FDG-PET for the diagnosis of fever of unknown origin: a Japanese multi-center study.

OBJECTIVE: To evaluate the clinical value of 2-[(18)F]fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET) for the diagnosis of fever of unknown origin (FUO), we performed a Japanese multi-center retrospective survey. METHODS: A total of 81 consecutive patients with FUO who underwent FDG-PET at 6 institutions between July 2006 and December 2007 were retrospectively evaluated. FDG uptake was visually evaluated using a 4-grade scale. The efficacy of FDG-PET for the evaluation of FUO, the provision of additional diagnostic information, the clinical impact on therapeutic decisions (4-grade scale), and the diagnostic performance compared with the final diagnosis were evaluated. RESULTS: The diagnostic results were analyzed according to 4 groups of final diagnoses: infection, arthritis/vasculitis/autoimmune/collagen disease (A/V), tumor/granuloma (T/G), and other/unknown (O/U). Sensitivity was highest in T/G, followed by infection, A/V and O/U [100%(7/7), 89%(24/27), 65%(11/17), 0%(0/1) respectively]. Clinical impact and mean FDG score showed the same tendency. Additional information was highest in infection followed by T/G, A/V, and O/U [76%(22/29), 75%(6/8), 43%(9/21), 23%(5/22), respectively]. The O/U group showed a high specificity (84%, 16/19) and accurately excluded active focal inflammatory diseases and malignancy. The use of steroids for the treatment of fever seemed to mask the lesions and modified the results, especially in the A/V group (4 false negatives in 8 steroid users out of 21 A/V patients). The prevalence of each disease in each hospital significantly affected the effectiveness of FDG-PET for the diagnosis of FUO. The mean FDG uptake score and additional information (70%, 31/44 vs. 30%, 11/37, respectively) in national hospital (NH) was significantly higher than in university hospitals (UH). A Grade 3 clinical impact, in which the FDG PET results changed the clinical decision, was seen in 50% (22/44) of the patients in the NH group and 13.5% (5/37) of the patients in the UH group. The sensitivity (91%, 30/33; 63%, 12/19) and specificity (60%, 6/10; 86%, 12/14) of the results in the NH and UH groups differed. The total sensitivity was 81% (42/52), specificity was 75% (18/24). The NH group included a large number of cases with infectious diseases (50%, 23/44), while the UH group included a large number of A/V cases (38%, 14/37) and O/U cases (41%, 15/37). CONCLUSION: FDG-PET for the diagnosis of FUO provided additional diagnostic information and had a high clinical impact, especially among patients with infectious diseases. It was also helpful in cases with unknown or other miscellaneous diseases by allowing the exclusion of focally active diseases. The prevalence of diseases in hospitals significantly affected the effectiveness of FDG-PET for the diagnosis of FUO. FDG-PET is a useful examination providing various degrees of clinical impact for the management of FUO, depending on the characteristics of the patient and the hospital.

Rapid estimation of split renal function in kidney donors using software developed for computed tomographic renal volumetry.

PURPOSE: To evaluate the speed and precision of split renal volume (SRV) measurement, which is the ratio of unilateral renal volume to bilateral renal volume, using a newly developed software for computed tomographic (CT) volumetry and to investigate the usefulness of SRV for the estimation of split renal function (SRF) in kidney donors. METHOD: Both dynamic CT and renal scintigraphy in 28 adult potential living renal donors were the subjects of this study. We calculated SRV using the newly developed volumetric software built into a PACS viewer (n-SRV), and compared it with SRV calculated using a conventional workstation, ZIOSOFT (z-SRV). The correlation with split renal function (SRF) using (99m)Tc-DMSA scintigraphy was also investigated. RESULTS: The time required for volumetry of bilateral kidneys with the newly developed software (16.7±3.9s) was significantly shorter than that of the workstation (102.6±38.9s, p<0.0001). The results of n-SRV (49.7±4.0%) were highly consistent with those of z-SRV (49.9±3.6%), with a mean discrepancy of 0.12±0.84%. The SRF also agreed well with the n-SRV, with a mean discrepancy of 0.25±1.65%. The dominant side determined by SRF and n-SRV showed agreement in 26 of 28 cases (92.9%). CONCLUSION: The newly developed software for CT volumetry was more rapid than the conventional workstation volumetry and just as accurate, and was suggested to be useful for the estimation of SRF and thus the dominant side in kidney donors.

