Determination of the prognostic value of [(18)F]fluorodeoxyglucose uptake by using positron emission tomography in patients with non-small cell lung cancer

The aim of this study was to determine whether quantitative information obtained from [(18)F]fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) has a prognostic significance for patients with non-small cell lung cancer (NSCLC). We investigated (18)F-FDG PET imaging of 73 patients with NSCLC. The maximum standardized uptake value (SUV(max)) was significantly different between the histopathological types of tumour (squamous cell carcinoma (n=37, 12.4+/-5.1), adenocarcinoma (n=30, 8.2+/-5.8), bronchioloalveolar carcinoma (n=4, 2.6+/-1.7), <0.01). In the univariate analysis of all patients, staging (P=0.0001), tumour cell type (P=0.013), and a SUV(max) greater than 7 (P=0.0011) was correlated with survival. However, a multivariate analysis identified staging and SUV(max) greater than 7 were affected survival adversely. The mortality rate of patients with group I disease (stage I to stage IIIA) was 5.8 times lower than that of patients with group II disease (stage IIIB to stage IV). Patients with a high SUV(max) (> or =7) had a 6.3 times higher mortality than those with a low SUV(max)(<7). By multivariate analysis of patients with squamous cell carcinoma, only grouping affected survival (P=0.008, relative risk=4.3). In the case of adenocarcinoma, the SUV(max) (>10) correlated exclusively with poorer survival (P=0.031, relative risk=11.152). (18)F-FDG uptake correlated with survival in NSCLC. Especially in adenocarcinomas, the SUV(max) was complementary to other known prognostic factors.     

Bone marrow hypermetabolism on 18F-FDG PET as a survival prognostic factor in non-small cell lung cancer.

PET is now widely used in the diagnosis and staging of lung cancer with (18)F-FDG. The purpose of the study was to evaluate the prognostic value of diffuse bone marrow hypermetabolism along with other PET prognostic factors with respect to survival and compare them with other established prognostic factors in a large cohort of patients. METHODS: Of 255 patients referred for evaluation of a suspicious lung lesion by PET over an 8-mo period (May 1999 to January 2000), the outcome of 120 patients with a final diagnosis of primary non-small cell lung cancer was analyzed retrospectively after excluding subjects with benign, metastatic, or recurrent lesions, using the available follow-up information and a provincial mortality database. Kaplan-Meier survival curves were compared using the mean and the maximal tumor standardized uptake value (SUV), bone marrow SUV, PET stage, various laboratory parameters, sex, age, conventional imaging stage, and pathologic stage. A stepwise Cox proportional hazard model was built using the significant variables on univariate analysis. RESULTS: The primary tumor SUV (>10), bone marrow uptake of (18)F-FDG, (18)F-FDG PET stage, pathologic stage, hypercalcemia, lactate dehydrogenase, hemoglobin, albumin, thrombocytopenia, thrombocytosis, and leukocytosis were predictors of mortality on univariate analysis. On multivariate analysis, bone marrow hypermetabolism, (18)F-FDG PET nodal stage, and some hematologic parameters (hemoglobin, platelets, white blood cell counts) remained significant independent predictors of mortality. CONCLUSION: Bone marrow hypermetabolism and the PET nodal stage were strong independent predictors of mortality in patients with lung cancer. The primary tumor SUV, though predictive on univariate analysis, was not an independent predictor of mortality in our model.     

18F-FDG uptake as a biologic prognostic factor for recurrence in patients with surgically resected non-small cell lung cancer.

