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It was previously reported that tetraiodothyroacetic acid (tetrac) inhibits angiogenesis by binding to the cell surface receptor for thyroid hormone on integrin α V β 3 . Therefore, we synthesized and evaluated two 64 Cu-labeled tetrac derivatives and a Cy5.5-labeled tetrac derivative for tumor angiogenesis imaging. Tetrac was structurally modified to conjugate with 1,4,7,10-tetraazacyclododecane-N,N',N″,N″'-tetraacetic acid (DOTA) via its hydroxy or carboxylic acid end, and the resulting DOTA-conjugated tetrac derivatives were then labeled with 64 Cu. Tetrac was also conjugated with Cy5.5 via its carboxylic acid end. All three tetrac derivatives (1-3) exhibited greater inhibitory activity than tetrac against endothelial cell tube formation. The U87MG cell binding of [ 64 Cu]2 showed a time-dependent increase over 24 h and it was inhibited by 38% at 4 h in the presence of tetrac, indicating specificity of [ 64 Cu]2 to the thyroid hormone receptor site on integrin α V β 3 . Positron emission tomography (PET) images of U87MG tumor-bearing mice injected with [ 64 Cu]1 and [ 64 Cu]2 revealed that high radioactivity accumulated in the tumors, and that the tumor uptake and tumor-to-nontarget uptake ratio were higher in small tumors than in large tumors. In addition, the Cy5.5-labeled tetrac derivative (3) displayed a strong near-infrared (NIR) signal in the tumors. Taken together, these results suggest that these ligands hold promise as imaging agents for visualization of tumor angiogenesis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: We conducted this study to investigate the value of early metabolic responses assessed by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in predicting prognosis and monitoring treatment response in patients with unresectable thymic epithelial tumors (TETs)., Patients and Methods: Study subjects were selected from the prospective dataset of a phase II clinical trial for cisplatin plus Cremorphor EL-free paclitaxel. A total of thirty patients with unresectable TETs who underwent baseline and early post treatment scan after two cycles of chemotherapy were enrolled (22 Male; mean age 55.0±15.0years). Metabolic parameters including metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the tumor lesions were measured., Results: Multivariate analysis using Cox proportional hazards regression model showed that percent decrease of MTV (HR=0.995 by 1% decrease, P=0.037) and TLG (HR=0.996 by 1% decrease, P=0.044) were significant predictors of progression-free survival (PFS). Receiver operating characteristic curve identified an 88.0% decrease in MTV and a 92.0% decrease in TLG as the optimal cut-off value for disease progression. Responders with ≥88% of ΔMTV and ≥92% of Δ TLG had significantly longer PFS than non-responders (P=0.012, 0.026, respectively)., Conclusion: The percent decrease in MTV and TLG of tumor lesions measured by early post treatment FDG PET/CT significantly associated with disease progression in this study. Early metabolic response based on these volumetric parameters has the potential to monitor treatment response and predict prognosis in patients with unresectable TETs., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Purpose To describe clinical, computed tomographic (CT), and positron emission tomographic (PET) features, correlation of CT and pathologic results, and survival of patients with pulmonary intravascular lymphomatosis. Materials and Methods The institutional review board approved this retrospective study with waiver of patient consent. Forty-two patients with pulmonary intravascular lymphomatosis were identified, 11 (26%) of whom showed lung involvement. CT features were correlated with histopathologic results. Clinical and survival outcomes were compared between patients with and those without pulmonary involvement by adopting the χ(2), Student t, or Kaplan-Meier analysis with log-rank tests. Results At clinical presentation, all 11 patients showed B symptoms (systemic symptoms of fever, night sweats, and weight loss), 10 had respiratory and four had neurologic symptoms, and two had skin lesions. Patients received cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with (n = 5) or without (n = 6) rituximab, and seven (64%) patients died. Patients with lung involvement showed reduced overall and recurrence-free survival (median; 10.8 and 18.9 months, respectively) compared with those without lung involvement (median, 18.4 and 31.0 months, respectively) (P = .338 and .065, respectively). The most common CT abnormality was bilateral ground-glass opacity (GGO, n = 10), with increased fluorodeoxyglucose uptake at PET/CT (seven of seven patients). GGO correlated histopathologically with the expanded alveolar septal vasculatures and perivascular spaces filled with neoplastic lymphoid cells. Conclusion Pulmonary intravascular lymphomatosis appeared as bilateral GGO on CT images, with increased fluorodeoxyglucose uptake on PET/CT images. GGO on CT images correlated with the area of expanded alveolar septae because of distended vessels filled with neoplastic lymphoid cells. (©) RSNA, 2016 Online supplemental material is available for this article.

Little is known about prognostic factors in epithelioid hemangioendothelioma (EHE). We aimed to identify prognostic factors among various clinicopathologic and imaging features of thoracic EHEs.Forty-two patients (male:female = 20:22; median age, 49 years) of EHEs with (n = 19) and without (n = 23) thoracic involvement were included. We reviewed electronic medical records for clinical information and computed tomography (CT) features for thoracic involvement. Differences in demographics and survival outcomes of patients with and without thoracic involvement were assessed. We also estimated overall survival.The most common pattern of thoracic involvement was multiple pulmonary nodules (n = 10), followed by parenchymal tumor with pleural invasion (n = 4), reticulonodular opacities (n = 3), and diffuse pleural thickening (n = 2). No significant difference in survival was found between the thoracic EHE group and nonthoracic EHE group (P = 0.68). Among 4 different thoracic involvement types, the lung multinodular pattern tended to demonstrate longer median survival (8.5 months) than other patterns, whereas the shortest median survival (1 month) was observed for the nodule/mass with pleural involvement pattern (P = 0.038).CT manifestations of thoracic EHEs are classified into 4 patterns, of which lung multinodular pattern is associated with longer survival. Survival is not different between patients with and without thoracic involvement., Competing Interests: The authors have no conflicts of interest to disclose.

Purpose: We investigated the capacity of F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) to differentially diagnose immunoglobulin G4-related disease (IgG4-RD) in clinically suspected patients., Materials and Methods: Subjects were 94 clinically suspected patients who had tissue IgG4 staining (n = 85) or serum IgG4 greater than 135 mg/dL (n = 9) and underwent FDG PET/CT within 40 days. Clinical, serologic, pathological, and PET/CT findings were analyzed. Binary logistic regression analysis was performed to assess the diagnostic performance of PET/CT., Results: Final diagnosis was IgG4-RD in 28, malignancy in 29, IgG4-unrelated inflammation in 35, and undetermined cause in 2 subjects. Patients with IgG4-RD had lower maximum standardized uptake value (SUVmax) of FDG uptake in lesions (4.6 ± 1.7 vs 7.1 ± 5.0) and higher submandibular gland SUVmax (2.8 ± 1.0 vs 2.3 ± 0.6) and were more likely to have diffuse/heterogeneous uptake pattern (78.6% vs 54.8%). The relation between SUVmax of lesions and histopathological findings was weak. On binary logistic regression analysis, lesion SUVmax, submandibular gland SUVmax, and multiorgan involvement were significant predictors of IgG4-RD and provided an area under the receiver operating characteristics curve of 0.824. With optimum criteria, FDG PET/CT had a sensitivity of 85.7% and specificity of 66.1% for diagnosing IgG4-RD., Conclusions: FDG PET/CT findings may have the capacity to potentially differentiate IgG4 RD from other diseases in clinically suspected patients.

