Comparison of [18F]fluorodeoxyglucose uptake with glucose transporter-1 expression and proliferation rate in human glioma and non-small-cell lung cancer

To clarify the biological significance of [18F]fluorodeoxyglucose (18F-FDG) accumulation in patients with cancer, we assessed the relationships between 18F-FDG uptake and glucose transporter-1 (GLUT-1) expression and proliferation rate in human glioma and lung cancer. We obtained FDG PET images and measured standardized uptake values (SUVs) of primary tumours in 13 patients with brain glioma and 25 patients with non-small-cell lung cancer. After surgery, portions of respected tumours were obtained, and the proliferation rate was measured as proliferation index (per cent of (S+G2+M)/(G0+G1+S+G2+M)) using DNA flow cytometry. The expression of GLUT-1 in a tumour was evaluated by using immunostaining. We classified GLUT-1 expression as grade 0 (no positive cell), grade 1 (< 10% cells positive), grade 2 (11-50% cells positive) and grade 3 (51-100% cells positive). Based on the expression of GLUT-1, cases with grades 0, 1, 2 and 3 showed SUVs of 6.1 +/- 2.8, 5.0 +/- 3.2, 8.3 +/- 3.3 and 10.4 +/- 6.6, respectively (P < 0.05). Non-small-cell lung cancer showed higher FDG uptake (SUV, 8.5 +/- 5.1) and higher GLUT-1 expression (grade, 2.0 +/- 1.0) than did brain glioma (SUV, 4.7 +/- 2.5; grade, 0.8 +/- 0.8). Based on the total number of cases, SUVs did not relate to proliferation index (r = 0.19). In non-small-cell lung cancer, SUVs did not correlate with proliferation index, whereas in glioma, SUVs were strongly related to proliferation index (r = 0.79, P < 0.01). In conclusion, FDG uptake generally correlated with GLUT-1 expression in non-small-cell lung cancer and glioma. In the case of glioma, FDG uptake also indicated increased cellular proliferation, which was not demonstrated in non-small-cell lung cancer.     

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.     

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.     

Usefulness of fasting 18F-FDG PET in identification of cardiac sarcoidosis.

Cardiac PET using (18)F-FDG under fasting conditions (fasting (18)F-FDG PET) is a promising technique for identification of cardiac sarcoidosis and assessment of disease activity. The aim of this study was to investigate the usefulness of fasting (18)F-FDG PET in detecting inflammatory lesions of cardiac sarcoidosis from a pathophysiologic standpoint. METHODS: Twenty-two patients with systemic sarcoidosis were classified into 2 groups of 11 each according to the presence or absence of sarcoid heart disease. Cardiac sarcoidosis was diagnosed according to the Japanese Ministry of Health and Welfare guidelines for diagnosing cardiac sarcoidosis with the exception of scintigraphic criteria. Nuclear cardiac imaging with fasting (18)F-FDG PET, (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) SPECT, and (67)Ga scintigraphy were performed in all patients. PET and SPECT images were divided into 13 myocardial segments and the standardized uptake value (SUV) of (18)F-FDG was calculated and defect scores (DS) for (99m)Tc-MIBI uptake were assessed for each segment. The total SUV (T-SUV) and total DS (TDS) were calculated as the sum of measurements for all 13 segments, and the diagnostic accuracy of fasting (18)F-FDG PET was compared with that of the other nuclear imaging modalities. In addition, pathophysiologic relationships between inflammatory activity and myocardial damage were examined by segmental comparative study using the SUV and DS. RESULTS: In patients with cardiac sarcoidosis, fasting (18)F-FDG PET revealed a higher frequency of abnormal myocardial segments than (99m)Tc-MIBI SPECT (mean number of abnormal segments per patient: 6.6 +/- 3.0 vs. 3.0 +/- 3.2 [mean +/- SD], P < 0.05). The sensitivity of fasting (18)F-FDG PET in detecting cardiac sarcoidosis was 100%, significantly higher than that of (99m)Tc-MIBI SPECT (63.6%) or (67)Ga scintigraphy (36.3%). The accuracy of fasting (18)F-FDG PET was significantly higher than (67)Ga scintigraphy. The T-SUV demonstrated a good linear correlation with serum angiotensin-converting enzyme levels (r = 0.83, P < 0.01), and the TDS showed a significant negative correlation with the left ventricular ejection fraction (r = -0.82, P < 0.01). In abnormal myocardial segments on the nuclear scan, the SUV showed a significant negative correlation with the DS (r = -0.63, P < 0.0001). CONCLUSION: This study suggests that fasting (18)F-FDG PET can detect the early stage of cardiac sarcoidosis, in which fewer perfusion abnormalities and high inflammatory activity are noted, before advanced myocardial impairment.     