Combining transbronchial biopsy using endobronchial ultrasonography with a guide sheath and positron emission tomography for the diagnosis of small peripheral pulmonary lesions.

To evaluate the combination of transbronchial biopsy (TBB) using endobronchial ultrasonography with a guide sheath (EBUS-GS) and positron emission tomography with fluorodeoxyglucose (FDG-PET) for the diagnosis of small peripheral pulmonary lesions (PPLs) < or = 30 mm in mean diameter. A total of 74 PPLs (69.2%) were diagnosed by TBB using EBUS-GS with X-ray fluoroscopy. Diagnostic yield by FDG-PET was 78.5% for the 107 PPLs examined. Diagnostic yield with the combination of TBB using EBUS-GS and FDG-PET (90.7%) was significantly higher compared with that for each procedure alone. A significant increment in diagnostic yield with this combination was seen for PPLs >20mm and < or = 30 mm and for malignant lesions. Combination of TBB using EBUS-GS and FDG-PET is useful for the diagnosis of small PPLs.

Clinical impact of whole body FDG-PET for recurrent biliary cancer: a multicenter study.

OBJECTIVE: To evaluate the clinical usefulness of positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) in patients with follow-up or suspected recurrent biliary cancer in a multicenter study. METHODS: We performed a retrospective review of 50 patients who underwent FDG-PET (either integrated PET/CT or manual fusion of dedicated PET and CT) scans for post-treatment surveillance of biliary cancer. Recurrence was suspected in 40 of these patients on the basis of tumor marker levels, and/or findings of conventional imaging (group A). Clinical findings in the remaining 10 patients showed them to be disease-free (group B). The diagnostic performance and clinical impact of PET were analyzed. RESULTS: Recurrence was confirmed in 28 out of the 40 patients in group A, and 1 of the 10 patients in group B. Patient-based analysis showed that the sensitivity, specificity, and accuracy of PET for detecting recurrence were 86% (25/29), 91% (19/21), and 88% (44/50), respectively. The one patient with recurrence in group B was correctly interpreted by PET. Positive test likelihood ratio and negative test likelihood ratio were increased from 1.69 to 9.05, and 0.08 to 0.32, respectively, after PET study. The findings of PET resulted in a change of management for 10 out of the 50 patients (20%) by initiating an unplanned treatment strategy (n = 7), by obviating the need for planned diagnostic procedures (n = 2), or by changing the treatment plan (n = 1). CONCLUSION: FDG-PET/CT or PET with CT yielded helpful information in patients with suspected recurrent biliary cancer.

Clinical value and limitations of [11C]-methionine PET for detection and localization of suspected parathyroid adenomas.

PURPOSE: The aim of this study was to assess the clinical value of [(11)C]methionine-PET (MET-PET) for detection and localization of parathyroid adenomas in patients without prior thyroidectomy. METHODS: A retrospective analysis of patients with suspected parathyroid adenomas undergoing imaging with MET-PET was performed. Prior thyroidectomy was an exclusion criterion. Forty-one patients with a total of 49 MET-PET scans were included. MET-PET consisted of whole-body images obtained 15-20 min after injection of 430 +/- 81 MBq of MET using a dedicated PET scanner. Imaging findings were validated by histology or other imaging studies and clinical follow-up on a lesion, side, and location basis. Comparison of PET results to other imaging modalities including ultrasound, MIBI scintigraphy, and morphological imaging [computed tomography (CT) and/or magnetic resonance imaging] and subgroup analysis of primary vs. secondary hyperparathyroidism was performed. RESULTS: Twenty-three of 49 PET scans revealed pathologic findings, whereas 26 of 49 scans were negative. Validation of PET findings for detection and localization of parathyroid adenomas resulted in an overall sensitivity of MET-PET of 54%, 49%, and 35% on a lesion, side, and location basis, respectively. Sensitivity of MET-PET was inferior compared to ultrasonography (50% vs. 93%), MIBI scintigraphy (53% vs. 74%) and morphological imaging (52% vs. 74%). Subgroup analysis revealed higher sensitivity for MET-PET in secondary HPT (sHPT) than primary HPT (pHPT; 62% vs. 43%; side basis). CONCLUSIONS: In patients with initial diagnosis of hyperparathyroidism and no prior thyroidectomy, the sensitivity of MET-PET for detection and localization of parathyroid adenomas is markedly lower compared to previous reports. While performance was better in sHPT, we believe that MET-PET cannot be recommended for pHPT localization in this clinically relevant subcollective. The clinical value of MET/PET in patients with hyperparathyroidism should be further investigated in a prospective study utilizing anatometabolic imaging with a PET/CT device.