Unlabelled: The usefulness of (18)F-FDG PET in gastric cancer recurrence is limited by low sensitivity. Given that detectability by PET is dependent on the tumor's metabolic characteristics, we tested whether the performance of PET for gastric cancer recurrence is enhanced in patients with (18)F-FDG-avid primary tumors., Methods: Three hundred sixty-eight patients with advanced gastric cancer underwent (18)F-FDG PET/CT for initial staging and for recurrence surveillance after curative surgery. On initial PET/CT, primary tumors were (18)F-FDG-avid if they displayed focal uptake with an SUVmax 4 or more. Follow-up (18)F-FDG PET/CT was evaluated for recurrent disease., Results: On initial PET/CT, the primary tumor was (18)F-FDG-avid in 236 of 368 (64.1%) and nonavid in 132 patients (35.9%). During follow-up for 18.9 ± 13.3 mo, 72 patients (19.6%) had recurrence. Of the 63 PET scans with recurrence, 42 (66.7%) and 21 (33.3%) were scans of patients with (18)F-FDG-avid and nonavid primary tumors, respectively. PET sensitivity was higher in scans of patients with (18)F-FDG-avid than nonavid tumors for all recurrences (81.0% vs. 52.4%;P= 0.018) and nonanastomosis site recurrences (82.1% vs. 47.4%; P= 0.006). The sensitivity for detecting peritoneal recurrence was also higher for the avid tumor group. PET specificity was similarly high (97.1% and 97.5%) for both groups. Adding cell type and Lauren classification to tumor(18)F-FDG avidity further enhanced PET sensitivity., Conclusion: Surveillance (18)F-FDG PET/CT after resection of gastric cancer has significantly higher sensitivity in patients with (18)F-FDG-avid primary tumors and may have greater value in this group., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Purpose: We investigated the significance of unexpected focal pyriform sinus FDG uptake and determined the ability of PET/CT parameters to identify malignancy., Materials and Methods: FDG PET/CT reports of 56,585 consecutive subjects were retrospectively reviewed, and 281 cases (0.50%) with focal pyriform sinus uptake were included. PET images were assessed for maximum standardized uptake values (SUVmax) and asymmetric indices of FDG activity, and CT images were evaluated for pyriform sinus narrowing. The final diagnosis was determined by tissue biopsy, laryngoscopy, radiological findings, and clinical follow-up., Results: Among the 281 subjects, final diagnosis was pyriform sinus malignancy in 29 (10.3%) and benignity in 215 cases (76.5%). Malignant lesions had significantly higher SUVmax (9.13 ± 3.64 vs. 3.53 ± 1.01) and asymmetric index (4.16 ± 1.81 vs. 1.54 ± 0.39) compared to benign causes. Patients with malignant lesions also had higher cervical lymph node SUVmax (6.66 ± 8.79 vs. 2.76 ± 2.46, all P < 0.001). Lesion SUVmax ≥4.24 identified malignancy with a sensitivity of 93.1% and specificity of 86.5%. Asymmetric index ≥1.81 had a sensitivity of 100% and specificity of 89.7%., Conclusion: Incidentally identified focal pyriform sinus uptake on FDG PET/CT should be evaluated for possible malignancy in the presence of high SUVmax or asymmetric index.

We assessed the association between nonalcoholic fatty liver disease (NAFLD) and carotid artery inflammation measured by (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography. Participants were 755 consecutive otherwise healthy adult males who underwent a general health screening program. Carotid FDG uptake, represented as maximum target-to-background ratio, was increased with mild (n = 237; 1.61 ± 0.14; P = .033) and moderate NAFLD (n = 145; 1.63 ± 0.16; P = .005) compared with controls (n = 373; 1.58 ± 0.15). In patients aged >50 years, moderate NAFLD was the only independent risk factor for high carotid FDG uptake (odds ratio, 2.12; 95% confidence interval, 1.10-4.07; P = .001). Apparently healthy adult males with NAFLD have elevated carotid FDG uptake as well as increased carotid intima-media thickness, suggesting that they may be at an increased risk of having inflammatory atherosclerotic plaques in the carotid arteries., (© The Author(s) 2014.)

Background: We evaluated the prognostic value of volume-based metabolic positron emission tomography (PET) parameters in patients with small cell lung cancer (SCLC) compared with other factors., Methods: The subjects were 202 patients with pathologically proven SCLC who underwent pretreatment 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT). Volumetric metabolic parameters of intrathoracic malignant hypermetabolic lesions, including maximum and average standardized uptake value, sum of metabolic tumor volume (MTV), and sum of total lesion glycolysis (TLG) were measured., Results: 164 patients had died during follow-up (median 17.4 months) and median overall survival was 14 months. On univariate survival analysis, age, stage, treatment modality, sum of MTV (cutoff = 100 cm3), and sum of TLG (cutoff = 555) were significant predictors of survival. There was a very high correlation between the sum of MTV and the sum of TLG (r = 0.963, P < 0.001). On multivariate survival analysis, age (HR = 1.04, P < 0.001), stage (HR = 2.442, P < 0.001), and sum of MTV (HR = 1.662, P = 0.002) were independent prognostic factors. On subgroup analysis based on limited disease (LD) and extensive disease (ED), sum of MTV and sum of TLG were significant prognostic factors only in LD., Conclusion: Both sum of MTV and sum of TLG of intrathoracic malignant hypermetabolic lesions are important independent prognostic factors for survival in patients with SCLC, in addition to age and clinical stage. However, it may be more useful in limited disease rather than in extensive disease.

Background: Subjects with fatty liver disease (FLD) can show increased hepatic 2-deoxy-2-((18)F)fluoro-D-glucose (FDG) uptake, but the role of hepatic inflammation has not been explored., Aims: We investigated whether hepatic inflammatory response, as implicated by elevated serum markers, is associated with increased liver FDG uptake in FLD., Methods: Liver sonography and FDG positron emission tomography was performed in 331 asymptomatic men with nonalcoholic FLD (NAFLD), 122 with alcoholic FLD (AFLD), and 349 controls. Mean standard uptake value (SUV) of liver FDG uptake was compared to cardiac risk factors and serum markers of liver injury., Results: Hepatic FDG mean SUV was increased in NAFLD (2.40 ± 0.25) and AFLD groups (2.44 ± 0.25) compared to controls (2.28 ± 0.26; both P < 0.001). Both FLD groups also had higher serum γ-glutamylranspeptidase (GGT), triglyceride (TG), hepatic transaminases, and LDL. High GGT and TG levels were independent determinants of increased FDG uptake for both FLD groups. Hepatic mean SUV significantly increased with high compared to low GGT for NAFLD (2.48 ± 0.28 vs. 2.37 ± 0.24), AFLD (2.51 ± 0.27 vs. 2.39 ± 0.23), and control groups (2.39 ± 0.22 vs. 2.26 ± 0.26). High TG increased hepatic mean SUV in AFLD and control groups. Furthermore, serum GGT and TG levels significantly correlated to hepatic mean SUV in all three groups., Conclusions: Hepatic FDG uptake is closely associated with elevated TG and GGT regardless of the presence of FLD. Thus, inflammation response may play a major role in increased hepatic glucose uptake.

Purpose: Vascular endothelial growth factor (VEGF) is a crucial regulator of angiogenesis. In this study, we labeled VEGF₁₂₁ with (68)Ga using a hydrophilic chelating agent, NODAGA and evaluated the resulting (68)Ga-NODAGA-VEGF₁₂₁ for in vivo imaging of VEGF receptor (VEGFR) expression., Methods: NODAGA-VEGF₁₂₁ was prepared and its binding affinity for VEGFR2 was measured using (125)I-VEGF₁₂₁. (68)Ga-NODAGA-VEGF₁₂₁ was prepared by labeling NODAGA-VEGF₁₂₁ with (68)GaCl3 followed by purification using a PD-10 column. Human aortic endothelial cell (HAEC) binding studies of (68)Ga-NODAGA-VEGF₁₂₁ were performed at 37°C for 4 h. MicroPET imaging followed by biodistribution studies were performed in U87MG tumor-bearing mice injected with (68)Ga-NODAGA-VEGF₁₂₁. Immunofluorescence staining of the tumor tissues was performed to verify VEGFR2 expression., Results: Binding affinity of NODAGA-VEGF₁₂₁ for VEGFR2 was found to be comparable to that of VEGF₁₂₁. (68)Ga-NODAGA-VEGF₁₂₁ was prepared in 47.8% yield with specific activity of 3.4 GBq/mg. (68)Ga-NODAGA-VEGF₁₂₁ was avidly taken up by HAECs with a time-dependent increase from 9.88 %ID at 1 h to 20.86 %ID at 4h. MicroPET imaging of mice demonstrated high liver and spleen uptake with clear visualization of tumor at 1h after injection. ROI analysis of tumors revealed 2.53 ± 0.11 %ID/g at 4 h after injection. In the blocking study, tumor uptake was inhibited by 29% at 4 h. Subsequent biodistribution studies demonstrated tumor uptake of 2.38 ± 0.15 %ID/g. Immunofluorescence staining of the tumor tissues displayed high level of VEGFR2 expression., Conclusions: These results demonstrate that (68)Ga-NODAGA-VEGF₁₂₁ led to VEGFR-specific distribution in U87MG tumor-bearing mice. This study also suggests that altered physicochemical properties of VEGF₁₂₁ after radiolabeling may affect biodistribution of the radiolabeled VEGF₁₂₁., (© 2013.)

