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.     

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.     

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.     

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.     

Comparison of tumor volumes derived from glucose metabolic rate maps and SUV maps in dynamic 18F-FDG PET.

Tumor delineation using noninvasive medical imaging modalities is important to determine the target volume in radiation treatment planning and to evaluate treatment response. It is expected that combined use of CT and functional information from 18F-FDG PET will improve tumor delineation. However, until now, tumor delineation using PET has been based on static images of 18F-FDG standardized uptake values (SUVs). 18F-FDG uptake depends not only on tumor physiology but also on blood supply, distribution volume, and competitive uptake processes in other tissues. Moreover, 18F-FDG uptake in tumor tissue and in surrounding healthy tissue depends on the time after injection. Therefore, it is expected that the glucose metabolic rate (MRglu) derived from dynamic PET scans gives a better representation of the tumor activity than does SUV. The aim of this study was to determine tumor volumes in MRglu maps and to compare them with the values from SUV maps. METHODS: Twenty-nine lesions in 16 dynamic 18F-FDG PET scans in 13 patients with non-small cell lung carcinoma were analyzed. MRglu values were calculated on a voxel-by-voxel basis using the standard 2-compartment 18F-FDG model with trapping in the linear approximation (Patlak analysis). The blood input function was obtained by arterial sampling. Tumor volumes were determined in SUV maps of the last time frame and in MRglu maps using 3-dimensional isocontours at 50% of the maximum SUV and the maximum MRglu, respectively. RESULTS: Tumor volumes based on SUV contouring ranged from 1.31 to 52.16 cm3, with a median of 8.57 cm3. Volumes based on MRglu ranged from 0.95 to 37.29 cm3, with a median of 3.14 cm3. For all lesions, the MRglu volumes were significantly smaller than the SUV volumes. The percentage differences (defined as 100% x (V MRglu - V SUV)/V SUV, where V is volume) ranged from -12.8% to -84.8%, with a median of -32.8%. CONCLUSION: Tumor volumes from MRglu maps were significantly smaller than SUV-based volumes. These findings can be of importance for PET-based radiotherapy planning and therapy response monitoring.     

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.     

Early prediction of response to chemotherapy in metastatic breast cancer using sequential 18F-FDG PET.

Chemotherapy is currently the treatment of choice for patients with high-risk metastatic breast cancer. Clinical response is determined after several cycles of chemotherapy by changes in tumor size as assessed by conventional imaging procedures including CT, MRI, plain film radiography, or ultrasound. The aim of this study was to evaluate the use of sequential 18F-FDG PET to predict response after the first and second cycles of standardized chemotherapy for metastatic breast cancer. METHODS: Eleven patients with 26 metastatic lesions underwent 31 (18)F-FDG PET examinations (240-400 MBq of 18F-FDG; 10-min 2-dimensional emission and transmission scans). Clinical response, as assessed by conventional imaging after completion of chemotherapy, served as the reference. 18F-FDG PET images after the first and second cycles of chemotherapy were analyzed semiquantitatively for each metastatic lesion using standardized uptake values (SUVs) normalized to patients' blood glucose levels. In addition, whole-body 18F-FDG PET images were viewed for overall changes in the 18F-FDG uptake pattern of metastatic lesions within individual patients and compared with conventional imaging results after the third and sixth cycles of chemotherapy. RESULTS: After completion of chemotherapy, 17 metastatic lesions responded, as assessed by conventional imaging procedures. In those lesions, SUV decreased to 72% +/- 21% after the first cycle and 54% +/- 16% after the second cycle, when compared with the baseline PET scan. In contrast, 18F-FDG uptake in lesions not responding to chemotherapy (n = 9) declined only to 94% +/- 19% after the first cycle and 79% +/- 9% after the second cycle. The differences between responding and nonresponding lesions were statistically significant after the first (P = 0.02) and second (P = 0.003) cycles. Visual analysis of 18F-FDG PET images correctly predicted the response in all patients as early as after the first cycle of chemotherapy. As assessed by 18F-FDG PET, the overall survival in nonresponders (n = 5) was 8.8 mo, compared with 19.2 mo in responders (n = 6). CONCLUSION: In patients with metastatic breast cancer, sequential 18F-FDG PET allowed prediction of response to treatment after the first cycle of chemotherapy. The use of 18F-FDG PET as a surrogate endpoint for monitoring therapy response offers improved patient care by individualizing treatment and avoiding ineffective chemotherapy.     