Delayed (18)F-FDG PET for detection of paraaortic lymph node metastases in cervical cancer patients.

This prospective study investigated the usefulness of dual-phase (18)F-FDG PET scans (40 min and 3 h) in detecting paraaortic lymph node (PALN) metastasis for cervical cancer. METHODS: One hundred four consecutive cervical cancer patients (International Federation of Gynecology and Obstetrics staging Ib-IVb, recurrent or persistent tumors) were included. All patients received a whole-body (18)F-FDG PET scan at 40 min and an additional scan from the T11 level to the inguinal region at 3 h after injection of 370 MBq (18)F-FDG. The maximum standardized uptake value (SUV) and retention index (RI [%], obtained by subtracting the normalized SUV value obtained at 40 min from that at 3 h) of the lesions were determined. RESULTS: In all, 38 of the 104 patients were confirmed to have PALN metastases. For 31 patients (81.6%) with 13 upper (L1-L2 level) and 30 lower (L3-L4 level) PALNs, these metastases were detected with the 40-min scan. In addition, for 7 patients (18.4%) with 7 lower PALNs, metastases were found with the 3-h scan (RI = 12.6%). Two patients (3.0%) had 2 false-positive lesions initially (40 min) but were classified as benign with the 3-h scan. The sensitivity, specificity, and accuracy of (18)F-FDG PET scans at 40 min were 81.6%, 97.0%, and 91.3%, respectively. These quantities were all 100% when both the 40-min and 3-h scans were taken together. Eight patients (21.1%) had their treatment planning changed. We divided the 38 patients into 2 subgroups. Subgroup A included those with either only upper or only lower PALN metastases, and subgroup B included those with both upper and lower PALN metastases. In subgroup A, the SUV values were greater in the upper than in the lower PALNs in both the 40-min and 3-h images (P = 0.077). In subgroup B, there was no significant difference of SUV values between upper and lower PALNs in the 40-min (P = 0.433) and 3-h (P = 0.937) images. CONCLUSION: Our results showed that an additional 3-h scan is helpful for PALN detection of cervical cancer patients. A delayed image (3 h) is especially useful for lower PALN metastases.     

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.     

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.     

Optimizing delayed scan time for FDG PET: comparison of the early and late delayed scan

OBJECTIVES: Although dual-time-point scans have been widely used to improve the diagnostic efficacy of FDG PET in differentiating between malignant and benign lesions, no optimized delayed scan time-point has yet been recommended in clinical practice. Our study aimed to explore the most appropriate time for a delayed scan by comparing early and late delayed scans. METHODS: Eighty patients with suspected malignancy were given a three-phase (64 min, 110 min, 233 min after FDG injection) PET/CT scan. The maximum standardized uptake values (SUVs) in the three-phase scans were recorded as SUV1, SUV2 and SUV3, respectively, and compared among three-phase imaging. Retention indices (RIs) of each lesion in two delayed phases were calculated according to the formulae: RI1=SUV2-SUV1/SUV1 x100% and RI2=SUV3-SUV1/SUV1 x100%. RI1 and RI2 in both malignant and benign groups were assessed through correlation analysis. The diagnostic values of two delayed scans were compared through the analysis of the receiver operating characteristic curves. RESULTS: One hundred and nine of 148 lesions were malignant, and 39/148 lesions benign, which were verified by pathological, clinical, laboratory or radiological examination. RI1 and RI2 in malignancy were 14.8+/-13.1% and 10.8+/-20.5% respectively, and the correlation coefficient was 0.6 (P=0.0001). RI1 and RI2 in benign lesions were 11.3+/-28.2% and 9.3+/-42.4%, respectively, and the correlation coefficient was 0.6 (P=0.0001). The area under the ROC curve for RI1 was 0.627+/-0.050 (null hypothesis: true area=0.5, P=0.0130); whereas the area under the ROC curve for RI2 was 0.563+/-0.052 (null hypothesis: true area=0.5, P=0.2321), suggesting that the late delayed scan may have no diagnostic value. CONCLUSION: The retention index values in the two delayed phases have good relativity. The diagnostic value of early delayed imaging is higher than that of late delayed imaging. An early delayed scan, according to our research, should be recommended in clinical practice.     

18F-FDG uptake in squamous cell carcinoma of the cervix is correlated with glucose transporter 1 expression.