Assessment of cervical lymph node metastases using FDG-PET in patients with head and neck cancer.

OBJECTIVE: To evaluate the diagnostic accuracy of fluorodeoxyglucose positron emission tomography (FDG-PET) relative to computed tomography (CT) for detecting metastatic cervical lymph nodes in patients with squamous cell carcinoma of the head and neck (HNSCC), and to ascertain the factors that affect this accuracy. METHODS: A total of 1076 lymph nodes obtained from 35 neck dissections in 26 HNSCC patients who preoperatively underwent both FDG-PET and CT were retrospectively analyzed. For pathological metastatic lymph nodes, the lymph node size (short-axis diameter), the ratio of intranodal tumor deposits, and the size of intranodal tumor deposits (maximum diameter of metastatic foci in each lymph node) were histologically recorded. RESULTS: Forty-six lymph nodes from 23 neck sides were pathologically diagnosed metastases. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FDG-PET evaluated individually per neck side were 74%, 92%, 80%, 94%, and 65%, respectively, whereas those of CT were 78%, 58%, 71%, 78%, and 58%, respectively. FDG-PET detected 100% of metastatic lymph nodes > or =10 mm, intranodal tumor deposits > or =9 mm, and intranodal tumor deposits with a ratio >75%, whereas no nodes or tumor deposits smaller than 5 mm were detected. The spatial resolution limitations of FDG-PET were responsible for 16 of 20 (80%) false-negative PET results in lymph nodes. CONCLUSIONS: FDG-PET is a useful tool for preoperative evaluation of the neck because it accurately detects metastatic lymph nodes > or =10 mm and has fewer false-positive cases than CT. The high specificity of FDG-PET for lymph node metastases may play an important role in avoiding unnecessary neck dissection.

Usefulness of 11C-methionine for differentiating tumors from granulomas in experimental rat models: a comparison with 18F-FDG and 18F-FLT.

UNLABELLED: Many clinical PET studies have shown that increased (18)F-FDG uptake is not specific to malignant tumors. (18)F-FDG is also taken up in inflammatory lesions, particularly in granulomatous lesions such as sarcoidosis or active inflammatory processes after chemoradiotherapy, making it difficult to differentiate malignant tumors from benign lesions, and is the main source of false-positive (18)F-FDG PET findings in oncology. These problems may be overcome by multitracer studies using 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) or l-(11)C-methionine. However, (18)F-FLT or (11)C-methionine uptake in granulomatous lesions remains unclarified. In this study, the potentials of (18)F-FLT and (11)C-methionine in differentiating malignant tumors from granulomas were compared with (18)F-FDG using experimental rat models. METHODS: Dual-tracer tissue distribution studies using (18)F-FDG and (3)H-FLT (groups I and III) or (18)F-FDG and (14)C-methionine (groups II and IV) were performed on rats bearing both granulomas (Mycobacterium bovis bacillus Calmette-Guérin [BCG]-induced) and hepatomas (KDH-8-induced) (groups I and II) or on rats bearing both turpentine oil-induced inflammation and hepatomas (groups III and IV). One hour after the injection of a mixture of (18)F-FDG and (3)H-FLT or of (18)F-FDG and (14)C-methionine, tissues were excised to determine the radioactivities of (18)F-FDG, (3)H-FLT, and (14)C-methionine (differential uptake ratio). RESULTS: Mature epithelioid cell granuloma formation and massive lymphocyte infiltration were observed in the granuloma tissue induced by BCG, histologically similar to sarcoidosis. The granulomas showed high (18)F-FDG uptake comparable to that in the hepatomas (group I, 8.18 +/- 2.40 vs. 9.13 +/- 1.52, P = NS; group II, 8.43 +/- 1.45 vs. 8.91 +/- 2.32, P = NS). (14)C-Methionine uptake in the granuloma was significantly lower than that in the hepatoma (1.31 +/- 0.22 vs. 2.47 +/- 0.60, P < 0.01), whereas (3)H-FLT uptake in the granuloma was comparable to that in the hepatoma (1.98 +/- 0.70 vs. 2.30 +/- 0.67, P = NS). Mean uptake of (18)F-FDG, (3)H-FLT, and (14)C-methionine was markedly lower in the turpentine oil-induced inflammation than in the tumor. CONCLUSION: (14)C-Methionine uptake was significantly lower in the granuloma than in the tumor, whereas (18)F-FDG and (3)H-FLT were not able to differentiate granulomas from tumors. These results suggest that (14)C-methionine has the potential to accurately differentiate malignant tumors from benign lesions, particularly granulomatous lesions, providing a biologic basis for clinical PET studies.

