighteen patients with sarcoidosis were examined. 18F-FDG PET was performed at 1 h after injection of 185-200 MBq 18F-FDG. 67Ga whole-body planar and thoracic SPECT images were acquired 72 h after injection of 111 MBq 67Ga. We evaluated 18F-FDG and 67Ga uptake visually and semiquantitatively using standardized uptake values (SUVs) and the ratio of lesion to normal lumbar spine (L/N ratio), respectively. The presence of pulmonary and extrapulmonary lesions was evaluated histopathologically or by the radiologic findings. RESULTS: Five patients had only pulmonary lesions, 12 patients had both pulmonary and extrapulmonary lesions, and 1 patient had only an extrapulmonary lesion. Both 67Ga planar and SPECT images detected 17 of 21 (81%) clinically observed pulmonary sites. The mean +/- SD of the L/N ratio was 1.97 +/- 1.09. 67Ga planar images detected 15 of 31 (48%) clinically observed extrapulmonary sites. The mean +/- SD of the L/N ratio was 1.17 +/- 0.33. 18F-FDG PET detected all 21 (100%) clinically observed pulmonary sites. The mean +/- SD of the SUV was 7.40 +/- 2.48. 18F-FDG PET detected 28 of 31 (90%) clinically observed extrapulmonary sites. The mean +/- SD of the SUV was 5.90 +/- 2.75. CONCLUSION: The results of this clinical study suggest that 18F-FDG PET can detect pulmonary lesions to a similar degree as 67Ga scintigraphy. However, 18F-FDG PET appears to be more accurate and contributes to a better evaluation of extrapulmonary involvement in sarcoidosis patients.     

18F-FDG PET for mediastinal staging of lung cancer: which SUV threshold makes sense?

(18)F-FDG PET is the most accurate noninvasive modality for staging mediastinal lymph nodes in lung cancer. Besides using visual image interpretation, some institutions use standardized uptake value (SUV) measurements in lymph nodes. Mostly, an SUV of 2.5 is used as the cutoff, but this choice was never deduced from respective studies. Receiver operating characteristic (ROC) analyses demonstrated that SUV thresholds of more than 4 resulted in the highest accuracy. But these high cutoffs imply high false-negative rates (FNRs). The aim of our evaluation was to determine an optimal SUV threshold and to compare its diagnostic performance with the results of visual interpretation. METHODS: This retrospective study included 95 patients with suspected lung cancer who underwent mediastinoscopy/mediastinal lymphadenectomy after (18)F-FDG PET (90-150 min after 250 MBq of (18)F-FDG). Maximum SUV was measured in 371 lymph node regions biopsied afterward and visually interpreted using a 6-level score (- - - through + + +). Diagnostic performance was assessed by ROC analysis. FNR and false-positive rate (FPR), the sum of both error rates (FNR + FPR), and diagnostic accuracy were plotted against a hypothetical SUV threshold to determine the optimum SUV threshold. RESULTS: SUVs in metastatic lymph nodes were higher (mean +/- SD, 7.1 +/- 4.5; range, 1.4-26.9; n = 70) than in tumor-free lymph node stations (2.4 +/- 1.7; range, 0.6-14.9; n = 301; P < 0.01). Inflammatory lymph nodes exhibited slightly increased SUVs (2.7 +/- 2.0; range, 0.8-14.9; n = 146). The plot of error rates featured a minimum of the sum FNR + FPR for an SUV of 2.5. With increasing SUV threshold, the FPR decreased most prominently up to that value whereas a continuous rise of FNR was noticed. Highest diagnostic accuracy was achieved with an SUV of 4.5. The areas under the ROC curves demonstrated that visual interpretation tends to be more accurate than SUV quantification (visual, 0.930 +/- 0.022; SUV, 0.899 +/- 0.025; P = 0.241). Using an SUV of 2.5 as the threshold, the resulting sensitivity, specificity, and negative predictive value were 89%, 84%, and 96%, respectively. CONCLUSION: For mediastinal staging, the choice of an SUV of 2.5 as the threshold is justified because FNR + FPR is minimized. The resulting high negative predictive value of 96% allows the omission of mediastinoscopy in patients with negative mediastinal findings on (18)F-FDG PET images. For the experienced observer, visual analysis should be relied on primarily, with calculation of the SUV used, at most, as a secondary aid. For the less experienced observer, the SUV may be of greater value.     

18F-FDG PET is an early predictor of pathologic tumor response to preoperative radiochemotherapy in locally advanced rectal cancer.

