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.     

Dynamic PET 18F-FDG studies in patients with primary and recurrent soft-tissue sarcomas: impact on diagnosis and correlation with grading.

The purpose of this study was to evaluate (18)F-FDG PET studies of primary and recurrent sarcomas for diagnosis and correlation with grading. METHODS: The evaluation included 56 patients, 43 with histologically proven malignancies and 13 with benign lesions. Seventeen patients were referred with suspicion on a primary tumor, and the remaining 39 were referred with suspicion on a recurrent tumor. The FDG studies were accomplished as a dynamic series for 60 min. The evaluation of the FDG kinetics was performed using the following parameters: standardized uptake value (SUV), global influx, computation of the transport constants K1-k4 with consideration of the distribution volume (VB) according to a two-tissue-compartment model, and fractal dimension based on the box-counting procedure (parameter for the inhomogeneity of the tumors). RESULTS: Visual evaluation revealed a sensitivity of 76.2%, a specificity of 42.9%, and an accuracy of 67.9%. The vascular fraction VB and the SUV were higher in malignant tumors compared with benign lesions (t test, P < 0.05). Although the FDG SUV helped to distinguish benign and malignant tumors, there was some overlap, which limited the diagnostic accuracy. The SUV and fractal dimension accounted for significant differences in six of the nine diagnostic pairs. Whereas grade (G) II and G III tumors were differentiated from lipomas on the basis of the fractal dimension and some other kinetic parameters, no differences were found between G I tumors and lipomas. On the basis of the discriminant analysis, the differentiation of soft-tissue tumors was best for the use of six parameters of the FDG kinetics (SUV, VB, K1, k3, influx, and fractal dimension). Eighty-four percent of G III tumors, 37.5% of G II tumors, 80% of G I tumors, 50% of lipomas, and 14.3% of scars could be classified correctly, whereas inflammatory lesions were misclassified. CONCLUSION: FDG PET should be used preferentially for monitoring patients with G III sarcomas. Visual analysis provides a low specificity. In contrast, the evaluation of the full FDG kinetics provides superior information, particularly for the discrimination of G I and G III tumors (positive predictive value, >80%).     

The role of quantitative (18)F-FDG PET studies for the differentiation of malignant and benign bone lesions.

The role of quantitative (18)F-FDG PET studies for the differentiation of benign and malignant bone lesions is still an open question. METHODS: Our evaluation included 83 patients with 37 histologically proven malignancies and 46 benign lesions. Thirty-five of the 46 benign lesions were histologically confirmed. The (18)F-FDG studies were accomplished as a dynamic series for 60 min. Evaluation of the (18)F-FDG kinetics was performed using the following parameters: standardized uptake value (SUV), global influx (Ki), computation of the transport constants K1-k4 with consideration of the distribution volume (VB) according to a 2-tissue-compartment model, fractal dimension based on the box-counting procedure (parameter for the inhomogeneity of the tumors). RESULTS: The mean SUV, the vascular fraction VB, K1, and k3 were higher in malignant tumors compared with benign lesions (t test; P < 0.05). Although the (18)F-FDG SUV was helpful to differentiate benign and malignant tumors, there was some overlap, which limited the diagnostic accuracy. On the basis of the discriminant analysis, the SUV alone showed a sensitivity of only 54.05%, a specificity of 91.30%, and a diagnostic accuracy of 74.70%. The fractal dimension was superior and showed a sensitivity of 71.88%, a specificity of 81.58%, and an accuracy of 77.14%. The combination of SUV, fractal dimension, VB, K1-k4, and Ki revealed the best results with a sensitivity of 75.86%, a specificity of 97.22%, and an accuracy of 87.69%. Bayesian analysis showed true-positive results at the level of 0.8 for a low prevalence of disease (0.235) if the full kinetic data were used in the evaluation. CONCLUSION: (18)F-FDG PET has a high specificity for the exclusion of a malignant bone tumor. Evaluation of the full (18)F-FDG kinetics and the application of discriminant analysis are required and can be used prospectively to classify a bone lesion as malignant or benign.     