Is 18F-3'-fluoro-3'-deoxy-L-thymidine useful for the staging and restaging of non-small cell lung cancer?

The objective of this study was to compare 18F-3'-fluoro-3'-deoxy-L-thymidine (FLT) PET with clinical TNM staging, including that by 18F-FDG PET, in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with NSCLC underwent whole-body 18F-FDG PET and whole-body 18F-FLT PET, using a median of 360 MBq of 18F-FDG (range, 160-500 MBq) and a median of 210 MBq of 18F-FLT (range, 130-420 MBq). 18F-FDG PET was performed 90 min after 18F-FDG injection, and 18F-FLT PET was performed 60 min after 18F-FLT injection. Two viewers independently categorized the localization and intensity of tracer uptake for all lesions. All 18F-FDG PET and 18F-FLT PET lesions were compared. Staging with 18F-FLT PET was compared with clinical TNM staging based on the findings of history, physical examination, bronchoscopy, CT, and 18F-FDG PET. From 8 patients, standardized uptake values (SUVs) were calculated. Maximal SUV and mean SUV were calculated. RESULTS: Sixteen patients with stage IB-IV NSCLC and 1 patient with strong suspicion of NSCLC were investigated. Sensitivity on a lesion-by-lesion basis was 80% for the 8 patients who received treatment before 18F-FLT PET and 27% for the 9 patients who did not receive pretreatment, using 18F-FDG PET as the reference standard. Compared with clinical TNM staging, staging by 18F-FLT PET was correct for 8 of 17 patients: 5 of 9 patients in the group with previous therapy and 3 of 8 patients in the group without previous therapy. The maximal SUV of 18F-FLT PET, at a median of 2.7 and range of 0.8-4.5, was significantly lower than that of 18F-FDG PET, which had a median of 8.0 and range of 3.7-18.8 (n = 8; P = 0.012). The mean SUV of 18F-FLT PET, at a median of 2.7 and range of 1.4-3.3, was significantly lower than that of 18F-FDG PET, which had a median of 6.2 and range of 2.8-13.9 (n = 6; P = 0.027). CONCLUSION: 18F-FLT PET is not useful for staging and restaging NSCLC.     

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.     

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.     

18F-FDG uptake by primary tumor as a predictor of intratumoral lymphatic vessel invasion and lymph node involvement in non-small cell lung cancer: analysis of a multicenter study.

