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

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

Dual time point 2-[18F]fluoro-2'-deoxyglucose positron emission tomography in chronic bacterial osteomyelitis

OBJECTIVE: Quantitative dual time point imaging with [F]fluorodeoxyglucose positron emission tomography (F-FDG PET) has recently been found to be more accurate than single time point scanning in the discrimination between benign lesions and malignancy in various conditions. In our study we investigated glucose metabolism in chronic bacterial osteomyelitis (COM) by using F-FDG PET and a dual time protocol. METHODS: Seventeen non-diabetic patients with histopathologically proven COM and four non-diabetic patients with malignant bone disease were prospectively investigated with dual time F-FDG PET. All lesions were detected by their increased F-FDG uptake 30 and 90 min after injection of 370 MBq of F-FDG. The maximum and mean lesional standardized uptake values (SUV(max) and SUV(mean) after 30 and 90 min were determined. RESULTS: The median SUV(max) and SUV(mean) values of all osteomyelitic lesions at 30 min were 1.85 (range, 0.45-3.45) and 1.1 (range, 0.21-1.99), respectively. The median SUV(max) and SUV(mean) values of all malignant lesions at 30 min were 3.19 (range, 2.31-4.7) and 2.82 (range, 2.4-3.71), respectively. At 90 min the median SUV(max) and SUV(mean) of all osteomyelitic lesions were 1.78 (range, 0.4-2.93) and 1.1 (range, 0.18-1.72), respectively. At the same time point the median SUV(max) and SUV(mean) of all malignant lesions were 4.1 (range, 3.52-5.32) and 3.34 (range, 2.81-4.12), respectively. In osteomyelitis the SUV(max) and SUV(mean) between 30 and 90 min post-injection remained stable or decreased in 16/17 patients. In these patients a median decrease of 6% for SUV(max) (range, 1-31%) and a median decrease of 8.5% for SUV(mean) (range, 0-24%) was observed. Changes of SUV(max) and SUV(mean) between 30 and 90 min were highly significant (P<0.05). In one patient SUV(max) and SUV(mean) increased over the time. The histology of this patient revealed multiple foreign body granulomas in addition to a mononuclear infiltrate. In malignant lesions the SUV(max) and SUV(mean) between 30 and 90 min post-injection increased. CONCLUSION: Our preliminary results indicate that dynamic dual time point F-FDG PET provides a characteristic pattern in chronic osteomyelitis similar to inflammatory processes in other locations. This pattern may be of value in the differentiation between COM and malignant bone lesions.     

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

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

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.     

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.     

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.     

Effects of pegfilgrastim on normal biodistribution of 18F-FDG: preclinical and clinical studies.

The purpose of this study was to evaluate the effects of pegfilgrastim, a long-acting granulocyte colony-stimulating factor, on the normal biodistribution of (18)F-FDG in an animal model and in humans. METHODS: Two groups of 12 rats received a single subcutaneous injection of either normal saline or pegfilgrastim. One, 7, 14, and 21 d after injection, biodistribution studies were performed 1 h after (18)F-FDG injection. Sixteen breast cancer patients underwent baseline (18)F-FDG PET/CT and, approximately 1 wk after receiving 1 dose of docetaxel and adjunctive pegfilgrastim, follow-up (18)F-FDG PET/CT (scan 2). Standardized uptake values corrected for lean body mass (SUL) were determined for several normal organs before and after therapy. RESULTS: In rats, bone marrow (18)F-FDG uptake (standardized uptake value) was higher in the pegfilgrastim group 1 d after injection (mean +/- SD, 8.3 +/- 4.1 vs. 2.5 +/- 0.2, P < 0.05), whereas (18)F-FDG uptake in blood was lower (0.41 +/- 0.06 vs. 0.49 +/- 0.01, P < 0.05). In patients, mean SUL was higher in bone marrow (4.49 +/- 1.50 vs. 1.33 +/- 0.22, P < 0.0001), spleen (3.29 +/- 0.83 vs. 1.23 +/- 0.23, P < 0.0001), and liver (1.45 +/- 0.25 vs. 1.31 +/- 0.23, P = 0.01) but lower in brain (4.18 +/- 0.76 vs. 5.14 +/- 1.44, P < 0.01) on scan 2 than on the baseline scan. CONCLUSION: In both the animal model and humans, pegfilgrastim markedly increased bone marrow uptake of (18)F-FDG and reduced (18)F-FDG uptake in some normal tissues. These profound alterations in (18)F-FDG biodistribution induced by pegfilgrastim must be considered when one is evaluating quantitative (18)F-FDG PET scans for tumor response to therapy.     

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.     

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.     

Clinical implications of different image reconstruction parameters for interpretation of whole-body PET studies in cancer patients.