Among patients with resected non-small cell lung cancer (NSCLC), approximately 50% present with a recurrent tumor. The clinical or pathologic TNM staging does not always provide a satisfactory explanation for differences in relapse and survival. Thus, it is of major importance to be able to predict these relapses and to prevent them with an active chemotherapy or radiotherapy program (or both). 18F-FDG uptake on PET could be of prognostic significance in patients with resected NSCLC. The goal of this study was to determine whether the level of metabolic activity observed with 18F-FDG uptake correlates with the probability of postoperative recurrence in patients with NSCLC. METHODS: Fifty-seven patients with NSCLC were examined with 18F-FDG PET. For semiquantitative analysis, standardized uptake values (SUVs) were calculated. Patients were classified into high-SUV (> 5.0) and low-SUV (< or = 5.0) groups. All patients underwent thoracotomy within 4 wk after the 18F-FDG PET study. Tumor 18F-FDG uptake (SUV), pathologic stage, and lesion size were analyzed for their possible association with disease-free survival. RESULTS: Forty-six patients had pathologic stage I NSCLC and 11 had pathologic stage II or stage III NSCLC. In a univariate analysis, patients with an SUV of < or = 5 had a much better disease-free survival than did patients with an SUV of > 5 (P < 0.0001). In patients with pathologic stage I and stage IA NSCLC, the SUV was also correlated with disease-free survival (P < 0.0001 and P = 0.0012, respectively). Patients with pathologic stage I disease had an expected 5-y disease-free survival rate of 88% if the SUV was < or = 5 and a survival rate of < or = 17% if the SUV was > 5. A multivariate Cox analysis identified the SUV as the most significant independent factor for disease-free survival. CONCLUSION: We conclude that the 18F-FDG uptake in primary NSCLC determined by PET has a significant independent postoperative prognostic value for recurrence, especially in patients with pathologic stage I NSCLC. 18F-FDG uptake was superior to pathologic stage in predicting relapse of patients with NSCLC.     

11C-胆碱与18F-FDG双时相PET显像在孤立性肺结节鉴别诊断中的应用

目的 比较^11C-胆碱、18F-脱氧葡萄糖（FDG）和^18F-FDG双时相PET显像对鉴别肺部孤立性结节良恶性的价值。方法16例临床疑为肺肿瘤的患者进行^18F-FDGPET显像（注药后1h显像，2h后行延迟显像）、^11C-胆碱PET显像（3d内，于注药后10min进行）。图像判断以标准摄取值（SUV）作为半定量指标，异常放射性浓聚灶以SUV〉2．5为葡萄糖代谢增高，^18F-FDG延迟显像SUV上升≥10％为恶性病变（阳性），如下降或升高〈10％为良性病变（阴性）；^11C-胆碱异常摄取灶以SUV〉2．0为阳性。所有病例进行随访，以显像诊断是否符合病理检查结果作为判断标准。结果病理检查结果证实12例肺癌，3例结核，1例结节病。^11C-胆碱PET显像确诊了12例肿瘤中的ll例，而^18F-FDG PET显像确诊10例（10／12例），双时相^18F-FDG PET显像确诊11例。4例良性病变者，^11C-胆碱PET显像能较好鉴别；而^18F-FDG PET显像2例假阳性，结合延迟显像仅1例假阳性。结论 ^11C-胆碱和^18F-FDG PET显像均能较好地鉴别肺部良恶性肿瘤。但^11C-胆碱和双时相^18F-FDGPET显像优于常规^18F-FDGPET显像，三者联合能提高对肺部病变的诊断效率。     

血管内皮生长因子D表达对肺腺癌FDG摄取程度及淋巴结转移的影响

目的探讨肺腺癌中血管内皮生长因子D（VEGF—D）表达水平对病灶^18F-脱氧葡萄糖（FDG）摄取程度的影响,以及评价VEGF—D可否作为预测肺腺癌淋巴结转移的指标之一。方法使用抗VEGF—D抗体对49例肺腺癌病理石蜡包埋切片行免疫组织化学染色。所有患者常规行PET检查,感兴趣区的定量分析采用标准摄取值（SUV）。使用独立样本t检验,χ^2检验及F检验行统计学分析,使用Kaplan·Meier方法计算无瘤生存曲线（log rank分析）。结果（1）在所有病例中及在非细支气管肺泡癌（BAC）病例中,VEGF-D阴性组的FDG摄取程度明显高于阳性组（所有病例SUV分别为4．84±2．14和2．35±1．45,t=4．853,非BAC病例SUV分别为5．26±1．86和2．94±1．40,t=4．266,P均〈0．001）。（2）在所有患者及在非BAC病例中,VEGF—D阳性组中发生淋巴结转移（均为0例χ^2=18．988和15．000,P均〈0．001）及复发（均为5例,χ^2=16．432和12．255,P〈0．001和=0．001）的病例数均明显低于VEGF—D阴性组（所有患者和非BAC患者转移及复发例数均为9例和均为13例）。VEGF—D阳性组中,低度恶性的病例（2组分别为23和12例）均多于高度恶性的病例（均为8例,χ^2=10．018和6．223,P值分别为0．002,0．013）。（3）VEGF—D阳性的患者其无瘤生存率明显高于阴性者[83．33％（25／30）与23．53％（4／17）,χ^2=14．05,P〈0．001]。结论高FDG摄取的肺腺癌患者VFGF—D呈明显低表达,且VEGF—D可能作为肺腺癌患者淋巴结转移、组织学分型及复发的预测指标。     