Focal thyroid lesions incidentally identified by integrated 18F-FDG PET/CT: clinical significance and improved characterization.

In this retrospective study, we investigated whether the (18)F-FDG uptake pattern and CT findings improved the accuracy over the standardized uptake value (SUV) for differentiating benign from malignant focal thyroid lesions incidentally found on (18)F-FDG PET/CT. We also defined the prevalence of these lesions and their risk for cancer. METHODS: (18)F-FDG PET/CT was performed on 1,763 subjects without a previous history of thyroid cancer from May 2003 to June 2004. Two nuclear medicine physicians and 1 radiologist interpreted PET/CT images, concentrating on the presence of focal thyroid lesions, the maximum SUV of the thyroid lesion, the pattern of background thyroid (18)F-FDG uptake, and the CT attenuation pattern of the thyroid lesion. RESULTS: The prevalence of focal thyroid lesions on PET/CT was 4.0% (70/1,763). Diagnostic confirmation was done on 44 subjects by ultrasonography (US)-guided fine-needle aspiration (n = 29) or US with clinical follow-up (n = 15). Among 49 focal thyroid lesions in these 44 subjects, 18 focal thyroid lesions of 17 subjects were histologically proven to be malignant (papillary cancer in 16, metastasis from esophageal cancer in 1, non-Hodgkin's lymphoma in 1). Therefore, the cancer risk of focal thyroid lesions was 36.7% on a lesion-by-lesion basis or 38.6% on a subject-by-subject basis. The maximum SUV of malignant thyroid lesions was significantly higher than that of benign lesions (6.7 +/- 5.5 vs. 10.7 +/- 7.8; P < 0.05). When only the maximum SUV was applied to differentiate benign from malignant focal thyroid lesions for the receiver-operating-characteristic curve analysis, the area under the curve (AUC) of PET was 0.701. All 16 focal thyroid lesions with very low attenuation or nonlocalization on CT images, or with accompanying diffusely increased thyroid (18)F-FDG uptake, were benign. When those lesions were regarded as benign lesions, irrespective of the maximum SUV, the AUC of PET/CT was significantly improved to 0.878 (P < 0.01). CONCLUSION: Focal thyroid lesions incidentally found on (18)F-FDG PET/CT have a high risk of thyroid malignancy. Image interpretation that includes (18)F-FDG uptake and the CT attenuation pattern, along with the SUV, significantly improves the accuracy of PET/CT for differentiating benign from malignant focal thyroid lesions.     

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.     

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.     

Accuracy of PET for diagnosis of solid pulmonary lesions with 18F-FDG uptake below the standardized uptake value of 2.5.

Benign and malignant pulmonary lesions usually are differentiated by 18F-FDG PET with a semiquantitative 18F-FDG standardized uptake value (SUV) of 2.5. However, the frequency of malignancies with an SUV of <2.5 is significant, and pulmonary nodules with low 18F-FDG uptake often present diagnostic challenges. METHODS: Among 360 consecutive patients who underwent 18F-FDG PET to evaluate pulmonary nodules found on CT, we retrospectively analyzed 43 who had solid pulmonary lesions (excluding lesions with ground-glass opacity, infiltration, or benign calcification) with an SUV of <2.5. The uptake of 18F-FDG was graded by a visual method (absent, faint, moderate, or intense) and 2 semiquantitative methods (SUV and contrast ratio [CR]). Final classification was based on histopathologic findings or at least 6 mo of clinical follow-up. RESULTS: We found 16 malignant (diameter, 8-32 mm) and 27 benign (7-36 mm) lesions. When faint visual uptake was the cutoff for positive 18F-FDG PET results, the receiver-operating-characteristic (ROC) analysis correctly identified all 16 malignancies and yielded false-positive results for 10 of 27 benign lesions. Sensitivity was 100%, specificity was 63%, and the positive and negative predictive values were 62% and 100%, respectively. When an SUV of 1.59 was the cutoff for positive 18F-FDG PET results, the ROC analysis revealed 81% sensitivity, 85% specificity, and positive and negative predictive values of 77% and 89%, respectively. At a cutoff for positive 18F-FDG PET results of a CR of 0.29, the ROC analysis revealed 75% sensitivity, 82% specificity, and positive and negative predictive values of 71% and 85%, respectively. The areas under the curve in ROC analyses did not differ significantly among the 3 analyses (visual, 0.84; SUV, 0.81; and CR, 0.82). Analyses of intra- and interobserver variabilities indicated that visual and SUV analyses were quite reproducible, whereas CR analysis was poorly reproducible. CONCLUSION: These results suggested that for solid pulmonary lesions with low 18F-FDG uptake, semiquantitative approaches do not improve the accuracy of 18F-FDG PET over that obtained with visual analysis. Pulmonary lesions with visually absent uptake indicate that the probability of malignancies is very low. In contrast, the probability of malignancy in any visually evident lesion is about 60%.     