This prospective study investigates the relationship between glucose transporter-1 (Glut-1) expression and PET images using (18)F-FDG and its uptake and compares them with the tumor status (primary vs. recurrent or persistent), initial grade of histologic differentiation, and International Federation of Gynecologic Obstetrics (FIGO) staging for cervical cancer patients. METHODS: A dual-phase (18)F-FDG PET scan was performed on 51 participants within the 2 wk before surgery or biopsy. (18)F-FDG uptake was quantified by calculating standardized uptake values (SUVs). After (18)F-FDG PET scanning, 51 histologically proven squamous cell carcinoma specimens were examined to determine their degree of differentiation, using hematoxylin and eosin staining, and the expression of Glut-1 by an immunohistochemical stain. Twenty normal cervical and 20 cervical intraepithelial neoplasia (CIN) sets of tissue were also used to compare the results of Glut-1 expression in these tissues. The expression of Glut-1 was the product of (the intensity [with grades 0-3, defined qualitatively]) with (percentages of the lesion area that were positive). The results of Glut-1 expression were analyzed in combination with the SUVs (SUV1 was that at 40 min and SUV2 was that at 3 h), tumor status, initial cell differentiation, and FIGO staging. RESULTS: Significant overexpression of Glut-1 was noted in 48 of the 51 (94.1%) cancer specimens. None or only minimal expression of Glut-1 was observed in basal layers of normal and CIN tissues. Significant positive correlation was observed between Glut-1 expression and the SUVs in cervical cancer specimens (r = 0.74, P < 0.000 for SUV1 and r = 0.65, P < 0.000 for SUV2). In recurrent or persistent tumor, tumor size was significantly associated with both Glut-1 expression (r = 0.508, P = 0.011) and SUV1 (r = 0. 456, P = 0.025). For recurrent or persistent tumor, only SUV1 reached statistical significance when compared with lymph node metastasis (P = 0.0226). CONCLUSION: Glut-1 expression was related to (18)F-FDG uptake in cervical cancer patients. Recurrent or persistent cervical cancer tumor had significantly higher Glut-1 expression than metastatic lymph nodes. The values of SUV and the expression of Glut-1 did not correlate with the initial grade of histologic differentiation and FIGO staging.     

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

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

The Clinical Role of Dual-Time-Point 18F-FDG PET/CT in Differential Diagnosis of the Thyroid Incidentaloma

Thyroid incidentalomas are common findings during imaging studies including ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) for cancer evaluation. Although the overall incidence of incidental thyroid uptake detected on PET imaging is low, clinical attention should be warranted owing to the high incidence of harboring primary thyroid malignancy. We retrospectively reviewed 2,368 dual-time-point ¹⁸F-FDG PET/CT cases that were undertaken for cancer evaluation from November 2007 to February 2009, to determine the clinical impact of dual-time-point imaging in the differential diagnosis of thyroid incidentalomas. Focal thyroid uptake was identified in 64 PET cases and final diagnosis was clarified with cytology/histology in a total of 27 patients with ¹⁸F-FDG-avid incidental thyroid lesion. The maximum standardized uptake value (SUVmax) of the initial image (SUV1) and SUVmax of the delayed image (SUV2) were determined, and the retention index (RI) was calculated by dividing the difference between SUV2 and SUV1 by SUV1 (i.e., RI = [SUV2 - SUV1]/SUV1 × 100). These indices were compared between patient groups that were proven to have pathologically benign or malignant thyroid lesions. There was no statistically significant difference in SUV1 between benign and malignant lesions. SUV2 and RI of the malignant lesions were significantly higher than the benign lesions. The areas under the ROC curves showed that SUV2 and RI have the ability to discriminate between benign and malignant thyroid lesions. The predictability of dual-time-point PET parameters for thyroid malignancy was assessed by ROC curve analyses. When SUV2 of 3.9 was used as cut-off threshold, malignancy on the pathology could be predicted with a sensitivity of 87.5 % and specificity of 75 %. A thyroid lesion that shows RI greater than 12.5 % could be expected to be malignant (sensitivity 88.9 %, specificity 66.3 %). All malignant lesions showed an increase in SUVmax on the delayed images compared with the initial images. But in the group of benign lesions, 37.5 % (6/16) showed a decrease or no change in SUVmax. Dual-time-point ¹⁸F-FDG PET/CT, obtaining additional images 2 h after injection, seems to be a complementary method for the differentiation between malignancy and benignity of incidental thyroid lesions.     

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.     