Intratumoral lymphatic vessel invasion and lymph node involvement are important factors in the planning of therapeutic strategies, particularly limited surgical resection in patients with non-small cell lung cancer. (18)F-FDG uptake within the primary lesion correlates with aggressiveness on PET studies. The more metabolically active the tumor, the more aggressive are the findings. The aim of this multicenter study was to determine whether (18)F-FDG uptake of the primary tumor is a predictor of intratumoral lymphatic vessel invasion and lymph node metastasis in patients with non-small cell lung cancer. METHODS: One hundred thirty-two patients with lung cancer were studied. All patients underwent a thoracotomy within 4 wk of the (18)F-FDG PET study. A 3-point visual scoring system (low, moderate, or high grade in comparison with mediastinal activity) was used to interpret (18)F-FDG uptake within the primary lesions. The degree of (18)F-FDG uptake in the primary tumor was correlated with the incidence of intratumoral lymphatic vessel invasion and lymph node involvement. Multivariate analysis was performed with logistic multivariate analysis to assess the joint effects and interactions of the variables (age, sex, tumor size, histology, and (18)F-FDG uptake) on intratumoral lymphatic vessel invasion and lymph node involvement. RESULTS: Intratumoral lymphatic vessel invasion and lymph node involvement were found in 7.1% and 5.9%, respectively, of the patients classified in the low-grade group, and in 14.3% and 10.0%, respectively, of the patients classified in the moderate-grade group. In contrast, of the patients classified in the group with high (18)F-FDG uptake, intratumoral lymphatic vessel invasion and lymph node involvement were found in 39.7% and 38.9%, respectively. Multivariate analysis showed that only (18)F-FDG uptake was a significant factor for intratumoral lymphatic vessel invasion and that tumor size and (18)F-FDG uptake were significant factors for lymph node involvement. Of the patients in the high-grade group whose tumors were classified as > or =3 cm in size, lymph node involvement was found in 51.5%. In contrast, of the patients in the low- to moderate-grade group whose tumors were classified as <3 cm in size, lymph node involvement was found in only 9.1% (P < 0.0001). CONCLUSION: Patients with a low to moderate (18)F-FDG uptake in the primary lesion had a significantly lower risk of concurrent intratumoral lymphatic vessel invasion and nodal involvement than did patients with a high (18)F-FDG uptake. In patients with non-small cell lung cancer, (18)F-FDG uptake by the primary tumor is a strong predictor of intratumoral lymphatic vessel invasion and lymph node metastasis.     

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.     

术前18F-FDG PET/CT显像代谢参数在非小细胞肺癌患者预后评估中的应用进展

肺癌是目前世界上最常见的癌症之一,在所有的恶性肿瘤中,肺癌的病死率高居榜首,而非小细胞肺癌（NSCLC）约占所有肺癌的85%。18F-氟脱氧葡萄糖（FDG）PET/CT作为一种从分子水平反映肿瘤细胞代谢状态的功能显像方法,已成为NSCLC诊断、分期和疗效评价的重要工具。18F-FDG PET/CT可检测出常规CT遗漏的其他病变部位,在肺癌患者的手术切除预后方面起着越来越重要的作用。笔者就18F-FDG PET/CT相关代谢参数在预测可手术切除NSCLC患者预后方面的应用进展进行综述。     

Findings on 18F-FDG PET scans after neoadjuvant chemoradiation provides prognostic stratification in patients with locally advanced rectal carcinoma subsequently treated by radical surgery.

Predicting outcome after aggressive therapy for advanced rectal cancer remains difficult. (18)F-FDG PET has emerged as a valid method for predicting patient outcomes after therapy in an increasing number of cancers. We evaluated the prognostic information obtained from the degree of change in tumor (18)F-FDG PET uptake induced by chemoradiation before radical curative surgery in patients with T3/T4 rectal cancer. METHODS: The study included 34 consecutive patients with T3/T4 Nx M0 rectal cancer on structural imaging, who underwent staging and postchemoradiation (18)F-FDG PET before planned curative surgery. Change in (18)F-FDG uptake was graded visually as complete (CMR), partial (PMR), or no (NoMR) metabolic response. Pre- and postchemoradiation (18)F-FDG PET-derived standardized uptake values (SUVs) were then obtained for PMR patients to determine whether SUV further stratified this subgroup. Operative findings were available in 30 patients (3 excluded because of (18)F-FDG PET-defined M1 disease, 1 refused surgery). Clinical status at study closeout (alive free from disease, FFD; alive with disease, AWD; or died of disease, DOD) was available for all patients. RESULTS: A pathologic complete response was found in only 6 of 30 patients (5 CMR, 1 false-positive PMR). However, after an estimated median 3.1 y of follow-up, all 17 CMR patients were FFD, 6 of 10 PMR patients were FFD, 2 of 10 had DOD, and 2 of 10 were AWD. All 3 NoMR patients DOD. PET response was highly significantly associated with overall survival duration (P < 0.0001) and time to progression (P < 0.0001). Pathologic complete response was the only other statistically significant prognostic factor (P < 0.03). The percentage of maximum SUV change after chemoradiation was not predictive of survival in PMR patients. CONCLUSION: Using a simple qualitative assessment, postchemoradiation (18)F-FDG PET scintigraphy provides good medium-term prognostic information in patients with advanced rectal cancer undergoing radical surgery with curative intent.     