Dual-time-point 18F-FDG PET for the evaluation of gallbladder carcinoma.

Conventional imaging techniques such as ultrasonography, CT, and MRI are able to detect gallbladder abnormalities but are not always able to differentiate a malignancy from other disease processes such as cholecystitis. The purpose of the present study was to evaluate the efficacy of dual-time-point (18)F-FDG PET for differentiating malignant from benign gallbladder disease. METHODS: The study evaluated 32 patients who were suspected of having gallbladder tumors. (18)F-FDG PET (whole body) was performed at 62 +/- 8 min (early) after (18)F-FDG injection and was repeated 146 +/- 14 min (delayed) after injection only in the abdominal region. We evaluated the (18)F-FDG uptake both visually and semiquantitatively. Semiquantitative analysis using the standardized uptake value (SUV) was performed for both early and delayed images (SUV(early) and SUV(delayed), respectively). The retention index (RI) was calculated according to the equation (SUV(delayed) - SUV(early)) x 100/SUV(early). The tumor-to-liver ratio was also calculated. Results: The final diagnosis was gallbladder carcinoma in 23 patients and benign disease in 9 patients. For visual analysis of gallbladder carcinoma, delayed (18)F-FDG PET images improved the specificity of diagnosis in 2 patients. When an SUV(early) of 4.5, SUV(delayed) of 2.9, and RI of -8 were chosen as arbitrary cutoffs for differentiating between malignant and benign conditions, sensitivity increased from 82.6% to 95.7% and 100% for delayed imaging and combined early and delayed imaging (i.e., RI), respectively. With the same criteria, specificity decreased from 55.6% to 44.4% for delayed imaging and combined early and delayed imaging, respectively. The specificity of (18)F-FDG PET improved to 80% in the group with a normal level of C-reactive protein (CRP) and decreased to 0% in the group with an elevated CRP level. For gallbladder carcinoma, both SUV and tumor-to-liver ratios derived from delayed images were significantly higher than the ratios derived from early images (P < 0.0001). CONCLUSION: Delayed (18)F-FDG PET is more helpful than early (18)F-FDG PET for evaluating malignant lesions because of increased lesion uptake and increased lesion-to-background contrast. However, the diagnostic performance of (18)F-FDG PET depends on CRP levels.     

双时相18F-FDG PET显像用于肿瘤良恶性鉴别诊断

目的探讨双时相^18F-FDG PET显像在肿瘤良恶性鉴别中的临床价值。方法52例单次显像难以鉴别病变性质的患者行双时相全身^18 F-FDG PET／CT显像，将显像结果与病理学检查结果对照。结果43例延迟显像SUV升高的患者中有39例经病理检查证实为恶性病变，4例为良性病变；9例延迟显像SUV降低的患者中有7例经病理检查证实为良性病变，2例为恶性病变。灵敏度为95．1％，准确性为88．5％，特异性为63．6％，阳性预测值为90．7％，阴性预测值为7／9例。结论双时相^18F—FDG PET对良恶性病变的鉴别具有较高的灵敏度和准确性。     

Diagnostic accuracy of 18F-FDG PET in restaging patients with medullary thyroid carcinoma and elevated calcitonin levels.