Purpose: To investigate the prognostic role of metabolic response by the use of serial sets of positron emission tomography/computed tomography (PET/CT) in patients with cervical cancer who were treated with concurrent chemoradiation therapy (CCRT)., Methods and Materials: A total of 60 patients who were treated with CCRT between February 2009 and December 2010 were analyzed. Three sequential PET/CT images were acquired for each patient: pre-CCRT, during-CCRT at 4 weeks of CCRT, and 1 month post-CCRT PET/CT. Metabolic responses were assessed qualitatively. The percentage changes in the maximum values of standardized uptake value (ΔSUV(max)%) from the PET/CT images acquired pre-CCRT and during-CCRT were calculated. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether ΔSUV(max)% could predict complete response (CR) on the post-CCRT PET/CT and to identify the best cutoff value. Prognostic factors of progression-free survival (PFS) were analyzed., Results: During-CCRT PET/CT showed that 8 patients (13%) had CR, and the other 52 patients (87%) had partial response (PR). On the post-CCRT PET/CT, 43 patients (73%) had CR, 12 patients (20%) had PR, and 4 patients (7%) had progressive disease. The average SUV(max) in primary tumors was 16.3 (range, 6.4-53.0) on the pre-CCRT PET/CT images and 5.3 (range, 0-19.4) on the during-CCRT PET/CT images. According to ROC curve analysis, ΔSUV(max)% could predict CR response on post-CCRT PET/CT (P<.001, cutoff value of 59.7%). In all patients, the PFS rate was 71.9% at 2 years. Multivariate analysis showed that ΔSUV(max)% ≥60% (P=.045) and CR response on the post-CCRT PET/CT (P=.012) were statistically significant predictors of PFS., Conclusion: Metabolic responses on the during-CCRT images at 4 weeks of treatment and 1-month post-CCRT PET/CT images may predict treatment outcomes in patients with cervical cancer. ΔSUV(max)% ≥60% at 4 weeks of CCRT may predict CR response on 1-month post-CCRT PET/CT and also PFS., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To correlate the results of histopathologic subtyping and grading of lung adenocarcinoma with maximum standardized uptake values (SUVmax) on positron emission tomography (PET)/computed tomography and apparent diffusion coefficient (ADC) values on diffusion-weighted MRI (DWI)., Materials and Methods: Forty-three patients were included. The SUVmax and mean ADC values of tumors were measured and correlated with the histologic subtypes and grades of lung adenocarcinomas based on the IASLC/ATS/ERS classification scheme. Disease-free survival (DFS) was estimated by using the Kaplan-Meier method, and the log-rank test was used to evaluate differences among three histologic grades or subgroups classified with imaging biomarker study results., Results: Five (12.5%) tumors belonged to low grade, 30 (70%) to intermediate grade, and 8 (18.5%) to high grade, and patients with low-grade histology had lower risk of recurrence than those with intermediate- or high-grade histology (P = 0.048). A significant difference in SUVmax and mean ADC values was observed among three histologic grades (Ps < 0.001). Regarding DFS, lower metabolic (PET) activity or higher functional (DWI) diffusivity showed longer DFS. When patients (n = 30; 70% of patients) with intermediate histologic grade were subgrouped in consideration of both SUVmax and mean ADC results, combining metabolic and functional criteria helped stratify patients more precisely (P = 0.006)., Conclusion: SUVmax and mean ADC value correlate well with the histologic grades in lung adenocarcinomas, and combining both imaging biomarker study results leads to more useful stratification of patients into different prognostic subsets than the results of each study., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: We assessed factors affecting fluorine F 18 fluorodeoxyglucose (F-FDG) uptake of metastatic lymph nodes (LNs) in advanced gastric cancer (AGC) due to low F-FDG uptake of metastatic LNs in gastric cancer., Methods: Retrospective analyses were performed on 31 patients with AGCs who underwent preoperative F-FDG positron emission tomography (PET) and subsequent gastrectomy. Metastatic LNs were compared with primary tumors (on a one-to-one basis) with respect to maximum standardized uptake values, glucose transporter type 1 (GLUT-1) expression, proliferation indices (using Ki-67), microvessel density, and lymphatic vessel density., Results: Maximum standardized uptake values of metastatic LNs were significantly correlated with % GLUT-1 expression (ρ = 0.80, P < 0.0001) and Ki-67 labeling index (ρ = 0.57, P = 0.001) in LNs. These uptake values were also significantly correlated with SUVs (ρ = 0.54; P = 0.002), % GLUT-1 expression (ρ = 0.71, P < 0.0001), and Ki-67 labeling index (ρ = 0.43, P = 0.019) in primary tumors. In multiple regression analysis, only % GLUT-1 expression in primary tumors and metastatic LNs were significant factors in predicting maximum standardized uptake value of metastatic LNs., Conclusions: In AGCs, GLUT-1 expression and Ki-67 labeling index are important factors in predicting F-FDG uptake by metastatic LNs.

We have developed a vascular endothelial growth factor 121 (VEGF121)-based, dual positron emission tomography (PET)/optical imaging probe for monitoring VEGF receptor (VEGFR) expression using a streptavidin (SAv)-biotin platform. (64)Cu-1,4,7,10-tetraazacyclododecane-N,N',N″,N'″-tetraacetic acid (DOTA)-conjugated Alexa Fluor 680 (AF)-SAv/biotin-PEG-VEGF121 ((64)Cu-labeled dual probe) was prepared with a radiochemical yield of 31.40 ± 3.30% and was stable for 24 h in serum. A human aortic endothelial cell binding study showed avid, time-dependent cellular uptake of the (64)Cu-labeled dual probe. MicroPET imaging of U87MG tumor-bearing mice injected with (64)Cu-labeled dual probe showed rapid, high accumulation of radioactivity in tumors, which reached 3.90 ± 0.17 %ID/g and 4.93 ± 0.80 %ID/g at 1 and 22 h after injection, respectively. Subsequent optical imaging of mice revealed strong fluorescence signals in tumors. Biodistribution studies performed after in vivo imaging demonstrated tumor uptake of 4.19 ± 0.14 %ID/g. Tumor uptake was blocked by 28% in the presence of VEGF121, confirming the VEGFR specificity of the (64)Cu-labeled dual probe. Ex vivo microPET images of major tissues showed the signal intensities consistent with optical images of the corresponding tissues. Moreover, it was shown that tumor uptake of the (64)Cu-labeled dual probe was not due to non-specific uptake by (64)Cu-DOTA-conjugated AF-SAv (tumor uptake; 1.57 ± 0.09 %ID/g). Taken together, these results suggest that the (64)Cu-labeled dual probe is a promising candidate for dual PET/optical imaging of VEGFR expression., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Unlabelled: The utility of (18)F-FDG PET/CT in patients with nasal-type natural killer (NK)/T-cell lymphoma has not been established. Therefore, we evaluated the role of (18)F-FDG PET/CT for determining cancer staging by comparing its results to those of conventional staging methods (CSMs) (physical examination, CT with intravenous contrast, biopsies from primary sites, and bone marrow examinations) in patients with nasal-type NK/T-cell lymphoma., Methods: In this study, 52 consecutive patients (34 men, 18 women; mean age, 49.4 y) with newly diagnosed nasal-type NK/T-cell lymphoma were studied. Anatomic regions (n = 1,300; 16 nodal and 9 extranodal regions per patient) were assessed with an (18)F-FDG PET/CT scan and with CSMs, and each anatomic region was classified as positive or negative for malignancy. Biopsy and clinical follow-up, including additional imaging studies, were used as the gold standard for diagnosis., Results: Of the 59 nodal and 71 extranodal anatomic regions that were truly positive for malignancy, (18)F-FDG PET/CT detected 58 nodal and 69 extranodal. CSMs, however, detected only 44 of the nodal and 61 of the extranodal anatomic regions that were positive for malignancy (nodal comparison of PET/CT vs. CSMs, P < 0.001; extranodal comparison of PET/CT vs. CSMs, P = 0.008). PET/CT scans exhibited a significantly better sensitivity (97.7% vs. 80.7%, P < 0.001) than CSMs for the detection of malignant lesions. PET/CT findings altered the original staging category for 12 patients (21.2%) and affected treatment planning in 23 cases (44.2%)., Conclusion: Our study demonstrated that (18)F-FDG PET/CT scanning is a valuable modality for staging and treatment planning in patients with nasal-type NK/T-cell lymphoma.

Background: The objective of this study was to assess whether coregistered whole brain (WB) magnetic resonance imaging-positron emission tomography (MRI-PET) would increase the number of correctly upstaged patients compared with WB PET-computed tomography (PET-CT) plus dedicated brain MRI in patients with nonsmall cell lung cancer (NSCLC)., Methods: From January 2010 through November 2011, patients with NSCLC who had resectable disease based on conventional staging were assigned randomly either to coregistered MRI-PET or WB PET-CT plus brain MRI (ClinicalTrials.gov trial NCT01065415). The primary endpoint was correct upstaging (the identification of lesions with higher tumor, lymph node, or metastasis classification, verified with biopsy or other diagnostic test) to have the advantage of avoiding unnecessary thoracotomy, to determine appropriate treatment, and to accurately predict patient prognosis. The secondary endpoints were over staging and under staging compared with pathologic staging., Results: Lung cancer was correctly upstaged in 37 of 143 patients (25.9%) in the MRI-PET group and in 26 of 120 patients (21.7%) in the PET-CT plus brain MRI group (4.2% difference; 95% confidence interval, -6.1% to 14.5%; P = .426). Lung cancer was over staged in 26 of 143 patients (18.2%) in the MRI-PET group and in 7 of 120 patients (5.8%) in the PET-CT plus brain MRI group (12.4% difference; 95% confidence interval, 4.8%-20%; P = .003), whereas lung cancer was under staged in 18 of 143 patients (12.6%) and in 28 of 120 patients (23.3%), respectively (-10.7% difference; 95% confidence interval, -20.1% to -1.4%; P = .022)., Conclusions: Although both staging tools allowed greater than 20% correct upstaging compared with conventional staging methods, coregistered MRI-PET did not appear to help identify significantly more correctly upstaged patients than PET-CT plus brain MRI in patients with NSCLC., (Copyright © 2013 American Cancer Society.)

