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.     

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%.     

Early tumor response to Hsp90 therapy using HER2 PET: comparison with 18F-FDG PET.

We compared (68)Ga-DOTA-F(ab')(2)-herceptin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid [HER2 PET]) and (18)F-FDG PET for imaging of tumor response to the heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17AAG). METHODS: Mice bearing BT474 breast tumor xenografts were scanned with (18)F-FDG PET and HER2 PET before and after 17AAG treatment and then biweekly for up to 3 wk. RESULTS: Within 24 h after treatment, a significant decrease in HER2 was measured by HER2 PET, whereas (18)F-FDG PET uptake, a measure of glycolysis, was unchanged. Marked growth inhibition occurred in treated tumors but became evident only by 11 d after treatment. Thus, Her2 downregulation occurs independently of changes in glycolysis after 17AAG therapy, and Her2 reduction more accurately predicts subsequent tumor growth inhibition. CONCLUSION: HER2 PET is an earlier predictor of tumor response to 17AAG therapy than (18)F-FDG PET.     

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.     

Aortic wall inflammation due to Takayasu arteritis imaged with 18F-FDG PET coregistered with enhanced CT.

The purpose of this study was to evaluate the ability of (18)F-FDG PET to identify aortitis and to localize and follow disease activity in patients with Takayasu arteritis. The value of using (18)F-FDG PET coregistered with enhanced CT in determining vascular lesion sites and inflammatory activity was assessed. METHODS: Takayasu arteritis was diagnosed according to the predefined criteria. Eleven patients with Takayasu arteritis in the active stage, 3 patients with Takayasu arteritis in the inactive stage, and 6 healthy subjects underwent (18)F-FDG PET coregistered with enhanced CT and the inflammatory vascular lesion was evaluated by using the standardized uptake value (SUV) of (18)F-FDG accumulation as an index. Two patients with active disease were analyzed by sequential (18)F-FDG PET scans during treatment. RESULTS: The (18)F-FDG PET revealed intense (18)F-FDG accumulation (SUV > or = 2.7) in the vasculature of 2 of the 11 cases in the active stage of Takayasu arteritis. The other 9 patients in the active stage revealed weak (18)F-FDG accumulation (2.3 > or = SUV > or = 1.2). No significant (18)F-FDG accumulation was observed in the patients with inactive disease (SUV < or = 1.2) and 6 control healthy subjects (SUV < 1.3). Given the cutoff SUV is 1.3, the sensitivity of (18)F-FDG PET analysis of Takayasu arteritis is 90.9% and the specificity is 88.8%. (18)F-FDG PET coregistered with enhanced CT localized (18)F-FDG accumulation in the aortic wall in the patients with Takayasu arteritis who had weak (18)F-FDG accumulation that could not otherwise be identified anatomically. Finally, (18)F-FDG accumulation resolved with therapy in 2 active cases. The disappearance of (18)F-FDG accumulation did not coincide with the level of general inflammatory markers. CONCLUSION: The (18)F-FDG PET images coregistered with enhanced CT images showed the distribution and inflammatory activity in the aorta, its branches, and the pulmonary artery in patients with active Takayasu arteritis, even those who had weak (18)F-FDG accumulation. The intensity of accumulation decreased in response to therapy.     

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.     

Solid splenic masses: evaluation with 18F-FDG PET/CT.

Our objective was to assess the role of (18)F-FDG PET/CT in the evaluation of solid splenic masses in patients with a known malignancy and in incidentally found lesions in patients without known malignancy. METHODS: Two groups of patients were assessed: (a) 68 patients with known malignancy and a focal lesion on PET or a solid mass on CT portions of the PET/CT study; and (b) 20 patients with solid splenic masses on conventional imaging without known malignancy. The standard of reference was histology (n = 16) or imaging and clinical follow-up (n = 72). The lesion size, the presence of a single versus multiple splenic lesions, and the intensity of (18)F-FDG uptake expressed as a standardized uptake value (SUV) were recorded. The ratio of the SUV in the splenic lesion to the background normal splenic uptake was also calculated. These parameters were compared between benign and malignant lesions within each of the 2 groups of patients and between the 2 groups. RESULTS: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of (18)F-FDG PET/CT in differentiating benign from malignant solid splenic lesions in patients with and without malignant disease were 100%, 100%, 100%, and 100% versus 100%, 83%, 80%, and 100%, respectively. In patients with known malignant disease, an SUV threshold of 2.3 correctly differentiated benign from malignant lesions with the sensitivity, specificity, PPV, and NPV of 100%, 100%, 100%, and 100%, respectively. In patients without known malignant disease, false-positive results were due to granulomatous diseases (n = 2). CONCLUSION: (18)F-FDG PET can reliably discriminate between benign and malignant solid splenic masses in patients with known (18)F-FDG-avid malignancy. It also appears to have a high NPV in patients with solid splenic masses, without known malignant disease. (18)F-FDG-avid splenic masses in patients without a known malignancy should be further evaluated as, in our series, 80% of them were malignant.     