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.     

Relationship between retention index in dual-phase (18)F-FDG PET, and hexokinase-II and glucose transporter-1 expression in pancreatic cancer.

Recently, some studies have shown that delayed scanning with (18)F-FDG PET may help to differentiate malignant from benign pancreatic lesions. However, no study has evaluated the relationship between temporal changes in (18)F-FDG uptake and expression of hexokinase or glucose transporter. METHODS: Twenty-one consecutive patients with pancreatic cancer were studied preoperatively by dual-phase (18)F-FDG PET, performed 1 and 2 h after injection of (18)F-FDG. The standardized uptake value (SUV) of the pancreatic cancer was determined, and the retention index (RI) (%) was calculated by subtracting the SUV at 1 h (SUV1) from the SUV at 2 h (SUV2) and dividing by SUV1. The percentages of cells strongly expressing hexokinase type-II (HK-II) and glucose transporter-1 (GLUT-1) were scored on a 5-point scale (1 = 0%-20%, 2 = 20%-40%, 3 = 40%-60%, 4 = 60%-80%, 5 = 80%-100%) by visual analysis of immunohistochemical staining of paraffin sections from the tumor specimens using anti-HK-II and anti-GLUT-1 antibody (HK-index and G-index, respectively). RESULTS: SUV2 (mean +/- SD, 5.7 +/- 2.6) was higher than SUV1 (5.1 +/- 2.1), with an RI of 8.5 +/- 11.0. Four cases of cancer, in which SUV2 showed a decline from SUV1, showed a low HK-index (1.8 +/- 1.1), whereas 4 cases with an RI of > or =20 and 13 cases with an intermediate RI (0-20) showed significantly higher HK-indices (4.3 +/- 0.7 and 3.1 +/- 1.5, respectively; P < 0.05). RI showed a positive correlation with HK-index, with an R(2) of 0.27 (P < 0.05), but no significant correlation with the G-index. SUV1 showed no relationship with the HK-index but showed a weak positive correlation with the G-index, with an R(2) of 0.05 (P = 0.055). CONCLUSION: These preliminary findings suggest that the RI obtained from dual-phase (18)F-FDG PET can predict HK-II expression and that the SUV (at 1 h) has a positive correlation with GLUT-1 expression but not with HK-II expression.     

Lack of correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in non-small cell lung cancer assessed by 18F-Fluoromisonidazole and 18F-FDG PET.