Background: The role of (18) F-fluorodeoxyglucose positron emission tomography/computed tomography ((18) F-FDG PET/CT) in evaluating pulmonary artery lesions has not yet been established. The purpose of this study is to evaluate the usefulness of (18) F-FDG PET/CT imaging in differentiating malignant from benign pulmonary artery (PA) lesions., Methods: In this retrospective study, 18 subjects with 26 low-attenuated filling defects suspicious for PA malignancy on contrast-enhanced chest CT were enrolled; all of whom subsequently underwent (18) F-FDG PET/CT. The maximum standardized uptake value (SUVmax) for all PA lesions, defined as the (18) F-FDG uptake, was measured. The final diagnosis was then determined by pathological findings, follow-up chest CT or clinical follow-up, and compared with the PET imaging., Results: In total, 6 PA sarcomas, 5 tumour embolism, and 15 pulmonary thromboembolism (PTE) occurred in this cohort. Not only was the SUVmax of the malignant PA lesions (10.2 ± 10.8) was significantly higher than that associated with PTE (1.7 ± 0.3; P < 0.001), no overlap occurred between groups. Conversely, no statistically significant difference in SUVmax occurred between PA sarcomas (12.8 ± 14.7) and tumour embolism (7.0 ± 1.32; P = 1.000)., Conclusions:  (18) F-FDG PET/CT is a useful imaging modality for differentiating malignant from benign PA lesions in patients with inconclusive low-attenuation filling defects on contrast-enhanced chest CT., (© 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.)

Objective: To evaluate the prognostic significance and predictive performance of volume-based parameters of F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in early-stage non-small cell lung cancer (NSCLC)., Background: Although surgical resection remains the optimal treatment for early-stage NSCLC, approximately 40% of patients with stage I and 60% of patients with stage II NSCLC relapse and die within 5 years after curative resection. Therefore, identification of additional prognostic biomarkers is needed to develop risk-adapted treatment strategies., Methods: We retrospectively reviewed 529 consecutive patients with pathologically proven early-stage NSCLC who underwent preoperative F-FDG PET/CT. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the primary tumors were measured. Overall survival (OS) and disease-free survival (DFS) were assessed by the Kaplan-Meier method. The prognostic significance of PET parameters and other clinicopathological variables was assessed by Cox proportional hazards regression analysis. To evaluate and compare the predictive performance of PET parameters, time-dependent receiver operating characteristic (ROC) curve analysis was used., Results: In the multivariate analyses, volume-based parameters of PET (MTV and TLG) that were analyzed as continuous variables were significantly associated with an increased risk of recurrence (P = 0.001 for MTV, P < 0.001 for TLG) and death (P = 0.009 for MTV, P = 0.007 for TLG), after adjusting for age, sex, histology, tumor stage, and type of surgery. SUVmax analyzed as a continuous variable was not a significant prognostic factor for both DFS (P = 0.056) and OS (P = 0.525). In the time-dependent ROC curve analysis, the volume-based parameter of PET showed better predictive performance than SUVmax (P < 0.001)., Conclusions: The volume-based parameter of PET is an independent prognostic factor for survival in addition to pathological tumor-node-metastasis stage and a promising tool for better prediction of outcome in patients with early-stage NSCLC.

Background: The prognostic significance of volume-based metabolic parameters measured by (18)F-fluorodeoxyglucose positron emission tomography/CT ((18) F-FDG PET/CT) is not established. We evaluated the prognostic value of metabolic parameters in patients with squamous cell carcinoma (SCC) of the tonsil., Methods: We enrolled a total of 69 patients with SCC of the tonsil who underwent pretreatment (18)F-FDG PET/CT. We measured maximum standardized uptake value (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and asymmetry indices (of SUV(max), MTV, and TLG). The prognostic significance of these parameters and clinical variables was assessed by Cox proportional hazards regression analysis., Results: Multivariate analyses with adjustments for age, sex, and American Joint Committee on Cancer stage showed that only TLG (hazard ratio = 1.020, 95% confidence interval 1.003-1.037, p = .023) was an independent predictive factor associated with decreased overall survival., Conclusion: TLG is a significant independent metabolic prognostic factor for overall survival in patients with SCC of the tonsil., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: To evaluate the prognostic value of volume-based metabolic parameters measured with (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) in patients with clinically node-negative (cN0) oral tongue squamous cell carcinoma (OTSCC) as compared with other prognostic factors., Materials and Methods: In this study, we included a total of 57 patients who had been diagnosed with cN0 tongue cancer by radiologic, (18)F-FDG PET/CT, and physical examinations. The maximum standardized uptake value (SUV(max)), average SUV (SUV(avg)), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumors were measured with (18)F-FDG PET. The prognostic significances of these parameters and other clinical variables were assessed by Cox proportional hazards regression analysis., Results: In the univariate analysis, pathological node (pN) stage, American Joint Committee on Cancer (AJCC) stage, SUV(max), SUV(avg), MTV, and TLG were significant predictors for survival. On a multivariate analysis, pN stage (hazard ratio = 10.555, p = 0.049), AJCC stage (hazard ratio = 13.220, p = 0.045), and MTV (hazard ratio = 2.698, p = 0.033) were significant prognostic factors in cN0 OTSCC patients. The patients with MTV ≥ 7.78 cm(3) showed a worse prognosis than those with MTV < 7.78 cm(3) (p = 0.037)., Conclusion: The MTV of primary tumor as a volumetric parameter of (18)F-FDG PET, in addition to pN stage and AJCC stage, is an independent prognostic factor for survival in cN0 OTSCC.

Purpose: To investigate the effects of variable measurement methods on mean and maximum SUV ratios of 18F-FDG uptake in carotid arteries., Methods: 18F-FDG PET/CT images of 74 subjects with carotid plaque were analyzed for mean and maximum target-to-background ratio (TBR) of uptake. Agreement was analyzed between TBR scores obtained using different vessel coverage and slice skipping., Results: Mean TBR was increased by extending coverage from common carotid artery (CCA; 1.25) to carotid artery (CA; 1.33) and inclusion of ascending aorta (CA/AA; 1.34). Maximum TBR was increased from 1.47 to 1.54 and 1.61 by respective extensions. Both mean and maximum TBR were closely correlated between vessels. ICC and Kappa statistics revealed near perfect agreement between TBR obtained using every 2 or 3 segments and that without sipping. Bland-Altman plots showed bias by slice skipping to remain small, particularly for mean TBR. Finally, high correlations were displayed between mean and maximum TBR., Conclusions: Analysis of mean and maximum arterial 18F-FDG uptake in patients with carotid plaque is likely to benefit from extending coverage to segments above and below the CCA. The extra burden of measurement, in turn, can be lightened by skipping up to every 2 of 3 slices without compromising accuracy of results.

Purpose: Although the optimum treatment of primary central nervous system lymphoma (PCNSL) remains a challenge, there is increasing interest in methotrexate-based chemotherapy as an effective strategy. Here, we report evidence supporting the utility of methionine PET/CT for evaluating PCNSL disease extent and response to high-dose methotrexate therapy., Patients and Methods: Four patients newly diagnosed with diffuse large B-cell PCNSL underwent methionine PET/CT and MRI of the brain at baseline and again after completion of high-dose methotrexate combination chemotherapy. Three patients also received pretreatment FDG PET/CT, and the intervals between MRI and both PET/CTs were within 3 weeks. The results of methionine PET/CT were compared with MRI and clinical findings., Results: Pretreatment methionine PET/CT demonstrated clear demarcation of PCNSL tumors with high contrast in 3 patients and only faint uptake in the remaining patient, which also showed low FDG uptake. In 1 patient, methionine PET/CT displayed more tumor lesions than FDG PET/CT did. After high-dose methotrexate chemotherapy, methionine images displayed complete disappearance of abnormal uptake in all 4 patients. In 3 of the patients, posttreatment MRI and clinical follow-up corroborated findings of complete remission. In the remaining patient, MRI showed nonenhancing T2 hyperintensities in the periventricular white matter, for which the significance was inconclusive., Conclusions: Methionine PET/CT may provide clinically useful information complementary to MRI for monitoring the response to systemic chemotherapy in patients with PCNSL.