The standardized uptake value (SUV) is the most commonly used parameter to quantify the intensity of radiotracer uptake in tumors. Previous studies suggested that measurements of (18)F-FDG accumulation in tissue might be affected by the image reconstruction method, but the clinical relevance of these findings has not been assessed. METHODS: Phantom studies were performed and clinical whole-body (18)F-FDG PET images of 85 cancer patients were analyzed. All images were reconstructed using either filtered backprojection (FBP) with measured attenuation correction (MAC) or iterative reconstruction (IR) with segmented attenuation correction (SAC). In a subset of 15 patients, images were reconstructed using all 4 combinations of IR+SAC, IR+MAC, FBP+SAC, and FBP+MAC. For phantom studies, a sphere containing (18)F-FDG was placed in a water-filled cylinder and the activity concentration of that sphere was measured in FBP and IR reconstructed images using all 4 combinations. Clinical studies were displayed simultaneously and identical regions of interest (ROIs, 50 pixels) were placed in liver, urinary bladder, and tumor tissue in both image sets. SUV max (maximal counts per pixel in ROI) and SUV avg (average counts per pixel) were measured. RESULTS: In phantom studies, measurements from FBP images underestimated the true activity concentration to a greater degree than those from IR images (20% vs. 5% underestimation). In patient studies, SUV derived from FBP images were consistently lower than those from IR images in both normal and tumor tissue: Tumor SUV max with IR+SAC was 9.6 +/- 4.5, with IR+MAC it was 7.7 +/- 3.5, with FBP+MAC it was 6.9 +/- 3.0, and with FBP+SAC it was 8.6 +/- 4.1 (all P < 0.01 vs. IR+SAC). Compared with IR+SAC, SUV from FBP+MAC images were 25%-30% lower. Similar discrepancies were noted for liver and bladder. Discrepancies between measurements became more apparent with increasing (18)F-FDG concentration in tissue. CONCLUSION: SUV measurements in whole-body PET studies are affected by the applied methods for both image reconstruction and attenuation correction. This should be considered when serial PET studies are done in cancer patients. Moreover, if SUV is used for tissue characterization, different cutoff values should be applied, depending on the chosen method for image reconstruction and attenuation correction.     

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.     

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.     

(18)F-fluoride PET for monitoring therapeutic response in Paget's disease of bone.

A prospective study was undertaken to evaluate PET with (18)F-fluoride for monitoring the response to bisphosphonates in Paget's disease of bones. METHODS: Fourteen patients with a monostotic (n = 9) or a polyostotic form (n = 5) of Paget's disease were scanned at baseline and at 1 and 6 mo after the beginning of treatment. Dynamic acquisition and arterial blood sampling were used to calculate the influx constant Ki (by both the Patlak [Ki-PAT] method and the nonlinear regression [Ki-NLR] method). Kinetic modeling was compared with maximal standardized uptake values (SUV(max)) and biochemical markers of bone remodeling. RESULTS: Baseline uptake of (18)F-fluoride by pagetic bones was significantly higher than in normal bones (P < 0.05). One month after the start of treatment, SUV(max), Ki-PAT, Ki-NLR, and K(1) (the unidirectional clearance of fluoride from plasma to the whole of the bone tissue) decreased significantly by 27.8%, 27.9%, 27.5%, and 23.6%, respectively. Biochemical markers were already normalized in 6 of 9 patients with monostotic disease, although all had high (18)F-fluoride uptake values. Six months after the start of treatment, (18)F-fluoride uptake further diminished by 22.3%-25.6%. Biochemical markers were normal in all but 2 patients, although 10 of 14 patients still showed high (18)F-fluoride uptake. One patient did not respond to treatment and maintained high uptake of (18)F-fluoride throughout the study. SUV(max) correlated with both Ki-PAT and Ki-NLR at baseline, 1 mo, and 6 mo (P < 0.05). Moreover, the change of SUV(max) between baseline and 1 mo, as well as between baseline and 6 mo, also correlated with the change of Ki-PAT and Ki-NLR (P < 0.05). CONCLUSION: Our results show that (18)F-fluoride PET can be used to noninvasively and accurately monitor the efficacy of treatment with bisphosphonates in Paget's disease of bones. SUV(max) correlates with Ki-PAT and Ki-NLR and, interestingly, varies in the same manner as kinetic indices. Therefore, the use of SUV(max) could avoid the need for dynamic acquisition and arterial blood sampling and would facilitate the use of whole-body PET in a clinical setting.     