PET offers a noninvasive means to assess neoplasms, in view of its sensitivity and accuracy in staging tumors and potentially in monitoring treatment response. The aim of this study was to evaluate newly diagnosed non-small cell lung cancer (NSCLC) for the presence of hypoxia, as indicated by the uptake of (18)F-Fluoromisonidazole ((18)F-FMISO), and to examine the relationship of hypoxia to the uptake of (18)F-FDG, microvessel density, and other molecular markers of hypoxia. METHODS: Twenty-one patients with suspected or biopsy-proven NSCLC were enrolled prospectively in this study. All patients had PET studies with (18)F-FMISO and (18)F-FDG. Seventeen patients subsequently underwent surgery, with analysis performed for tumor markers of angiogenesis and hypoxia. RESULTS: In the 17 patients with resectable NSCLC (13 men, 4 women; age range, 51-77 y), the mean (18)F-FMISO uptake in tumor was significantly lower than that of (18)F-FDG uptake (P < 0.0001) and showed no correlation with (18)F-FDG uptake (r = 0.26). The mean (95% confidence interval [CI]) (18)F-FMISO SUV(max) (maximum standardized uptake value) was 1.20 [0.95-1.45] compared with the mean [95% CI] (18)F-FDG SUV(max) of 5.99 [4.62-7.35]. The correlation between (18)F-FMISO uptake, (18)F-FDG uptake, and tumor markers of hypoxia and angiogenesis was poor. A weakly positive correlation between (18)F-FMISO and (18)F-FDG uptake and Ki67 was found. CONCLUSION: The hypoxic cell fraction of primary NSCLC is consistently low, and there is no significant correlation in NSCLC between hypoxia and glucose metabolism in NSCLC assessed by (18)F-FDG. These findings have direct implications in understanding the role of angiogenesis and hypoxia in NSCLC biology.     

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.     

晚期乳腺癌18F-FDG PET-CT显像标准摄取值与预后的相关性

目的 探讨晚期乳腺癌18 F-FDG PET-CT显像标准摄取值与预后的相关性.方法 选择68例晚期乳腺癌患者,记录诊断时PET-CT的SUV值,均给予全身静脉化疗,以SUV值8为分界点,将本组患者分为两组,随访5年,观察SUV值与5年生存率的关系.结果 本组观察的68例患者,SUV值越小,生存期相对越长,反之,生存期则相对较短.结论 18F-FDG PET-CT显像标准摄取值(SUV值)对乳腺癌的预后有一定价值,值得临床进一步研究.     

Lactate, choline, and creatine levels measured by vitro 1H-MRS as prognostic parameters in patients with non-small-cell lung cancer

PURPOSE: To determine the biochemical characteristics of lung cancer tissue using in vitro (1)H-MRS, and investigate the correlation between survival probabilities and lactate (Lac), creatine (Cr), and choline (Cho) concentrations measured by in vitro (1)H-MRS. MATERIALS AND METHODS: A total of 21 patients with lung cancer were included in this retrospective study. (1)H-MRS spectra measurements were performed at 6.35T using a JNM-EX270, high-resolution FT-NMR spectrometer. RESULTS: When normal lung tissue was compared with lung cancer tissue, significant differences were noted most consistently in the levels of Lac and Cho, with lung cancer tissue showing higher values than normal lung tissue. Lac concentrations of lung cancer tissue were significantly higher in patients with recurrence compared to patients without recurrence (0.285 +/- 0.096 mumol/g). The mean overall survival of patients in the low-Lac group was 50.28 +/- 6.47 months, which is significantly higher compared to the high-Lac group, which had a mean survival time of only 30.49 +/- 5.41 months. CONCLUSION: Kaplan-Meier analysis of the data showed that the overall and disease-free survival probabilities were significantly higher in patients with low tumor Lac values than in those with high tumor Lac concentrations.     

FDG PET in the evaluation of the aggressiveness of pulmonary adenocarcinoma: correlation with histopathological features

2-[Fluorine-18]fluoro-2-deoxy-d-glucose (FDG) uptake within the primary lesion correlates with survival on positron emission tomography (PET) studies of patients with non-small cell lung cancer. The more metabolically active the tumour, the worse the outcome. The aim of this study was to determine whether a correlation exists between aggressiveness as determined by pathology and the findings of FDG PET in pulmonary adenocarcinoma. Thirty-five patients with 38 adenocarcinomas of the lung were studied. All patients underwent thoracotomy within 4 weeks of the FDG PET study. For semiquantitative analysis, standardized uptake values (SUVs) were calculated. Patients were classified into high SUV (> or = 4.0) and low SUV (<4.0) groups. The degree of FDG uptake (SUVs) in primary lung lesions was correlated with the histopathological features of aggressiveness (pleural involvement, vascular invasion or lymphatic permeation). The mean SUV of aggressive adenocarcinomas (4.36+/-1.94, n = 22) was higher than that of non-aggressive ones (1.53+/-0.88, n = 16) (P < 0.0001). Tumours with a high FDG uptake have a significantly higher likelihood of aggressiveness than those with a low FDG uptake (P = 0.0004). Analysis by the Kaplan-Meier methods revealed that the groups had different prognoses (log-rank test, P = 0.0099). The high SUV group had a significantly worse prognosis. In conclusion, a correlation was seen between aggressiveness as determined by pathology and glucose metabolism as measured by FDG PET in adenocarcinoma of the lung. FDG PET may be used as a non-invasive diagnostic technique in measuring aggressiveness and prognosis in patients with pulmonary adenocarcinoma.     