18F-FDG PET显像在乳腺癌中的应用

^18F-FDG(^18F-氟脱氧葡萄糖)PET(正电子发射型计算断层显像)是反映恶性肿瘤代谢特征的一种无创性的功能显像方法。在绝大多数肿瘤中均得到广泛应用。本文通过对国内外乳腺癌^18F-FDG PET。显像的文章进行全面综合分析，旨在探讨^18F-FDG PET显像在乳腺癌中的应用原理及其临床应用价值。与传统影像学相比，^18F-FDG PET。显像能够更为准确地发现原发性乳腺癌远处转移和局部复发，可以在治疗早期及时评价化疗疗效以指导临床治疗。对于原发性乳腺癌的诊断。PET显像不作为首选检查。但对于临床检查或常规影像检查难以进行或无明确结论的病人。PET显像可以作为其乳腺肿块定性诊断的最佳选择。     

The role of 18F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are gaining the interest of researchers because of impressive metabolic response to the targeted molecular therapeutic drug imatinib mesylate. Initial reports suggest an impressive role for (18)F-FDG PET in follow-up of therapy for these tumors. However, the role of (18)F-FDG PET versus that of CT has not been established. Therefore, we compared the roles of (18)F-FDG PET and CT in staging and evaluation of early response to imatinib mesylate therapy in recurrent or metastatic GIST. METHODS: The study included 54 patients who underwent (18)F-FDG PET and CT scans within 3 wk before initiation of imatinib mesylate therapy. Forty-nine of these patients underwent repeat scans 2 mo after therapy. The numbers of sites or organs containing lesions on (18)F-FDG PET and CT scans were compared. Corresponding lesions on (18)F-FDG PET and CT scans or those confirmed to be malignant in appearance by other imaging modalities or on follow-up were considered true positives. Lesions seen on (18)F-FDG PET or CT scans but not seen or confirmed to be of benign appearance with other imaging modalities or on follow-up were considered false positives. Measurements of the maximum standard uptake value (SUV) on (18)F-FDG PET scans and tumor size on CT scans were used for quantitative evaluation of early tumor response to therapy. RESULTS: A total of 122 and 114 sites and/or organs were involved on pretherapy (18)F-FDG PET and CT scans, respectively. The sensitivity and positive predictive values (PPVs) for CT were 93% and 100%; whereas these values for (18)F-FDG PET were 86% and 98%. However, the differences between these values for CT and (18)F-FDG PET were not statistically significant (P = 0.27 for sensitivity and 0.25 for PPV). This suggests comparable performance of (18)F-FDG PET and CT in staging GISTs. Repeat scans at 2 mo after therapy showed agreement between (18)F-FDG PET and CT scans in 71.4% of patients (57.1% having a good response to therapy and 14.3% lacking a response). Discrepant results between (18)F-FDG PET and CT were recorded for 28.6% of the patients. (18)F-FDG PET predicted response to therapy earlier than did CT in 22.5% of patients during a longer follow-up interval (4-16 mo), whereas CT predicted lack of response to therapy earlier than (18)F-FDG PET in 4.1%. One patient did not undergo long-term follow-up. These findings suggest that (18)F-FDG PET is superior to CT in predicting early response to therapy in recurrent or metastatic GIST patients. CONCLUSION: The performances of (18)F-FDG PET and CT are comparable in staging GISTs before initiation of imatinib mesylate therapy. However, (18)F-FDG PET is superior to CT in predicting early response to therapy. Thus, (18)F-FDG PET is a better guide for imatinib mesylate therapy.     

Spatial and temporal heterogeneity of regional myocardial uptake in patients without heart disease under fasting conditions on repeated whole-body 18F-FDG PET/CT.