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.     

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.     

Tumor localization of 16beta-18F-fluoro-5alpha-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer.

This trial was an initial assessment of the feasibility, in vivo targeting, and biokinetics of 16beta-(18)F-fluoro-5alpha-dihydrotestosterone ((18)F-FDHT) PET in patients with metastatic prostate cancer to assess androgen receptor expression. METHODS: Seven patients with progressive clinically metastatic prostate cancer underwent (18)F-FDG and (18)F-FDHT PET scans in addition to conventional imaging methods. Three patients had their studies repeated 1 mo later, 2 while on testosterone therapy, and the third after treatment with 17-allylamino-17-demethoxygeldanamycin (17-AAG). High-pressure liquid radiochromatography was used to separate (18)F-FDHT from radiolabeled metabolites. Lesion-by-lesion comparisons between the (18)F-FDHT, (18)F-FDG, and conventional imaging methods were performed. RESULTS: Metabolism of (18)F-FDHT was rapid, with 80% conversion within 10 min to radiolabeled metabolites that circulated bound to plasma proteins. Tumor uptake was rapid and tumor retention was prolonged. Fifty-nine lesions were identified by conventional imaging methods. (18)F-FDG PET was positive in 57 of 59 lesions (97%), with an average lesion maximum standardized uptake value (SUV(max)) = 5.22. (18)F-FDHT PET was positive in 46 of 59 lesions (78%), with the average positive lesion SUV(max) = 5.28. Treatment with testosterone resulted in diminished (18)F-FDHT uptake at the tumor site. CONCLUSION: (18)F-FDHT localizes to tumor sites in patients with progressive clinically metastatic prostate cancer and may be a promising agent to analyze antigen receptors and their impact on the clinical management of prostate cancer.     

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.     

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.     

18F-FDG PET of gliomas at delayed intervals: improved distinction between tumor and normal gray matter.

We hypothesized that delineation of gliomas from gray matter with 18F-FDG PET could be improved by extending the interval between 18F-FDG administration and PET data acquisition. The purposes of this study were, first, to analyze standard and delayed 18F-FDG PET images visually and quantitatively to determine whether definition of tumor improved at later imaging times and, second, to investigate the dynamics of model-derived kinetic rate constants, particularly k4. METHODS: Nineteen adult patients with supratentorial gliomas were imaged from 0 to 90 min and once or twice later at 180-480 min after injection. In 15 patients, arterial sampling provided the early input function. Venous sampling provided the remaining curve to the end of the imaging sequence. Standardized uptake value (SUV) was calculated as tissue concentration of tracer per injected tracer dose per body weight. Ratios of tumor SUV relative to the SUV of gray matter, brain (including gray and white matter), or white matter were calculated at each imaging time point. Dynamic image data from tumor, gray matter, brain, or white matter were analyzed using a 2-compartment, 4-parameter model applied for the entire duration of imaging, in which delay, K1, distribution volume, k3, and k4 were optimized using a nonlinear optimization method. Parameter estimation for each region included both an early subset of data from a conventional dynamic imaging period (0-60 min) and the full, extended dataset for each region. RESULTS: In 12 of the 19 patients, visual analysis showed that the delayed images better distinguished the high uptake in tumors relative to uptake in gray matter. SUV comparisons also showed greater uptake in the tumors than in gray matter, brain, or white matter at the delayed times. The estimated k4 values for tumors were not significantly different from those for gray matter in early imaging analysis but were lower (P < 0.01) using the extended-time data. CONCLUSION: The kinetic parameter results confirm the visual and SUV interpretation that tumor enhancement is greater than enhancement of surrounding brain regions at later imaging times, consistent with a greater effect of FDG-6-phosphate degradation on normal brain relative to glioma.     