Medullary thyroid carcinoma (MTC) is a rare endocrine tumor arising from the C-cells of the thyroid gland. Calcitonin is the principal serum tumor marker. A rising calcitonin level after total thyroidectomy for localized disease generally indicates residual, recurrent, or metastatic disease. The role of (18)F-FDG PET in MTC remains somewhat unclear. We reviewed our own experience with (18)F-FDG PET in postthyroidectomy MTC patients with elevated calcitonin. METHODS: From our database, we identified patients with suspected residual, recurrent, or metastatic MTC and elevated calcitonin who had been referred for (18)F-FDG PET between January 2000 and October 2005. (18)F-FDG PET findings were classified as positive or negative on the basis of visual interpretation of the scan. Standardized uptake values (SUVs) were also calculated. The (18)F-FDG PET findings were verified by histopathologic examination, when available, or other imaging studies and clinical follow-up. Any negative (18)F-FDG PET result was considered false-negative. RESULTS: Twenty-eight patients underwent a total of 38 (18)F-FDG PET studies. Calcitonin levels ranged from 106 to 541,000 pg/mL (median, 7,260 pg/mL). There were 23 true-positive, 1 false-positive, and 14 false-negative (18)F-FDG PET scans, yielding an overall sensitivity of 62%. There was no true-positive finding when calcitonin levels were below 509 pg/mL (n = 5). Using an arbitrary cutoff of 1,000 pg/mL, we found that the sensitivity in scans with calcitonin levels greater than 1,000 pg/mL increased to 78% (21/27; 95% confidence interval, 58%-91%). The mean SUV of all lesions with (18)F-FDG uptake was 5.3 +/- 3.2 (range, 2.0-15.9). Among the 14 patients with false-negative (18)F-FDG PET findings, 8 had concurrent anatomic imaging studies and only 2 of these had positive findings. CONCLUSION: (18)F-FDG PET can detect residual, recurrent, or metastatic MTC with a reasonable sensitivity of 78% when the calcitonin level is above 1,000 pg/mL but appears of limited use if the calcitonin level is below 500 pg/mL.     

18F-FDG PET/CT in the evaluation of adrenal masses.

Our purpose was to evaluate the performance of (18)F-FDG PET/CT, using data from both the PET and the unenhanced CT portions of the study, in characterizing adrenal masses in oncology patients. METHODS: One hundred seventy-five adrenal masses in 150 patients referred for (18)F-FDG PET/CT were assessed. Final diagnosis was based on histology (n = 6), imaging follow-up (n = 118) of 6-29 mo (mean, 14 mo), or morphologic imaging criteria (n = 51). Each adrenal mass was characterized by its size; its attenuation on CT, expressed by Hounsfield units (HU); and the intensity of (18)F-FDG uptake, expressed as standardized uptake value (SUV). Receiver operating characteristic curves were drawn to determine the optimal cutoff values of HU and SUV that would best discriminate between benign and malignant masses. RESULTS: When malignant lesions were compared with adenomas, PET data alone using an SUV cutoff of 3.1 yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 98.5%, 92%, 89.3%, 98.9%, respectively. For combined PET/CT data, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 98%, 97%, 100%, respectively. Specificity was significantly higher for PET/CT (P < 0.01). Fifty-one of the 175 masses were 1.5 cm or less in diameter. When a cutoff SUV of 3.1 was used for this group, (18)F-FDG PET/CT correctly classified all lesions. CONCLUSION: (18)F-FDG PET/CT improves the performance of (18)F-FDG PET alone in discriminating benign from malignant adrenal lesions in oncology patients.     

18F-FDG accumulation with PET for differentiation between benign and malignant lesions in the thorax.