Comparison of MET-PET and FDG-PET for differentiation between benign lesions and lung cancer in pneumoconiosis.

OBJECTIVE: The aim of this study was to evaluate and compare the ability of C-11-methionine (MET) and F-18 fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) to diagnose lung cancer in patients with pneumoconiosis. METHODS: Twenty-six subjects underwent both whole-body MET-PET and FDG-PET on the same day. The first group was a lung cancer group, which consisted of 15 patients, and included those with pneumoconiosis with increased nodules (13 cases), hemoptysis (1 case), and positive sputum cytology (1 case). The second group was a no-malignancy control group, consisting of 11 patients with pneumoconiosis. RESULTS: Significant correlations between nodule size and the maximum standardized uptake value (SUV(max)) of the two PET tracers were observed in the control group. The larger the nodule size, the greater were the amounts of these tracers accumulated (MET: r = 0.771, P < 0.0001; FDG: r = 0.903, P < 0.0001). The SUV(max) of MET was significantly lower than that of FDG in the pneumoconiotic nodules (P < 0.0001). Lung cancer was found in 5 of 19 nodules (two with adenocarcinoma, one with squamous cell carcinoma, one with small cell carcinoma, and one with large cell carcinoma) in the first group. As for nodules equal to or less than 3 cm in diameter, the SUV(max) of MET was significantly higher in the lung cancer than in the pneumoconiotic nodules, with 3.48 +/- 1.18 (mean +/- SE) for the lung cancer and 1.48 +/- 0.08 for the pneumoconiotic nodules (P < 0.01), similar to the SUV(max) of FDG, with 7.12 +/- 2.36 and 2.85 +/- 0.24 (P < 0.05), respectively. On the basis of the criteria for the control group, FDG and MET identified lung cancer with sensitivities of 60% and 80%, specificities of 100% and 93%, accuracies of 90% and 90%, positive predictive values of 100% and 80%, and negative predictive values of 88% and 93%, respectively. CONCLUSIONS: Our results indicate that nodules with an intense uptake of MET and FDG relative to their size should be carefully observed because of a high risk for lung cancer.

Whole-body iodine-131 metaiodobenzylguanidine imaging for detection of bone metastases in patients with paraganglioma: comparison with bone scintigraphy.

Iodine-131 metaiodobenzylguanidine ((131)I-MIBG) therapy is an effective treatment for patients with malignant paraganglioma for which surgical resection is not indicated. We performed high-dose (131)I-MIBG therapy on two patients with malignant paraganglioma and multiple bone metastases. The bone metastases were diagnosed by magnetic resonance imaging (MRI). Metastatic bone lesions were evaluated by whole-body (131)I-MIBG imaging and bone scintigraphy. Whole-body (131)I-MIBG imaging showed extensive metastatic bone lesions, whereas conventional bone scintigraphy did not. There was a remarkable discrepancy between (131)I-MIBG imaging and bone scintigraphy in the diagnosis of metastatic bone lesions of malignant paraganglioma in our two patients. High-dose (131)I-MIBG imaging may detect early stages of bone metastases, compared with bone scintigraphy, in patients with malignant paraganglioma.