18F-FDG PET is a useful tool for assessing the effects of chemo- or radiotherapy. The aim of this study was to correlate the change in tumor 18F-FDG standardized uptake value (SUV) during and after preoperative radiochemotherapy, with the pathologic response achieved in locally advanced rectal cancer (LARC) patients. METHODS: Thirty-three patients with LARC underwent total mesorectal excision after preoperative treatment, including 3 cycles of oxaliplatin, raltitrexed, 5-fluorouracil, and folinic acid during pelvic radiotherapy (45 Gy). Staging procedures included endoscopic ultrasound, MRI, and CT. 18F-FDG PET scans were performed at baseline and 12 d after starting radiochemotherapy (intermediate) in all patients. Seventeen patients also had a presurgical scan. For each scan, mean and maximum SUVs were measured. The percentages of SUV decrease from baseline to intermediate (early change) and to presurgical scan (overall change) were assessed and correlated with pathologic response classified as tumor regression grade (TRG). RESULTS: Eighteen tumors (55%) showed complete (TRG1) or subtotal regression (TRG2) and were classified as responders, whereas 15 cases (45%; TRG3 or TRG4) were considered nonresponders. The early median decrease of tumor SUV significantly differed between responders (-62%; range, -44% to -100%) and nonresponders (-22%; range, -2% to -48%). A significant correlation was also found between TRGs and early SUV changes (P < 0.0001). Responders were identified correctly by an early decrease of the mean SUV of > or =52%. CONCLUSION: This study shows that early 18F-FDG PET can predict pathologic response to preoperative treatment. These findings support the usefulness of (18)F-FDG PET during the management with radiochemotherapy of LARC patients.     

Detection of Klatskin's tumor in extrahepatic bile duct strictures using delayed 18F-FDG PET/CT: preliminary results for 22 patient studies.

Detection of cholangiocarcinoma in extrahepatic bile duct strictures is a continuing challenge in clinical practice because brush cytology taken at endoscopic retrograde cholangiography has an average sensitivity of 50%. The aim of this study was to evaluate the effectiveness of dual-modality PET/CT using (18)F-FDG for noninvasive differentiation of extrahepatic bile duct strictures. METHODS: Twenty-two PET/CT studies were performed on 20 patients (10 women, 10 men; mean age +/- SD, 63 +/- 14 y) with extrahepatic bile duct strictures on endoscopic retrograde cholangiography. PET imaging was started 101 +/- 22 min after injection of 369 +/- 48 MBq of 18F-FDG. Blood glucose was 100 +/- 20 mg/dL. PET images were reconstructed iteratively with attenuation correction based on a rescaling of the CT image. CT was performed within 1 min before the PET study, with the patient in the same position. CT was used to place a volume of interest 5 cm in diameter at the liver hilus for quantitative evaluation of PET images by means of standardized uptake values (SUVs). RESULTS: Final diagnosis was histologically proven cholangiocarcinoma in 14 cases and benign causes of strictures in 8 cases without evidence of malignancy during a follow-up of 18 +/- 3 mo. All patients with cholangiocarcinoma presented with focal increased uptake in the liver hilus with an SUV of 6.8 +/- 3.3 (range, 3.9-15.8), compared with 2.9 +/- 0.3 (range, 2.5-3.3) in patients with benign causes of strictures (P = 0.003). There was a clear cutoff SUV of 3.6 for detection of malignancy in the liver hilus. CONCLUSION: 18F-FDG PET/CT provided high accuracy for noninvasive detection of perihilar cholangiocarcinoma in extrahepatic bile duct strictures.     

Decreased 18F-FDG uptake 1 day after initiation of chemotherapy for malignant lymphomas.