Recent reports have indicated the value and limitations of (18)F-FDG PET and (201)Tl SPECT for determination of malignancy. We prospectively assessed and compared the usefulness of these scintigraphic examinations as well as (18)F-FDG PET delayed imaging for the evaluation of thoracic abnormalities. METHODS: Eighty patients with thoracic nodular lesions seen on chest CT images were examined using early and delayed (18)F-FDG PET and (201)Tl-SPECT imaging within 1 wk of each study. The results of (18)F-FDG PET and (201)Tl SPECT were evaluated and compared with the histopathologic diagnosis. RESULTS: Fifty of the lesions were histologically confirmed to be malignant, whereas 30 were benign. On (18)F-FDG PET, all malignant lesions showed higher standardized uptake value (SUV) levels at 3 than at 1 h, and benign lesions revealed the opposite results. Correlations were seen between (18)F-FDG PET imaging and the degree of cell differentiation in malignant tumors. No significant difference in accuracy was found between (18)F-FDG PET single-time-point imaging and (201)Tl SPECT for the differentiation of malignant and benign thoracic lesions. However, the retention index (RI) of (18)F-FDG PET (RI-SUV) significantly improved the accuracy of thoracic lesion diagnosis. Furthermore, (18)F-FDG PET delayed imaging measuring RI-SUV metastasis was useful for diagnosing nodal involvement and it improved the specificity of mediastinal staging. CONCLUSION: No significant difference was found between (18)F-FDG PET single-time-point imaging and (201)Tl SPECT for the differentiation of malignant and benign thoracic lesions. The RI calculated by (18)F-FDG PET delayed imaging provided more accurate diagnoses of lung cancer.     

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.     

Increased (18)F-fluorodeoxyglucose uptake in benign, nonphysiologic lesions found on whole-body positron emission tomography/computed tomography (PET/CT): accumulated data from four years of experience with PET/CT

The use of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) in the field of oncology is rapidly evolving; however, (18)F-FDG is not tumor specific. Aside from physiological uptake (18)F-FDG also may accumulate in benign processes. Knowledge of these (18)F-FDG-avid nonmalignant lesions is essential for accurate PET interpretation in oncologic patients to avoid a false-positive interpretation. Through the systematic review of the reports of PET/computed tomography (CT) studies performed in oncologic patients during a 6-month period, we found benign nonphysiological uptake of (18)F-FDG in more than 25% of studies. In half of these, (18)F-FDG uptake was moderate or marked in intensity, similar to that of malignant sites. A total of 73% of benign lesions were inflammatory in nature, with post-traumatic bone and soft-tissue abnormalities (including iatrogenic injury) and benign tumors accounting for the remainder. The differentiation of benign from malignant uptake of (18)F-FDG on PET alone may be particularly challenging as a result of the low anatomical resolution of PET and paucity of anatomical landmarks. Fusion imaging, namely PET/CT, has been shown to improve not only the sensitivity of PET interpretation but also its specificity. Aside from better anatomical localization of lesions on PET/CT, morphological characterization of lesions on CT often may improve the diagnostic accuracy of nonspecific (18)F-FDG uptake. Correlation with CT on fused PET/CT data may obviate the need for further evaluation or biopsy in more than one-third of scintigraphic equivocal lesions. Familiarity with (18)F-FDG-avid nonmalignant lesions also may extend the use of (18)F-FDG-PET imaging beyond the field of oncology. We have tabulated our experience with benign entities associated with increased (18)F-FDG uptake on whole-body PET/CT from 12,000 whole-body (18)F-FDG-PET/CT studies performed during a 4-year period.     

18F-FDG PET显像在胰腺恶性病变鉴别诊断及转移灶探查中的应用价值

目的研究18F-FDGPET显像在胰腺恶性肿瘤诊断与鉴别诊断中的应用价值。方法 40例临床疑为胰腺恶性病变的患者均行18F-FDGPET显像,对显像结果进行目测法及SUV值半定量分析,并结合CT,MRI等影像学检查进行综合诊断,最后诊断根据手术病理或经4个月以上随访证实。结果如果以SUV为2.5作为鉴别诊断胰腺病灶良恶性的阈值,24例证实为胰腺癌患者中18F-FDGPET显像正确诊断22例,16例胰腺良性病变患者18F-FDGPET检出13例,其灵敏度、特异度及准确性分别为91.7%（22/24）,81.3%（13/16）及87.5%（35/40）;而结合CT,MRI等其他检查结果进行综合诊断,其诊断灵敏度、特异度及准确性分别为91.7%（22/24）、87.5%（14/16）及90%（36/40）。恶性病变的SUV平均值为4.6±2.6,良性病变的SUV平均值为2.3±1.5,良恶性病变间SUV平均值差异有统计学意义（P〈0.01）。在转移灶的检出中,18F-FDGPET显像发现了全部38处转移灶,并发现6处CT,MRI未能发现的远处转移病灶,排除了1例CT认为是胰周转移性淋巴结肿大的病例。结论 18F-FDGPET对鉴别诊断胰腺良恶性肿瘤的灵敏度、特异性较高,尤其在远处转移灶的探查中有较高应用价值。     