Objective: We compared the prognostic value of volume-based metabolic parameters determined using fluorine 18 (F) fluorodeoxyglucose (FDG) positron emission tomography (PET) (F-FDG PET) (with other prognostic parameters in uterine cervical cancer., Methods: The subjects were 73 female patients who had an initial diagnosis of uterine cervical cancer and who underwent F-FDG PET. Various metabolic or volume-based PET parameters including maximum and average standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) were measured in primary cervical tumors. Survival analysis for disease-free survival or progression-free survival was performed with a Kaplan-Meier method using PET parameters and other clinical variables. For determining independent prognostic factors, Cox regression analysis was performed., Results: Recurrence or disease progression occurred in 23 patients (31.5%). In univariate analysis, patient age (cutoff, 57 years, P < 0.05), International Federation of Gynecology and Obstetrics stage (P = 0.07), primary tumor size (cutoff, 6.7 cm; P < 0.05), lymph node status on PET (P < 0.005), treatment method (P < 0.01), metabolic tumor volume (cutoff, 82 cm; P = 0.001), and TLG (cutoff, 7600; P = 0.005) were significant predictors of recurrence or progression. In multivariate analysis, both lymph node status on PET (hazard ratio, 1.042 [negative vs intrapelvic metastasis only], 7.008 [negative vs extrapelvic metastasis]; P < 0.001) and TLG (cutoff, 7600; hazard ratio, 2.981; P < 0.05) were independent prognostic factors for predicting recurrence., Conclusions: In uterine cervical cancer, TLG, a volume-based metabolic parameter, and lymph node status on PET may be significant independent prognostic factors for event-free survival.

Purpose: To evaluate the feasibility of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)-guided conformal brachytherapy treatment planning in patients with cervical cancer., Methods and Materials: Pretreatment FDG-PET/CT was performed for 12 patients with cervical cancer. Brachytherapy simulation was performed after an external-beam radiation therapy median dose of 4140 cGy. Patients underwent FDG-PET/CT scans with placement of tandem and ovoid applicators. The gross tumor volume (GTV) was determined by adjusting the window and level to a reasonable value and outlining the edge of the enhancing area, which was done in consultation with a nuclear medicine physician. A standardized uptake value profile of the tumor margin was taken for each patient relative to the maximum uptake value of each tumor and analyzed. The plan was designed to deliver 400 cGy to point A (point A plan) or to cover the clinical target volume (CTV) (PET/CT plan)., Results: The median dose that encompassed 95% of the target volume (D95) of the CTV was 323.0 cGy for the point A plan vs 399.0 cGy for the PET/CT plan (P=.001). The maximum standardized uptake values (SUV(max)) of the tumors were reduced by a median of 57% (range, 13%-80%). All but 1 patient presented with discernable residual uptake within the tumors. The median value of the thresholds of the tumors contoured by simple visual analysis was 41% (range, 23%-71%)., Conclusions: In this study, the PET/CT plan was better than the conventional point A plan in terms of target coverage without increasing the dose to the normal tissue, making optimized 3-dimensional brachytherapy treatment planning possible. In comparison with the previously reported study with PET or CT alone, we found that visual target localization was facilitated by PET fusion on indeterminate CT masses. Further studies are needed to characterize the metabolic activity detected during radiation therapy for more reliable targeting., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the usefulness of histopathologic scoring for survival prediction in patients with solitary pulmonary nodular (SPN) lung adenocarcinomas and to correlate the histopathologic scoring with the results of computed tomography (CT) and fluorine 18 fluorodeoxyglucose positron emission tomography (PET)/CT., Materials and Methods: This retrospective study was institutional review board approved and the requirement for informed consent was waived. A total of 148 patients with SPN lung adenocarcinoma underwent PET/CT and CT. Correlations between histopathologic scores estimated by using two predominant histologic subtypes from each surgically resected specimen and the mass of the nodule at CT or maximum standardized uptake value (SUV(max)) at PET/CT were assessed. Disease-free survival (DFS) was estimated by using the Kaplan-Meier method, and the log-rank test was used to evaluate differences in each histopathologic subtype., Results: In 135 (91%) patients, tumors had a mixed subtype. The most frequently observed histologic subtypes, in decreasing order, were acinar (51%), lepidic (18%), solid (10%), and papillary (9%). DFS rates at 5 years were higher than 90% for the group of patients with nodules that showed the lepidic growth pattern, and 50% for patients with nodules that showed the micropapillary pattern. The pathologic score proved to be a significant predictor of DFS (P < .001). Both SUV(max) and the mass of the nodule were closely correlated with pathologic score., Conclusion: Pathologic scoring appears to help predict DFS in patients with SPN lung adenocarcinoma and shows close correlation with imaging biomarkers including the mass of the nodule at CT and SUV(max) at PET/CT., (© RSNA, 2012)

Objectives: To determine the positive reading criteria for malignant nodes when interpreting combined MRI and PET/CT images for preoperative nodal staging in non-small-cell lung cancer (NSCLC)., Methods: Forty-nine patients with biopsy-proven NSCLC underwent both PET/CT and thoracic MRI [diffusion weighted imaging (DWI)]. Each nodal station was evaluated for the presence of metastasis by applying either inclusive (positive if either one read positive) or exclusive (positive if both read positive) criteria in the combined interpretation of PET/CT and MRI. Nodal stage was confirmed pathologically. The combined diagnostic accuracy of PET/CT and MRI was determined on per-nodal station and per-patient bases and compared with that of PET/CT alone., Results: In 49 patients, 39 (19%) of 206 nodal stations harboured malignant cells. Out of 206 nodal stations, 186 (90%) had concordant readings, while the rest (10%) had discordant readings. Inclusive criteria of combined PET/CT and MRI helped increase sensitivity for detecting nodal metastasis (69%) compared with PET/CT alone (46%; P = 0.003), while specificity was not significantly decreased., Conclusion: Inclusive criteria in combined MRI and PET/CT readings help improve significantly the sensitivity for detecting nodal metastasis compared with PET/CT alone and may decrease unnecessary open thoracotomy. Key Points • Combined interpretation of MRI and PET/CT enhances the detection of nodal metastasis. • Inclusive criteria of combined MRI/PET/CT improved the sensitivity for detecting nodal metastasis. • Combined interpretation of MRI and PET/CT may reduce unnecessary open thoracotomies.

Rationale and Objectives: To evaluate the prognostic significance of maximum standardized uptake value (SUVmax) at (18)F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography in patients with stage IIIA non-small-cell lung cancer (NSCLC) who underwent surgical resection after neoadjuvant chemoradiotherapy, focused on the relationship between SUVmax values and tumor histology., Materials and Methods: We retrospectively evaluated the initial SUVmax of 205 patients (112 adenocarcinomas, 82 squamous cell carcinomas [SCCs], and 11 of other histology) with a stage IIIA NSCLC who underwent surgical resection after neoadjuvant chemoradiotherapy, and who were followed for up to 6 years. Clinical data, including histologic type, pathologic response, and treatment, were reviewed, and the relationship between the SUVmax and patient overall survival was examined., Results: Overall, the 2-year survival rate was 68%. Between the two histologic subtypes of adenocarcinoma and SCC, we noted significant differences in all variables of gender (male predominance in SCC), initial SUVmax (greater in SCC), pathologic response (more complete remission in SCC), and overall survival (better in SCC) (all P values, < .05). SUVmax remained as a sole independent factor for survival in multivariate analysis in whole series (SUVmax cutoff, 13; median survival, 3.0 years vs. 4.0 years; P = .016) and in adenocarcinomas (SUVmax cutoff, 11.5; median survival, 2.6 years vs. 3.6 years; P = .045), but not in SCCs., Conclusion: The initial SUVmax is a sole significant prognostic factor in patients with a surgically resected NSCLC after neoadjuvant chemoradiotherapy, particularly in patients with an adenocarcinoma., (Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.)

We report here on a rare case of primary AL hepatic amyloidosis associated with multiple myeloma in a 64-year-old woman. The patient was referred for evaluating her progressive jaundice and right upper quadrant pain. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) showed diffusely and markedly increased (18)F-FDG uptake in the liver. Although there have been several case studies showing positive (18)F-FDG uptake in pulmonary amyloidosis, to the best of our knowledge, the (18)F-FDG PET/CT findings of hepatic amyloidosis or primary hepatic amyloidosis associated with multiple myeloma have not been reported previously.