Several recent reports have described the judgment of chemotherapeutic effects on malignant lymphomas by use of (18)F-FDG PET as early as a few courses after the initiation of chemotherapy. However, the optimal timing of (18)F-FDG PET has yet to be clarified. Earlier (18)F-FDG PET, such as day 1 after chemotherapy, may be affected by inflammation or chemotoxicity in addition to chemotherapeutic effects, but the ways in which uptake is changed are as yet unclear. We therefore examined changes in (18)F-FDG PET results on day 1 after the initiation of chemotherapy for malignant lymphoma. METHODS: Twelve patients with non-Hodgkin's lymphoma were enrolled in this study. (18)F-FDG PET was performed before therapy to determine baseline results and then was repeated at day 1 and day 20 after the initiation of chemotherapy (just before the initiation of the second course of chemotherapy) and at the end of chemotherapy. We selected 1-9 regions of interest (ROIs) from each patient and calculated the corrected standardized uptake value (SUV(cor)) by subtracting the SUV of surrounding normal tissue for a semiquantitative analysis. From the ROIs in each patient, the representative SUV(cor) with the highest SUV(cor) at baseline was selected, and the mean representative SUV(cor)s for all 12 patients at baseline, day 1, day 20, and the end of chemotherapy were evaluated. Changes in the representative SUV(cor) were compared by use of paired t tests (2-tailed P values of <0.05 were considered statistically significant). RESULTS: All representative SUV(cor)s for each patient were lower on day 1 than at baseline, and the mean +/- SD representative SUV(cor) for all patients was significantly decreased from 10.7 +/- 7.9 at baseline to 5.8 +/- 5.8 at day 1 (P = 0.0002; paired t test). On day 20, the mean +/- SD SUV(cor) was 0.7 +/- 1.0, showing a further decrease from the value at day 1 (P = 0.01). Although the mean +/- SD SUV(cor) tended to decrease again to 0.4 +/- 0.7 by the end of chemotherapy compared with the value at day 20, no significant difference was identified (P = 0.37). CONCLUSION: (18)F-FDG uptake decreased as early as day 1 after the initiation of chemotherapy, indicating that (18)F-FDG PET for initial diagnosis or staging must be performed before the onset of chemotherapy, as scan results might already be severely compromised after the first day.     

Characterization of the normal adrenal gland with 18F-FDG PET/CT.

Prior studies have documented increased (18)F-FDG adrenal activity in both benign and malignant pathologic conditions. When whole-body PET imaging is performed without CT anatomic coregistration, however, the normal adrenal gland is difficult to recognize. The purpose of this study was to investigate the normal adrenal appearance and standardized uptake value (SUV) using (18)F-FDG PET/CT imaging. METHODS: Twenty patients with lymphoma with normal-appearing adrenal glands on prior CT examination (less than a 5% pretest likelihood of adrenal involvement) were studied. PET/CT imaging was performed 2 h after intravenous administration of (18)F-FDG. Unenhanced CT scans were acquired for attenuation correction and anatomic coregistration. PET images were reconstructed using an ordered-subsets expectation maximization algorithm and were corrected for body weight, dose, and radioactive decay. Ability to confirm visualization of the adrenal glands was determined for (18)F-FDG PET alone and for (18)F-FDG PET/CT by a consensus of 2 readers, and uptake of (18)F-FDG in the adrenal gland was compared with liver activity and scored visually (0 = no visualization, 1 = activity less than in liver, 2 = activity equal to liver activity, and 3 = activity greater than in liver). RESULTS: The 2 readers agreed on visualization of the adrenal glands with PET alone for 2 of 40 (5%) glands. With PET/CT, the readers agreed on visualization of 27 of 40 (68%) adrenal glands. Visual scores for normal adrenal activity ranged from 0 to 3, and maximum SUVs ranged from 0.95 to 2.46. Visual scoring of adrenal activity correlated well with both mean and maximal SUV (mean SUV vs. visual score: slope = 0.96, r = 0.88; maximum SUV vs. visual score: slope = 0.99, r = 0.87). CONCLUSION: PET/CT permits more reliable visualization of normal adrenal glands than does PET alone. Visual assessment of adrenal uptake correlates well with SUV measurement, and readers of PET/CT need to be aware of the wide range of normal adrenal uptake.     

Evaluation of various corrections to the standardized uptake value for diagnosis of pulmonary malignancy

OBJECTIVE: Standard uptake values (SUVs) are widely used for quantifying the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours. The objective of this study was to evaluate the accuracy of SUVs for malignancy in lung nodules/masses and to analyse the effects of tumour size, blood glucose levels and different body weight corrections on SUV. METHODS: One hundred and twenty-seven patients with suspicious lung lesions imaged with 18F-FDG positron emission tomography (PET) were studied retrospectively. Pathology results were used to establish lesion diagnosis in all cases. SUVs based on maximum pixel values were obtained by placing regions of interest around the focus of abnormal 18F-FDG uptake in the lungs. The SUVs were calculated using the following normalizations: body weight (BW), lean body weight (LBW), scaled body surface area (BSA), blood glucose level (Glu) and tumour size (Tsize). Receivers operating characteristic (ROC) curves were generated to compare the accuracy of different methods of SUV calculation. RESULTS: The areas under the ROC curves for SUV(BW), SUV(BW+Glu), SUV(LBW), SUV(LBW+Glu), SUV(BSA), SUV(BSA+Glu) and SUV(BW+Tsize) were 0.915, 0.912, 0.911, 0.912, 0.916, 0.909 and 0.864, respectively. CONCLUSION: The accuracy of SUV analysis for malignancy in lung nodules/masses is not improved by correction for blood glucose or tumour size or by normalizing for body surface area or lean body weight instead of body weight.