18F-FDOPA PET imaging of brain tumors: comparison study with 18F-FDG PET and evaluation of diagnostic accuracy.

We evaluated the amino acid and glucose metabolism of brain tumors by using PET with 3,4-dihydroxy-6-(18)F-fluoro-l-phenylalanine ((18)F-FDOPA) and (18)F-FDG. METHODS: Eighty-one patients undergoing evaluation for brain tumors were studied. Initially, 30 patients underwent PET with (18)F-FDOPA and (18)F-FDG within the same week. Tracer kinetics in normal brain and tumor tissues were estimated. PET uptake was quantified by use of standardized uptake values and the ratio of tumor uptake to normal hemispheric tissue uptake (T/N). In addition, PET uptake with (18)F-FDOPA was quantified by use of ratios of tumor uptake to striatum uptake (T/S) and of tumor uptake to white matter uptake. The accuracies of (18)F-FDOPA and (18)F-FDG PET were determined by comparing imaging data with histologic findings and findings of clinical follow-up of up to 31 mo (mean, 20 mo). To further validate the accuracy of (18)F-FDOPA PET, (18)F-FDOPA PET was performed with an additional 51 patients undergoing brain tumor evaluation. RESULTS: Tracer uptake in tumors on (18)F-FDOPA scans was rapid, peaking at approximately 15 min after intravenous injection. Tumor uptake could be distinguished from that of the striatum by the difference in peak times. Both high-grade and low-grade tumors were well visualized with (18)F-FDOPA. The sensitivity for identifying tumors was substantially higher with (18)F-FDOPA PET than with (18)F-FDG PET at comparable specificities, as determined by simple visual inspection, especially for the assessment of low-grade tumors. Using receiver-operating-characteristic curve analysis, we found the optimal threshold for (18)F-FDOPA to be a T/S of greater than 1.0 (sensitivity, 96%; specificity, 100%) or a T/N of greater than 1.3 (sensitivity, 96%; specificity, 86%). The high diagnostic accuracy of (18)F-FDOPA PET at these thresholds was confirmed with the additional 51 patients (a total of 81 patients: sensitivity, 98%; specificity, 86%; positive predictive value, 95%; negative predictive value, 95%). No significant difference in tumor uptake on (18)F-FDOPA scans was seen between low-grade and high-grade tumors (P = 0.40) or between contrast-enhancing and nonenhancing tumors (P = 0.97). Radiation necrosis was generally distinguishable from tumors on (18)F-FDOPA scans (P < 0.00001). CONCLUSION: (18)F-FDOPA PET was more accurate than (18)F-FDG PET for imaging of low-grade tumors and evaluating recurrent tumors. (18)F-FDOPA PET may prove especially useful for imaging of recurrent low-grade tumors and for distinguishing tumor recurrence from radiation necrosis.     

11C-acetate PET imaging in hepatocellular carcinoma and other liver masses.