Aim: To date, no data are available on the use of PET/CT for preoperative staging of gastric cancer. We attempted to evaluate the value of PET/CT for preoperative staging of advanced gastric cancer, and to compare the use of PET/CT with contrast-enhanced CT (CECT)., Materials and Methods: We analyzed PET/CT of 78 patients with surgically proven advanced gastric cancer who had undergone preoperative CECT. Qualitative analysis was conducted by assessing the presence of primary tumors and metastases with PET/CT and CECT., Results: Among 71 patients who underwent a gastrectomy, 69 primary tumors (93%) were diagnosed by PET/CT, while 64 primary tumors (90%) were detected by CECT (p=0.55). For regional lymph node metastasis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET/CT vs. CECT were 41% vs. 25% (p=0.00019), 100% vs. 92% (p=0.31), 100% vs. 98% (p=0.46), 26% vs. 42% (p=0.14), and 51% vs. 72% (p=0.00089), respectively., Conclusion: Overall, PET/CT showed comparable diagnostic performance to CECT in diagnosing primary tumors and regional lymph node metastases, though PET/CT was inferior to CECT for the sensitivity and accuracy in diagnosing regional lymph node metastases. Nevertheless, PET/CT would be useful when CECT findings were equivocal due to its high positive predictability., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Acetylcholinesterase (AChE) has been an important cholinergic factor for the diagnosis of Alzheimer's disease (AD), because of reduced AChE activity in the postmortem brains of AD patients. We previously developed 5,7-dihydro-3-(2-(1-(2-[(18)F]fluorobenzyl)-4-piperidinyl)ethyl)-6H-pyrrolo(3,2,f)-1,2-benzisoxazol-6-one (2-[(18)F]fluoro-CP-118,954) for in vivo studies of AChE in mice. In the present study, we automated the synthesis of 2-[(18)F]fluoro-CP-118,954 for the routine use and evaluated the radioligand by microPET and ex vivo Cerenkov luminescence imaging of mouse AChE. 4-[(18)F]Fluoro-donepezil, another AChE inhibitor, was used for comparison. Automated syntheses of 2-[(18)F]fluoro-CP-118,954 and 4-[(18)F]fluoro-donepezil resulted in high radiochemical yields (25-33% and 30-40%) and high specific activity (27.1-35.4 and 29.7-37.3 GBq/μmol). Brain microPET images of two ICR mice injected with 2-[(18)F]fluoro-CP-118,954 demonstrated high uptake in the striatum (ROI analysis: 5.1 %ID/g for the first 30 min and 4.1 %ID/g for another 30 min), and a blocking study with injection of CP-118,954 into one of the mice at 30 min after radioligand injection led to complete blocking of radioligand uptake in the striatum (ROI analysis: 1.9 %ID/g), whereas (18)F-labeled donepezil did not show specific uptake in the striatum. In another set of experiments, the brain tissues (striatum, parietal cortex, frontal cortex and cerebellum) were excised after brain microPET/CT imaging of mouse injected with 2-[(18)F]fluoro-CP-118,954, and a high striatal uptake was also detected in ex vivo optical and microPET images (ROI analysis: 1.4 %ID/g) and in γ-counting data (2.1 %ID/g at 50 min post-injection) of the brain tissues. Taken together, these results demonstrated that 2-[(18)F]fluoro-CP-118,954 specifically binds to AChE in mouse brains., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: A new positron emission tomography (PET) detector signal processing method, the charge signal transmission approach, is proposed for the development of a hybrid PET-magnetic resonance imaging (MRI). A number of experiments were performed to demonstrate that the Geiger-mode avalanche photodiode (GAPD) charge output could be transmitted to a preamplifier using a long cable without degrading the PET signal performance., Methods: A PET module consisted of LYSO and a GAPD with a 4 x 4 array. The GAPD output was transmitted to the preamplifier through flexible flat cables. The effect of the cable length on the PET performance was examined using seven different lengths ranging from 10 to 300 cm outside and inside the 7 T animal MRI. Four parameters (rise time, fall time, amplitude, and area of the preamplifier output) were measured as a function of the cable length using a 10 GS/s oscilloscope and three parameters (photopeak position, energy resolution, and time resolution) were measured using a 100 MS/s DAQ unit. The effect of the cable length on the MR phantom images was investigated. In addition, the effect of the PET module configuration on its temperature stability was assessed by acquiring the energy and time spectra., Results: There were no significant changes in the PET module performance as a function of the cable length, both outside and inside MRI. The performance changes in energy information, such as the amplitude, area, photopeak position, and energy resolution, were <3% with cable lengths ranging from 10 to 300 cm and the change in the time resolution was <6%. There were no obvious artifacts or changes in the line profile in the MR phantom images. Moreover, no manifest changes in the photopeak position and coincidence counting rate were observed in the PET modules employing the charge signal transmission approach, whereas considerable degradation of the PET module performance was observed in the voltage signal transmission approach., Conclusions: This study demonstrated that it is feasible to design a hybrid PET-MRI using the charge signal transmission approach, which is expected to have more advantages than other approaches.

Background: To evaluate the importance of assessing volume-based parameter of (18)F-FDG PET/CT in patients with malignant pleural mesothelioma (MPM) for the prediction of response and patient outcome early in the course of treatment., Materials and Methods: Patients (n = 13; M:F = 9:4, mean age, 54 years) with histopathologically proven MPM, all of whom were scheduled to undergo curative extrapleural pneumonectomy (EPP) or palliative chemotherapy, were included in this study. They were evaluated using integrated (18)F-FDG PET/CT at baseline. Maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using PET/CT data. Relationships between tumor progression and PET parameters were statistically analyzed., Results: Of the 13 patients, 8 (62%) developed disease recurrence after surgery or tumor progression after chemotherapy (median follow-up, 329 days; range, 28-536 days). Between subgroups with and without tumor progression, significant differences were noted in MTV (P = 0.045). On ROC curve analysis, MTV (AUC = 0.850, 95% confidence interval [95% CI] 0.550-0.977) and TLG (AUC = 0.800, 95% CI 0.494-0.960) showed good predictive performance for tumor progression. Multivariate analysis adjusted for treatment modality showed that MTV (HR 1.003, P = 0.025) and TLG (HR 1.001, P = 0.031) were independent factors associated with tumor progression. Time to tumor progression was shorter in patients with a high volume-based parameter of PET than in those with a low value., Conclusions: Volume-based parameters of (18)F-FDG PET/CT have the potential to provide prognostic information in MPM patients who are receiving surgery or palliative chemotherapy.

Objective: We aimed to compare the incremental value of FDG PET/CT over CT for the assessment of mediastinal nodal status between patients with non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF) and those with NSCLC but without IPF., Materials and Methods: Forty-two patients with NSCLC and IPF (mean age, 66 years) were matched to 168 patients with NSCLC but without IPF (mean age, 65 years). Patients underwent surgical mediastinal nodal staging after both integrated PET/CT and contrast-enhanced CT scans had been obtained. Histopathologic nodal assessment served as the reference standard., Results: PET/CT had better specificity (91% [29/32 patients] vs 47% [15/32]; p = 0.0002) and accuracy (83% [35/42] vs 50% [21/42]; p = 0.001) than CT did in patients with IPF. In patients without IPF, PET/CT was better than CT alone with regard to sensitivity (62% [26/42] vs 40% [17/42]; p = 0.0067), specificity (96% [121/126] vs 84% [106/126]; p = 0.0002), and accuracy (88% [147/168] vs 73% [123/168]; p < 0.0001). Thus, the incremental accuracy of PET/CT, which was 33% (14/42) for patients with IPF and 14% (24/168) for patients without IPF (p = 0.0041), was mainly the result of improved specificity., Conclusion: PET/CT offers significantly increased accuracy versus CT in mediastinal nodal staging in patients with NSCLC and IPF compared with patients with NSCLC but without IPF, mainly because of improved specificity.

We studied the clinical relevance of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in patients with primary gastric lymphoma underwent positron emission tomography (PET)/ computed tomography (CT) scan. Forty-two patients with primary gastric lymphoma were analysed: 32 diffuse large B-cell lymphomas (DLBCL) and 10 extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas). The PET/CT scans were compared with clinical and pathologic features, and the results of CT and endoscopy. Nine patients were up-staged based on the results of their PET/CT scan compared to CT (seven DLBCLs, two MALT lymphomas) while six patients were down-staged by the PET/CT scan. The standard uptake value (SUV) was used as an indicator of a lesion with a high metabolic rate. The high SUVmax group, defined as an SUVmax >or= median value, was significantly associated with an advanced Lugano stage (p < 0.001). Three patients with DLBCL, who showed an initially high SUVmax, died of disease progression. Among 24 patients for whom follow-up PET/CT scan with endoscopy was performed, 11 patients with ulcerative or mucosal lesions showed residual (18)F-FDG uptake. All of these gastric lesions were grossly and pathologically benign lesions without evidence of lymphoma cells. In conclusion, PET/CT scan can be used in staging patients with primary gastric lymphoma; however, the residual (18)F-FDG uptake observed during follow-up should be interpreted cautiously and should be combined with endoscopy and multiple biopsies of the stomach., ((c) 2009 John Wiley & Sons, Ltd.)