Imaging of adrenal incidentalomas with PET using (11)C-metomidate and (18)F-FDG.

Our aim was to evaluate the use of PET with (11)C-metomidate and (18)F-FDG for the diagnosis of adrenal incidentalomas. METHODS: Twenty-one patients underwent hormonal screening before dynamic imaging of the upper abdomen with (11)C-metomidate, and for 19 of these 21 patients, static (18)F-FDG imaging followed. Uptake of (11)C-metomidate and (18)F-FDG in incidentalomas was quantified and correlated with the hormonal work-up and the mass size on CT (median, 2.5 cm; range, 2-10 cm). RESULTS: The final diagnoses were hormonally active adenoma (n = 7), nonsecretory adenoma (n = 5), adrenocortical carcinoma (n = 1), pheochromocytoma (n = 2), benign noncortical tumor (n = 2), normal adrenal (n = 1), and malignant noncortical tumor (n = 3). Diagnosis was established at surgery (n = 9), percutaneous biopsy (n = 4), or follow-up (n = 8). The highest uptake of (11)C-metomidate, expressed as standardized uptake value (SUV), was found in adrenocortical carcinoma (SUV = 28.0), followed by active adenomas (median SUV = 12.7), nonsecretory adenomas (median SUV = 12.2), and noncortical tumors (median SUV = 5.7). Patients with adenomas had significantly higher tumor-to-normal-adrenal (11)C-metomidate SUV ratios than did patients with noncortical tumors. (18)F-FDG detected 2 of 3 noncortical malignancies but failed to detect adrenal metastases from renal cell carcinoma. All inactive and most active adenomas were difficult to detect with (18)F-FDG against background activity, whereas both pheochromocytomas and adrenocortical carcinoma showed slightly increased uptake of (18)F-FDG. There was no correlation between uptake of (11)C-metomidate or (18)F-FDG and mass size. CONCLUSION: (11)C-Metomidate is a promising PET tracer to identify incidentalomas of adrenocortical origin. (18)F-FDG should be reserved for patients with a moderate to high likelihood of neoplastic disease.     

Chemotherapy response evaluation with 18F-FDG PET in patients with non-small cell lung cancer.

The aim of this prospective study was to evaluate the value of (18)F-FDG PET for the assessment of chemotherapy response in patients with non-small cell lung cancer. Furthermore, part of the objective of this study was to compare 2 methods to quantify changes in glucose metabolism. METHODS: In 51 patients, dynamic (18)F-FDG PET was performed before and at 5-8 wk into treatment. Simplified methods to measure glucose metabolism (standardized uptake value [SUV]) and quantitative measures (metabolic rate of glucose [MR(Glu)]), derived from Patlak analysis, were evaluated. The overall survival and progression-free survival with respect to MR(Glu) and SUV were calculated using Kaplan-Meier estimates. Fractional changes in tumor glucose use were stratified by the median value and also the predefined EORTC (European Organization for Research and Treatment of Cancer) metabolic response criteria, and criteria applying cutoff levels similar to those of RECIST (Response Evaluation Criteria in Solid Tumors) were evaluated. RESULTS: When stratifying at the median value of DeltaMR(Glu) and DeltaSUV, the difference in overall survival (P = 0.017 for DeltaMR(Glu), P = 0.018 for DeltaSUV) and progression-free survival (P = 0.002 for DeltaMR(Glu), P = 0.0009 for DeltaSUV) was highly significant. When applying the predefined criteria for metabolic response, the cutoff levels as also used for size measurement (RECIST) showed significant differences for DeltaSUV between response categories in progression-free survival (P = 0.0003) as well as overall survival (P = 0.027). CONCLUSION: The degree of chemotherapy-induced changes in tumor glucose metabolism as determined by (18)F-FDG PET is highly predictive for patient outcome, stratifying patients into groups with widely differing overall survival and progression-free survival probabilities. The use of (18)F-FDG PET for therapy monitoring seems clinically feasible, because simplified methods to measure tumor glucose use (SUV) are sufficiently reliable and can replace more complex, quantitative measures (MR(Glu)) in this patient population.     