A threshold method to improve standardized uptake value reproducibility

Although standardized uptake values (SUV) are widely used to quantify the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours, there are systematic differences in the way this index is applied by different investigators. The aims of this study were to compare the effects of using maximum or mean region counts in the calculation of SUV and to investigate an alternative technique based on a fixed fraction of the maximum counts. Simulated PET projections of the thorax were generated together with spherical lesions that varied in diameter from 1.6 to 4.8 cm with uptake values of 2, 4 and 8. The lesion SUVs were determined using either the maximum (SUVmax) or mean count (SUVmean) values found in regions circumscribing the lesion. In addition, average values were calculated that only included region pixels that exceeded a selected fraction of maximum value (SUV0.6max or SUV0.75max). These methods were also applied to six clinical 18F-FDG PET studies with a total of 12 lesions. The SUVs for these lesions were determined independently by four observers. Decreases with respect to SUVmax of 57%, 23% and 14% were found for SUVmean, SUV0.6max and SUV0.75max approaches respectively in the simulation study. The variation in SUVmean with region size was 35%, while the SUV0.6max and SUV0.75max was less than 3%. Similar results were obtained for the clinical data. We conclude that the proposed technique produces SUVs that are essentially independent of lesion region size and shape. It is expected that this will provide a more stable and reliable result than current approaches.     

[<Superscript>11</Superscript>C]Choline uptake with PET/CT for the initial diagnosis of prostate cancer: relation to PSA levels,tumour stage and anti-androgenic therapy

PURPOSE: The accuracy of positron emission tomography (PET)/CT with [(11)C]choline for the detection of prostate cancer is not well established. We assessed the dependence of [(11)C]choline maximum standardized uptake values (SUV(max)) in the prostate gland on cell malignancy, prostate-specific antigen (PSA) levels, Gleason score, tumour stage and anti-androgenic hormonal therapy. METHODS: In this prospective study, PET/CT with [(11)C]choline was performed in 19 prostate cancer patients who subsequently underwent prostatectomy with histologic sextant analysis (group A) and in six prostate cancer patients before and after anti-androgenic hormonal therapy (bicalutamide 150 mg/day; median treatment of 4 months; group B). RESULTS: In group A, based on a sextant analysis with a [(11)C]choline SUV(max) cutoff of 2.5 (as derived from a receiver-operating characteristic analysis), PET/CT showed sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 72, 43, 64, 51 and 60%, respectively. In the patient-by-patient analysis, no significant correlation was detected between SUV(max) and PSA levels, Gleason score or pathological stage. On the contrary, a significant (P < 0.05) negative correlation was detected between SUV(max) and anti-androgenic therapy both in univariate (r (2) = 0.24) and multivariate (r (2) = 0.48) analyses. Prostate [(11)C]choline uptake after bicalutamide therapy significantly (P < 0.05) decreased compared to baseline (6.4 +/- 4.6 and 11.8 +/- 5.3, respectively; group B). CONCLUSION: PET/CT with [(11)C]choline is not suitable for the initial diagnosis and local staging of prostate cancer. PET/CT with [(11)C]choline could be used to monitor the response to anti-androgenic therapy.     

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.     

Multiple Myeloma: Molecular Imaging with 11C-Methionine PET/CT--Initial Experience

PURPOSE: To prospectively assess molecular imaging of multiple myeloma (MM) by using the radiolabeled amino acid carbon 11 ((11)C) methionine and positron emission tomography (PET)/computed tomography (CT). MATERIALS AND METHODS: The study was approved by the institutional local ethics committee and the national radiation protection authorities. All patients with MM and control patients gave written informed consent. Nineteen patients with MM (11 women, eight men; age range, 42-64 years) and 10 control patients with hyperparathyroidism without hematologic diseases (six women, four men; age range, 43-75 years) underwent PET/CT 20 minutes after injection of a mean of 1.0 GBq +/- 0.2 (standard deviation) (11)C-methionine. Presence and extent of CT-assessed tumor manifestations and (11)C-methionine bone marrow (BM) uptake were determined on the basis of maximum standardized uptake value (SUV(max)). BM imaging patterns, normal BM, and maximal lesion (11)C-methionine uptake in patients with MM were compared with those in control patients. In two patients with MM, sulfur 35 ((35)S) methionine uptake in freshly isolated BM plasma cells was measured. Values for SUV(max) of groups were compared by using the Mann-Whitney test on a per-patient basis. RESULTS: (35)S-methionine uptake of plasma cells was five- to sixfold higher than in normal BM cells. (11)C-methionine BM uptake in control patients was homogeneous and low. All patients with MM except one with exclusively extramedullary myeloma had (11)C-methionine-positive lesions. Maximal lesion and normal BM (11)C-methionine mean SUV(max) were 10.2 +/- 3.5 and 4.3 +/- 2.0, respectively, and thus were significantly higher than that of BM in the control group (mean, 1.8 +/- 0.3; P < .001). Extramedullary MM was clearly visible in three patients (mean SUV(max), 7.2 +/- 2.4). Additional (11)C-methionine-positive lesions in normal cancellous bone were found in nearly all patients with MM. In pretreated patients with MM, a moderate fraction of osteolytic lesions had no (11)C-methionine uptake. CONCLUSION: On the basis of increased methionine uptake in plasma cells, active MM can be imaged with (11)C-methionine PET/CT.     

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.     

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.     

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.