Purpose: The aim of this study was to evaluate the prognostic value of metabolic tumor volume (MTV) measured by (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in patients with esophageal carcinoma., Methods: We retrospectively reviewed 151 patients with pathologically proven esophageal carcinoma (146 squamous cell carcinomas and 5 adenocarcinomas) who underwent pretreatment (18)F-FDG PET. MTV and maximum standardized uptake value (SUVmax) for the primary tumors were measured by (18)F-FDG PET. The prognostic significance of MTV, SUVmax, and other clinicopathological variables was assessed by Cox proportional hazards regression analysis. To further evaluate and compare the predictive performance of PET parameters, MTV and SUVmax, time-dependent receiver operating characteristic curve (ROC) analysis was used., Results: In the univariate analysis, age, American Joint Committee on Cancer (AJCC) stage, tumor-node-metastasis (TNM) factors, MTV, and SUVmax of primary tumor were significant predictors of survival. On multivariate analysis adjusted for age, sex, and treatment modality, independent predictive factors associated with decreased overall survival were T stage [hazard ratio (HR) 4.325, P = 0.006], M stage (HR 2.009, P = 0.007), and MTV (HR 1.013, P = 0.021). SUVmax was not a significant factor (HR 0.97, P = 0.061). On time-dependent ROC analysis, MTV showed good predictive performance for overall survival consistently better than SUVmax., Conclusion: MTV, a volumetric parameter of (18)F-FDG PET, is an important independent prognostic factor for survival and a better predictor of survival than SUVmax for the primary tumor in patients with esophageal carcinoma.

We aimed to evaluate prospectively the efficacy of positron emission tomography (PET)/computed tomography (CT) plus brain magnetic resonance imaging (MRI) for detecting extrathoracic metastases in lung adenocarcinoma. Metastatic evaluations were feasible for 442 consecutive patients (M:F=238:204; mean age, 54 yr) with a lung adenocarcinoma who underwent PET/CT (CT, without IV contrast medium injection) plus contrast-enhanced brain MRI. The presence of metastases in the brain was evaluated by assessing brain MRI or PET/CT, and in other organs by PET/CT. Diagnostic efficacies for metastasis detection with PET/CT plus brain MRI and with PET/CT only were calculated on a per-patient basis and compared from each other. Of 442 patients, 88 (20%, including 50 [11.3%] with brain metastasis) had metastasis. Regarding sensitivity of overall extrathoracic metastasis detection, a significant difference was found between PET/CT and PET/CT plus brain MRI (68% vs. 84%; P=0.03). As for brain metastasis detection sensitivity, brain MRI was significantly higher than PET/CT (88% vs. 24%; P<0.001). By adding MRI to PET/CT, brain metastases were detected in additional 32 (7% of 442 patients) patients. In lung adenocarcinoma patients, significant increase in sensitivity can be achieved for detecting extrathoracic metastases by adding dedicated brain MRI to PET/CT and thus enhancing brain metastasis detection.

Background: Performing a restaging work-up with magnetic resonance imaging (MRI) and (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography ((18)F-FDG PET/CT) can provide information about the effects that are related to preoperative concurrent chemoradiotherapy (CCRT). The purpose of the present study was to investigate the accuracy of MRI and (18)F-FDG PET/CT for restaging after preoperative CCRT for rectal cancer., Methods: Between April 2005 and February 2006, 30 patients with histologically proven rectal adenocarcinoma were included in this study. Pelvic MRI and (18)F-FDG PET/CT were performed to clinically restage the tumor after CCRT. The results of the pathologic staging were correlated with those of the MRI and (18)F-FDG PET/CT after CCRT. Two patients underwent transanal endoscopic microsurgery after CCRT, and they were excluded when the N category was evaluated., Results: The overall accuracy of MRI for the T category was 67% (kappa = 0.422, P = 0.003), whereas overstaging and understaging occurred in 30 and 3% of the patients, respectively. For the N category, accurate staging was noted in 75% (kappa = 0.410, P = 0.030) of all the patients, whereas 14% were overstaged and 11% were understaged. The overall accuracy rates for the T and N categories with performing (18)F-FDG PET/CT were 60% (kappa = 0.372, P = 0.004) and 71% (kappa = 0.097, P = 0.549), respectively. While MRI could not predict any patient who showed a pathologic complete response, (18)F-FDG PET/CT predicted three of the four patients who showed a pathologic complete response after preoperative CCRT. Furthermore, (18)F-FDG PET/CT identified distant metastases with an accuracy rate of 97%., Conclusions: For restaging patients with rectal cancer after preoperative CCRT, MRI is a useful diagnostic modality to predict both the T and N categories. (18)F-FDG PET/CT is helpful in predicting a pathologic complete response and in finding metastasis after preoperative CCRT.

We aimed to retrospectively compare CT, PET, and histopathologic (the extent of bronchioloalveolar carcinoma [BAC] components) findings of solitary pulmonary nodular (SPN) adenocarcinomas of the lung to determine their value as prognostic determinants. We reviewed CT and PET characteristics of tumors and pathologic specimens from 65 consecutive patients who underwent surgical resection for SPN adenocarcinomas. Nodule size and TDR (tumor shadow disappearance rate) were assessed from CT scans, and maximum standardized uptake value (SUVmax) of tumors was measured at PET. On pathologic examination, BAC, non-BAC, and central fibrous scar ratios were quantified. Prognosis was evaluated by noting disease recurrence during a minimum 12-month follow-up period after curative resection. The interrelationships between TDR, SUVmax, BAC, and non-BAC ratio were studied, and relationships between recurrence and various variables were analyzed. The median follow-up time was 33 months, and seven patients (11%) developed disease recurrence after surgical resection. TDR at CT and SUVmax at PET correlated well with pathologic BAC and non-BAC ratios. Between subgroups with and without recurrence, there were significant differences in SUVmax and BAC and non-BAC ratios. Based on univariate survival analyses, pathologic BAC and non-BAC ratios were risk factors significantly related to recurrence, but only high non-BAC ratio remained as an independent factor associated with recurrence in the multivariate analysis (hazard ratio [HR]=0.956, P=0.013). Among the factors examined, pathologic non-BAC ratio is the only independent risk factor for poor prognosis in patients with SPN adenocarcinomas.

We aimed to evaluate the CT, PET, and pathologic findings of solitary pulmonary nodular mucinous and nonmucinous bronchioloalveolar carcinomas (BACs). From August 2003 to March 2008, we saw 24 patients with solitary pulmonary nodular mucinous (n=6) or nonmucinous (n=18) BACs that were resected. CT and PET findings of the lesions were assessed in terms of size, solidity, morphologic characteristics, attenuation and maximum standardized uptake value (mSUV). All nonmucinous BACs appeared as a pure ground-glass opacity (GGO) nodule, whereas mucinous BACs appeared as solid (n=4) or part-solid (n=2) nodules. CT attenuation values were significantly higher for mucinous BACs (-21.0 HU+/-4.9) than for nonmucinous BACs (-491.8 HU+/-172.5) (P<.001). Mean mSUVs were 2.3+/-1.9 for mucinous BACs and 0.5+/-0.8 for nonmucinous BACs (P=.007), but mSUVs were not statistically different after size adjustment (r=0.371, P=.081). Mucinous BACs appear as solid or part-solid nodules at CT, whereas nonmucinous BACs present as pure GGO nodules. Both subtypes of tumors show scant FDG uptake at PET.

Purpose: In order to assess the diagnostic performance of Positron emission tomography/Computed tomography (PET/CT) for detecting recurrence in gastric cancer patients with clinical or radiologic suspicion of recurrence after surgical resection., Materials and Methods: Over a 4-year period, 105 post-operative patients with gastric cancer, who underwent PET/CT due to clinical or radiologic suspicion of recurrence during follow-up, were collected after confirming their PET/CT findings. The number and site of positive FDG uptake were retrospectively analyzed, and were correlated with the final diagnosis, by calculating the diagnostic values and assessing the causes of misdiagnosis., Results: Of all 105 patients, 75 patients were confirmed to have true recurrence with 108 recurrence sites. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for diagnosing true recurrence on a per-person basis were 75%, 77%, 89%, 55%, and 75%, respectively. On a per-lesion basis, 75 (69%) of 108 true recurrences showed positive FDG uptake, while 75 (89%) of 84 positive FDG uptake was confirmed to have true recurrence., Conclusion: PET/CT was relatively accurate in detecting recurrence in post-operative patients with gastric cancer. Moreover, PET/CT might be helpful in confirming the presence of recurrence particularly in patients who were highly suspicious of recurrence, because of its high positive predictability.