Dual time-point FDG PET/CT and FDG uptake and related enzymes in lymphadenopathies: preliminary results

Purpose

The purpose of this study was to determine the ability of dual time-point (DTP) PET/CT with ¹⁸F-FDG to discriminate between malignant and benign lymphadenopathies. The relationship between DTP FDG uptake and glucose metabolism/hypoxia markers in lymphadenopathies was also assessed.

Methods

Patients with suspected lymphoma or recently diagnosed treatment-naive lymphoma were prospectively enrolled for DTP FDG PET/CT (scans 60 min and 180 min after FDG administration). FDG-avid nodal lesions were segmented to yield volume and standardized uptake values (SUV), including SUVmax, SUVmean, cSUVmean (with partial volume correction), total lesion glycolysis (TLG) and cTLG (with partial volume correction). Expression of glucose transporter-1 (GLUT-1), hexokinase-II (HK-II), glucose-6-phosphatase (G6Pase) and hypoxia-inducible factor-1alpha (HIF-1alpha) were assessed with immunohistochemistry and enzyme activity was determined for HK and G6Pase.

Results

FDG uptake was assessed in 203 lesions (146 malignant and 57 benign). Besides volume, there were significant increases over time for all parameters, with generally higher levels in the malignant lesions. The retention index (RI) was not able to discriminate between malignant and benign lesions. Volume, SUVmax, TLG and cTLG for both scans were able to discriminate between the two groups statistically, but without complete separation. Glucose metabolism/hypoxia markers were assessed in 15 lesions. TLG and cTLG were correlated with GLUT-1 expression on the 60-min scan. RI-max and RI-mean and SUVmax, SUVmean and cSUVmean on the 60-min scan were significantly correlated with HK-II expression.

Conclusion

RI was not able to discriminate between malignant and benign lesions, but some of the SUVs were able to discriminate on the 60-min and 180-min scans. Furthermore, FDG uptake was correlated with GLUT-1 and HK-II expression.

     

Hexokinase-II expression in untreated oral squamous cell carcinoma: Comparison with FDG PET imaging

Hexokinase is thought to be one of the key factors of glucose catabolism in the cell. The aim of this study was to investigate the relationship between HK-II expression and 18F-fluoro-2-deoxy-D-glucose (FDG) uptake in human untreated oral squamous cell carcinoma (OSCC). Pre-operatively FDG positron emission tomography (PET) was performed 60 min after FDG injection in all the patients. Maximum standardized uptake value (SUV) was used for evaluation of tumor FDG uptake. Tumor sections were stained immunohistochemically for HK-II. All the tumor sections stained positive for HK-II. Eighteen (95%) tumors in HK-II showed immunostained positive area >50%. HK-II findings revealed eleven (58%) tumors with strong intensity, six (32%) with moderate intensity and two with weak intensity (10%). There was no statistically significant correlation between SUV and the expression of HK-II (p = 0.46). In conclusion, OSCC showed increased FDG accumulation and overexpression of HK-II. However, we did not find any significant relationship between high FDG uptake and overexpression of HK-II in this patient population, and thus other properties need to be evaluated in order to elucidate key factors responsible for FDG activity in OSCC.     

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

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

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.     

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

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

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.     

18F-FDG PET/CT联合肺动脉灌注成像指数在单发肺结节中的应用价值

目的探讨18F-FDG PET/CT联合320容积CT双入口灌注成像(DI-CTP)肺动脉灌注指数(PPI)对单发性肺结节的鉴别诊断价值。方法搜集经病理证实40例单发性肺结节患者的18F-FDG PET/CT及320排CT灌注成像影像资料(恶性结节24例、良性结节16例),PET/CT以结节18F-FDG摄取值SUV≥2.5为诊断恶性结节阈值,18F-FDG PET/CT联合PPI则在SUV≥2.5诊断阈值的基础上综合PPI<50%判定,并分析SUV与PP均值在良恶性结节间差异性及相关性。结果PET/CT联合PPI正确诊断38例,其中恶性结节22例、良性结节16例,误诊2例。18F-FDG PET/CT联合PPI诊断肺单发结节的敏感性91.6%,特异性100%,准确性95.0%;18F-PDG摄取值SUV在良、恶性结间差异无统计学意义(t=1.66,P>0.05),而PPI均值在良、恶性结节间差异有统计学意义(t=-3.14,P<0.01);SUV与PPI间相关性无统计学意义(r=0.20,P>0.05)。结论18F-FDG PET/CT联合PPI可以提高诊断肺单发肺结节敏感性、特异性和准确性,减少误诊率。     

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.