Anesthesia condition for (18)F-FDG imaging of lung metastasis tumors using small animal PET

Small animal positron emission tomography (PET) with (18)F-FDG has been increasingly used for tumor imaging in the murine model. The aim of this study was to establish the anesthesia condition for imaging of lung metastasis tumor using small animal (18)F-FDG PET. METHODS: To determine the impact of anesthesia on (18)F-FDG distribution in normal mice, five groups were studied under the following conditions: no anesthesia, ketamine and xylazine (Ke/Xy), 0.5% isoflurane (Iso 0.5), 1% isoflurane (Iso 1) and 2% isoflurane (Iso 2). The ex vivo counting, standard uptake value (SUV) image and glucose SUV of (18)F-FDG in various tissues were evaluated. The (18)F-FDG images in the lung metastasis tumor model were obtained under no anesthesia, Ke/Xy and Iso 0.5, and registered with CT image to clarify the tumor region. RESULTS: Blood glucose concentration and muscle uptake of (18)F-FDG in the Ke/Xy group markedly increased more than in the other groups. The Iso 2 group increased (18)F-FDG uptake in heart compared with the other groups. The Iso 0.5 anesthesized group showed the lowest (18)F-FDG uptake in heart and chest wall. The small size of lung metastasis tumor (2 mm) was clearly visualized by (18)F-FDG image with the Iso 0.5 anesthesia. CONCLUSION: Small animal (18)F-FDG PET imaging with Iso 0.5 anesthesia was appropriate for the detection of lung metastasis tumor. To acquire (18)F-FDG PET images with small animal PET, the type and level of anesthetic should be carefully considered to be suitable for the visualization of target tissue in the experimental model.     

Heterogeneity Analysis of 18F-FDG Uptake in Differentiating Between Metastatic and Inflammatory Lymph Nodes in Adenocarcinoma of the Lung: Comparison with Other Parameters and its Application in a Clinical Setting

Purpose

Lymph node (LN) characterization is crucial in determining the stage and treatment decisions in patient with lung cancer. Although ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) has a higher diagnostic accuracy in LN characterization than anatomical imaging, differentiating between metastatic and inflammatory LNs is still challenging because both could show high ¹⁸F-FDG uptake. The purpose of this study was to assess if the heterogeneity of the ¹⁸F-FDG uptake could help in differentiating between inflammatory and metastatic LNs in lung cancer, and to compare with other parameters.

Methods

A total of 44 patients with adenocarcinoma of the lung, who underwent preoperative ¹⁸F-FDG PET/CT without having any previous treatments and were revealed to have ¹⁸F-FDG-avid LNs, were enrolled. There were 52 pathology-proven metastatic lymph nodes in 26 subjects. The pathology-proven metastatic LNs were compared with 42 pathology-proven inflammatory/benign LNs in 18 subjects. The coefficient of variation (CV) was used to assess the heterogeneity of ¹⁸F-FDG uptake by dividing the standard deviation of standardized uptake value (SUV) by mean SUV. The volume of interest was manually drawn based on the combined CT images of ¹⁸F-FDG PET/CT (no threshold is used). Comparisons were made with the maximum standardized uptake values (SUVmax), visual assessment of ¹⁸F-FDG uptake, longest diameter, and maximum Hounsfield units (HUmax).