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.     

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.     

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.     

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.     

Evaluation of 18F-FDG PET with bladder irrigation in patients with uterine and ovarian tumors.

The purpose of this study was to evaluate PET using (18)F-FDG for gynecologic lesions with continuous bladder irrigation to eliminate artifacts from the (18)F-FDG activity in the bladder. METHODS: Forty-one patients were studied. They had 23 cervical uterine lesions (15 cases of cancer, 5 recurrences, 3 nonrecurrences); 8 cases of uterine corpus cancer, including 2 recurrences; and 10 ovarian masses (6 malignant, 4 nonmalignant). All cases of cancer were histologically proven; however, 2 cases of nonrecurrent uterine cervical carcinomas were diagnosed by clinical course. Continuous bladder irrigation was performed 35-55 min after intravenous administration of 185-370 MBq (18)F-FDG, and an emission scan was obtained 40-55 min after intravenous administration. Standardized uptake value (SUV) was used to estimate the degree of (18)F-FDG uptake quantitatively. RESULTS: After bladder irrigation, the (18)F-FDG activity in the urinary tract was eliminated in 33 patients, so that detection of tumor (18)F-FDG accumulation was easy. Two patients showed residual activity in the urinary bladder, and 6 patients showed activity in the ureter. An artifact was seen in 1 patient with residual activity in the urinary bladder caused by insufficient irrigation. However, these residual activities had no influence on detecting (18)F-FDG accumulation in tumor. The mean (+/-SD) of SUVs of malignant lesions was 6.04 +/- 3.22, that of nonmalignant lesions was 1.71 +/- 1.12, and the difference was significant (P = 0.0002). SUVs of all malignant lesions were greater than 2.0, and SUVs of all nonmalignant lesions, except the 1 case of ovarian fibroma, were less than 2.0. CONCLUSION: (18)F-FDG PET with continuous bladder irrigation is useful for eliminating (18)F-FDG activity in the bladder and for differentiating between malignant and nonmalignant uterine or ovarian masses.     

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.     

Deep-inspiration breath-hold PET/CT: clinical findings with a new technique for detection and characterization of thoracic lesions.

Respiratory motion during PET/CT acquisition can cause misregistration and inaccuracies in calculation of standardized uptake values (SUVs). Our aim was to compare the detection and characterization of thoracic lesions on PET/CT with and without a deep-inspiration protocol. METHODS: We studied 15 patients with suspected pulmonary lesions who underwent clinical PET/CT, followed by deep-inspiration breath-hold (BH) PET/CT. In BH CT, the whole chest of the patient was scanned in 15 s at the end of deep inspiration. For BH PET, patients were asked to hold their breath 9 times for 20-s intervals. One radiologist reviewed images, aiming to detect and characterize pulmonary, nodal, and skeletal abnormalities. Clinical CT and BH CT were compared for number, size, and location of lesions. Lesion SUVs were compared between clinical PET and BH PET. Images were also visually assessed for accuracy of fusion and registration. RESULTS: All patients had lesions on clinical CT and BH CT. Pulmonary BH CT detected more lesions than clinical CT in 13 of 15 patients (86.7%). The total number of lung lesions detected increased from 53 with clinical CT to 82 with BH CT (P<0.001). Eleven patients showed a total of 31 lesions with abnormal (18)F-FDG uptake. BH PET/CT had the advantage of reducing misregistration and permitted a better localization of sites with (18)F-FDG uptake. A higher SUV was noted in 22 of 31 lesions on BH PET compared with clinical PET, with an average increase in SUV of 14%. CONCLUSION: BH PET/CT enabled an increased detection and better characterization of thoracic lesions compared with a standard PET/CT protocol, in addition to more precise localization and quantification of the findings. The technique is easy to implement in clinical practice and requires only a minor increase in the examination time.