Imaging of cardiac (18)F-FDG uptake is used in the diagnostic evaluation of residual viable myocardium. Although, originally, hibernating myocardium was identified by a mismatch between perfusion defect and relatively preserved (18)F-FDG uptake, at present several studies propose that (18)F-FDG distribution can also be used alone for this purpose. Nevertheless, even severe myocardial (18)F-FDG uptake defects are frequently observed in cancer patients without any cardiac disease. The aim of this study was to retrospectively analyze global and regional (18)F-FDG cardiac images of 49 consecutive cancer patients free of cardiac diseases who submitted to 3 PET scans under fasting conditions. METHODS: Images were acquired with a high-resolution PET/CT scanner. Three-dimensional regions of interest were drawn on the fused PET/CT images to measure the maximal standardized uptake value of the left ventricular myocardium (SUV(Myo)) as well as the average SUV of the left ventricular blood (SUV(LV)) and of the liver (SUV(Liver)). Analysis of regional myocardial (18)F-FDG uptake was performed on a subsample of 26 patients by an automatic recognition of endocardial and epicardial borders and subdividing the left ventricle in 20 segments. Regional (18)F-FDG distribution was defined as the percentage of SUV(Myo) in each region. RESULTS: SUV(Myo) as well as SUV(LV) and SUV(Liver) did not change on average throughout the studies. This stability was not caused by a persistent pattern of myocardial (18-)FDG distribution. Rather, it was associated with important variations in both directions over time. Regional (18)F-FDG distribution was largely heterogeneous in all 3 studies, with a variation coefficient in each patient of 18% +/- 7%, 18% +/- 5%, and 17% +/- 5%, respectively. An (18)F-FDG uptake of <50% occurred in 78, 102, and 69 of 468 segments, although it disappeared in 55% of instances at subsequent examinations. Regional temporal variability was also marked: The absolute value of the difference in percent uptake was 10.1% +/- 7.3% from test 1 to test 2, 8.0% +/- 7.0% from test 1 to test 3, and 9.2% +/- 6.9% from test 2 to test 3. Overall from one test to another, uptake increased or decreased by >10% in 76 and in 116 of 468 segments, respectively. CONCLUSION: The large spatial and temporal heterogeneity of the myocardial metabolic pattern, in cancer patients free of any disease, suggests a word of caution on the use of (18)F-FDG alone as a diagnostic tool for myocardial viability.     

Monitoring isotretinoin therapy in thyroid cancer using 18F-FDG PET

Treatment with isotretinoin (13-cis-retinoic acid, 13-cis-RA) is a recent additional option in advanced, otherwise intractable differentiated thyroid cancers. The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the prediction and the monitoring of response to 13-cis-RA therapy. Twenty-one patients with advanced differentiated thyroid cancers were investigated using 18F-FDG PET and iodine-131 whole-body scans before and 3, 6 and 9 months after initiation of 13-cis-RA therapy. After 9 months, 13-cis-RA treatment was discontinued and imaging procedures repeated 3 months later. Average 18F-FDG uptake (SUV) decreased significantly during 13-cis-RA therapy but subsequently increased in five of eight patients after withdrawal of 13-cis-RA. 18F-FDG uptake (SUV) 3 months after onset of 13-cis-RA therapy was significantly lower in patients who developed increased 131I uptake in their tumour sites than in patients with no subsequent increase in 131I uptake. There was no relationship between serum thyroglobulin level on the one hand and simultaneously measured 131I or 18F-FDG uptake on the other hand. There was a tendency towards lower 18F-FDG uptake in tumour manifestations with a better outcome. Therefore, 18F-FDG PET at 3 months after the start of treatment promises to differentiate between those patients who will eventually benefit from 13-cis-RA and those who will not. In conclusion, these data indicate that 18F-FDG PET is a useful tool for the evaluation and monitoring of adjuvant therapy with 13-cis-RA in thyroid cancer.     

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。     

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.