Results

Metastatic lymph nodes tended to have higher CVs than the inflammatory LNs. The mean CV of metastatic LNs (0.30 ± 0.08; range: 0.08–0.55) was higher than that of inflammatory LNs (0.17 + 0.06; range, 0.07–0.32; P < 0.0001). On receiver operating characteristic (ROC) curve analysis, the area under curve was 0.901, and using 0.20 as cut-off value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 88.5 %, 76.2 %, 82.2 %, 84.3, and 83.0 % respectively. Accuracy of CV was slightly higher than SUVmax and diameter, but significantly higher than visual assessment and HUmax.

Conclusions

In patients with adenocarcinoma of the lung having no prior treatments, metastatic LNs showed more heterogeneous ¹⁸F-FDG uptake than inflammatory LNs. Measuring the CV of the SUV derived from a manual volume of interest (VOI) can be helpful in determining metastatic LN of adenocarcinoma of the lung. Including diagnostic criteria of CV into the diagnostic approach can increase the accuracy of mediastinal node status.     

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.     

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.     

Patterns of FDG uptake in post-thoracotomy surgical scars in patients with lung cancer

Increased (18)F-fluorodeoxyglucose ((18)F-FDG) uptake can occur in surgical scars. This study assesses the incidence, patterns and natural history of (18)F-FDG uptake in post-thoracotomy scars of non-small cell lung cancer (NSCLC) patients. 73 (18)F-FDG-PET/CT studies performed after resection of NSCLC in 61 patients (49 men, 12 women; mean age, 66.7 years) were retrospectively reviewed for the presence, pattern and intensity (maximum standardized uptake value (SUV(max))) of (18)F-FDG uptake in sites of previous thoracotomy. Increased (18)F-FDG uptake in surgical scars was found in 61% of studies (43/70) (average SUV(max), 3.6); 3 patients with recurrence at the surgical scar were excluded from the analysis of the characteristics of physiological FDG uptake in scars over time. The average time from surgery was 14.4 months in patients with, and 43.8 months in patients without, scar uptake (p<0.0002). Increased uptake was seen in 14/14 studies (100%) at 1-3 months, in 12/13 studies (92%) at 3-12 months, and in 17/43 studies (40%) at more than 12 months after surgery in patients with no evidence of disease on follow-up. (18)F-FDG uptake was diffuse in 67% of studies (29/43). Tumour recurrence in the scar was found in three studies, showing focally increased uptake (average SUV(max), 9.1 ) at 3-8 months after thoracotomy. In conclusion, increased (18)F-FDG uptake in post-thoracotomy surgical scars is mainly diffuse, and decreases in incidence and intensity with time, with 60% of studies showing no scar uptake at more than 12 months after surgery. Focally intense scar uptake should be evaluated for suspected recurrence.     

氩氦刀冷冻消融术后PET/CT的标准化摄取值与肿瘤残存的相关性研究

目的 探讨肿瘤氩氦刀冷冻消融术后18F-FDG PET/CT显像的标准化摄取值(SUV)与肿瘤残存的相关性.方法 收集2008年3月至2015年12月40例肝、肺恶性肿瘤氩氦刀冷冻消融治疗患者的临床资料,治疗前后行18F-FDG PET/CT检查,记录每例患者的SUV值,并根据病理和临床随访进行数据分析.结果 40例患者共42个治疗灶,38个病灶术后发现放射性核素浓聚,经影像学随访和病理检查证实16个病灶有肿瘤残存,22个病灶为炎性反应.肿瘤残存病灶的SUV值明显高于炎性反应(6.13±1.21对2.64±0.96,P＜0.05),低SUV值组具有较低的复发率(P=0.020)和较高的生存率(P=0.039).低SUV值组的肿瘤残存率明显低于高SUV值组(x2=14.994,P=0.000 2).结论 18F-FDG PET/CT显像在冷冻消融术后边缘残余病灶的及时检出方面具有独特价值,为判断消融效果和进一步的临床治疗提供依据.