It is well known that (18)F-FDG PET has a high average false-negative rate of 40%-50% in the detection of hepatocellular carcinoma (HCC). This is not an acceptable accuracy, particularly in countries where this tumor is prevalent. In this study, we evaluated prospectively the characteristics of (11)C-acetate and (18)F-FDG metabolism in HCC and other liver masses. METHODS: Fifty-seven patients were recruited into this study, with masses consisting of 39 HCC; 3 cholangiocarcinomas; 10 hepatic metastases from lung, breast, colon, and carcinoid primary malignancies; and 5 benign pathologies, including focal nodular hyperplasia (FNH), adenoma, and hemangioma. All patients, except 2 with typical findings of hemangioma and 3 clinically obvious metastases, were confirmed histopathologically by liver biopsy or resection. All patients fasted for at least 6 h and blood glucose concentration was measured before they underwent dual PET radiopharmaceutical evaluation of the upper abdomen with (11)C-acetate and (18)F-FDG. RESULTS: In the subgroup of HCC patients with the number of lesions < or = 3 (32 patients; 55 lesions; mean size +/- SD, 3.5 +/- 1.9 cm), the sensitivity of detection by (11)C-acetate is 87.3% ((11)C-acetate maximum SUV [SUV(max)] = 7.32 +/- 2.02, with a lesion-to-normal liver ratio of 1.96 +/- 0.63), whereas the sensitivity of detection by (18)F-FDG is only 47.3%, and 34% lesions show uptake of both tracers. None of the lesions was negative for both tracers (100% sensitivity using both tracers). In some lesions and in the subgroup of HCC patients (n = 7) with multifocal or diffuse disease, dual-tracer uptake by different parts of the tumor is demonstrated. Histopathologic correlation suggests that the well-differentiated HCC tumors are detected by (11)C-acetate and the poorly differentiated types are detected by (18)F-FDG. All 16 non-HCC malignant (cholangiocarcinoma and metastatic) liver lesions do not show abnormal (11)C-acetate metabolism. Of the benign liver lesions, only FNH shows mildly increased (11)C-acetate activities ((11)C-acetate SUV(max) = 3.59, with a lesion-to-normal liver ratio of 1.25). CONCLUSION: (11)C-Acetate has a high sensitivity and specificity as a radiotracer complementary to (18)F-FDG in PET imaging of HCC and evaluation of other liver masses.     

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.     

The role of gastric distention in differentiating recurrent tumor from physiologic uptake in the remnant stomach on 18F-FDG PET.

Physiologic (18)F-FDG uptake in the stomach can often cause false-positive results and lowers the usefulness of (18)F-FDG PET in evaluating the remnant stomach. We assessed the role of gastric distension to see whether it is beneficial for the differentiation of recurrent tumors from physiologic (18)F-FDG uptake in the remnant stomach. METHODS: Thirty patients (22 men and 8 women; age range, 27-80 y; mean age, 58.3 y) with a history of subtotal gastrectomy for gastric cancer underwent (18)F-FDG PET for various clinical indications. After whole-body imaging, the patients were asked to drink water, and then spot imaging of the stomach was performed. (18)F-FDG uptake in the remnant stomach was considered positive for malignancy if it was persistently increased, whether focal or diffuse, after water ingestion. We used 2 standardized uptake value (SUV) criteria to differentiate benign from malignant uptake. First, a lesion was considered benign if its SUV was less than 2 on whole-body imaging. Second, for a lesion with an SUV of 2 or above, it was classified as benign if SUV decreased by more than 10% after water ingestion. RESULTS: Visual analysis of whole-body images produced 9 true-negative, 4 false-positive, 16 true-positive, and 1 false-negative results. Use of additional spot images produced 12 true-negative, 1 false-positive, 15 true-positive, and 2 false-negative results. When an SUV cutoff of 2 was applied for malignancy before water ingestion, all 17 patients with local recurrence were correctly identified, but 11 of the 13 patients without local recurrence were falsely considered to have a recurrent tumor in the remnant stomach. To reduce the false-positive results, we used the second SUV criterion after water ingestion. Use of that criterion produced 4 false-negative results although it correctly identified the 11 false-positive results as true negative. CONCLUSION: Gastric distension by having patients drink a glass of water seems to be a simple, cost-effective way of improving the diagnostic accuracy of (18)F-FDG PET in patients with suspected recurrence in the remnant stomach. Visual analysis with special attention to the configuration of (18)F-FDG activity after water ingestion seems to be more useful than the change in SUV in evaluating the remnant stomach.     

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。