Objective: We aimed to compare the prognoses of patients with pathologically true negative (P-TN) N2 and PET/CT false negative (FN) results in stage T1 non-small cell lung cancer (NSCLC)., Materials and Methods: Our institutional review board approved this retrospective study with a waiver of informed consent. The study included 184 patients (124 men and 60 women; mean age, 59 years) with stage T1 NSCLC who underwent an integrated PET/CT and surgery. After estimating the efficacy of PET/CT for detecting N2 disease, we determined and compared disease-free survival (DFS) rates in three groups (P-TN [n = 161], PET/CT FN [n = 12], and PET/CT true positive [TP, n = 11]) using the Kaplan-Meier analysis and log-rank test., Results: Pathologic N2 disease was observed in 23 (12%) patients. PET/CT had an N2 disease detection sensitivity of 48% (11 of 23 patients), a specificity of 95% (153 of 161), and an accuracy of 89% (164 of 184). The 3-year DFS rate in the PET/CT FN group (31%, 95% confidence interval [CI]; 13.6-48.0%) was similar to that of the TP group (16%, 95% CI; 1.7-29.5%) (p = 0.649), but both groups had significantly shorter DFS rates than the P-TN group (77%, 95% CI; 72.0-81.2%) (p < 0.001)., Conclusion: The PET/CT shows a high specificity, but low sensitivity for detecting N2 disease in stage T1 NSCLC. Patients with PET/CT FN N2 disease have survival rates similar to PET/CT TP N2 disease patients, which are both substantially shorter than the survival rate of P-TN patients.

Background: Few articles have been published on imaging findings of marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue (BALT) of the lung. We present CT scan and 18F-fluorodeoxyglucose (FDG) PET scan findings of the disease., Methods: From March 1995 to February 2007, 21 pretreatment patients (male patients, 9; female patients, 12; age range, 35 to 76 years; mean [+/- SD] age, 54 +/- 10.4 years) were seen who had pathologic diagnoses of marginal zone B-cell lymphoma of BALT. After CT scans were reviewed searching for specific patterns and distribution of parenchymal lung lesions, patients were classified as having the following four different patterns: (1) single nodular or consolidative; (2) multiple nodular or areas of consolidation; (3) bronchiectasis and bronchiolitis; and (4) diffuse interstitial lung disease (DILD) patterns. In six patients, in whom PET/CT scanning was performed, the pattern and the extent of maximum standardized uptake values (mSUVs) of FDG uptake were described., Results: A single nodular or consolidative pattern was observed in 7 of 21 (33%) patients, multiple nodular or areas of consolidation were observed in 9 patients (43%), bronchiectasis and bronchiolitis were observed in 3 patients (14%), and DILD was observed in 2 patients (10%). On PET scans (n = 6), lesions showed heterogeneous FDG uptake in five patients and homogeneous uptake in one patient, with mSUVs ranging from 2.2 to 6.3 (mean mSUV, 4.2 +/- 1.48)., Conclusions: Marginal zone B-cell lymphomas of BALT manifest diverse patterns of lung abnormality on CT scans, but single or multiple nodules or areas of consolidation are the main patterns that occur in a majority (76%) of patients. Most lesions show heterogeneous but identifiable FDG uptake on PET scans.

Objective: The aim of this study was to assess the diagnostic efficacy of integrated PET/CT using fluorodeoxyglucose (FDG) for the differentiation of benign and metastatic adrenal gland lesions in patients with lung cancer and to compare the diagnostic efficacy with the use of PET alone., Materials and Methods: Sixty-one adrenal lesions (size range, 5-104 mm; mean size, 16 mm) were evaluated retrospectively in 42 lung cancer patients. Both PET images alone and integrated PET/CT images were assessed, respectively, at two-month intervals. PET findings were interpreted as positive if the FDG uptake of adrenal lesions was greater than or equal to that of the liver, and the PET/CT findings were interpreted as positive if an adrenal lesion show attenuation > 10 HU and showed increased FDG uptake. Final diagnoses of adrenal gland lesions were made at clinical follow-up (n = 52) or by a biopsy (n = 9) when available. The diagnostic accuracies of PET and PET/CT for the characterization of adrenal lesions were compared using the McNemar test., Results: Thirty-five (57%) of the 61 adrenal lesions were metastatic and the remaining 26 lesions were benign. For the depiction of adrenal gland metastasis, the sensitivity, specificity, and accuracy of PET were 74%, 73%, and 74%, respectively, whereas those of integrated PET/CT were 80%, 89%, and 84%, respectively (p values; 0.5, 0.125, and 0.031, respectively)., Conclusion: The use of integrated PET/CT is more accurate than the use of PET alone for differentiating benign and metastatic adrenal gland lesions in lung cancer patients.

Objective: The purpose of our study was to show the integrated 18F-FDG PET/CT findings of salivary gland type carcinomas of the lung., Conclusion: Salivary gland type carcinomas of the lung appear as airway tumors with variable CT morphologies and show different patterns and extents of FDG uptake on PET images according to their grades of differentiation.

Objective: The purpose of this study was to describe retrospectively integrated PET/CT findings on pulmonary neuroendocrine tumors and to correlate the findings with prognosis., Materials and Methods: Between May 2003 and February 2005, 37 consecutively enrolled patients (33 men and four women; mean age, 60 years) with histopathologically proven pulmonary neuroendocrine tumors underwent 18F-FDG PET/CT after enhanced standalone CT. CT was used to analyze the morphologic features of the tumors and PET to measure maximum standardized uptake value (SUV). Maximum SUVs of carcinoid tumors, large-cell neuroendocrine carcinomas (LCNECs), and small-cell lung carcinomas (SCLCs) were compared, and maximum SUV and tumor stage and prognosis were correlated., Results: Four (two typical and two atypical) of the seven carcinoid tumors had no FDG uptake or less than mediastinal uptake. The maximum SUVs of primary tumors, in increasing order, were significantly different for carcinoids (mean, 4.0; median, 3.4), LCNECs (mean, 12.0; median, 10.7), and SCLCs (mean, 11.6; median, 11.7) (p = 0.006, Kruskal-Wallis test). There was no significant correlation between maximum SUV of the primary tumor and the tumor stages of carcinoids, LCNECs, or SCLCs (p = 0.08, Jonckheere-Terpstra test; p = 0.768, Mann-Whitney test). Results of receiver operating characteristics analysis showed a maximum SUV greater than 13.7 suggested a poor survival period in cases of LCNEC and SCLC., Conclusion: The maximum SUVs of neuroendocrine tumors are significantly different for carcinoid tumors, LCNECs, and SCLCs, and a high maximum SUV suggests short survival of patients with LCNEC or SCLC.

Background: Integrated (18)fluorine fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) has shown somewhat variable sensitivity and specificity for mediastinal nodal staging in granulomatous disease endemic areas. The purpose of the study was to prospectively evaluate the efficacy of PET/CT for mediastinal nodal staging in nonsmall cell lung cancer (NSCLC) patients in a tuberculosis-endemic country., Methods: Prospective assessment of the diagnostic efficacy of integrated PET/CT for detecting mediastinal nodal metastasis was performed in 674 patients (M:F ratio = 502:172; mean age, 61 years) with NSCLC. Patients underwent an integrated PET/CT examination and subsequent surgical nodal staging (by mediastinoscopy only in 121 patients and by thoracotomy in 553). Nodes showing greater (18)F-FDG uptake than mediastinum at PET without benign calcification or high attenuation >70 household unit (HU) at unenhanced CT were regarded as being positive for malignancy. The histologic nodal assessment results were used as reference standards., Results: Of 2477 mediastinal nodal stations evaluated in 674 patients, 275 (11%) stations in 180 (27%) patients proved to be malignant. On a per-person basis, the overall sensitivity, specificity, and accuracy of PET/CT for mediastinal nodal staging were 61% (110 of 180), 96% (473 of 494), and 86% (583 of 674), respectively. On a per-nodal station basis, they were 46% (126 of 275), 98% (2154 of 2202), and 92% (2280 of 2477)., Conclusions: Integrated PET/CT provides high specificity and reasonably high accuracy, but somewhat low sensitivity for mediastinal nodal staging of NSCLCs. The high specificity is achieved at the expense of sensitivity by interpreting calcified nodes or nodes with high attenuation at CT, even with high FDG uptake at PET, as benign in a tuberculosis-endemic region.

Background: We investigated the accuracy of performing cervical nodal evaluation with using integrated (18)F-fluoro deoxyglucose positron emission tomography (PET)/CT for squamous cell carcinoma (SCC) of the head and neck as compared with using PET and contrast-enhanced CT (CECT) alone., Methods: The presence of metastatic lymphadenopathy in each cervical nodal group (level I-VI) and the nodal (N) classification of 47 patients with SCC of the head and neck were determined by using PET, CECT, and PET/CT, respectively, and the results were verified according to the histopathologic findings., Results: Among the 91 foci that had abnormal uptake on PET, the combined PET/CT images provided additional information over PET for the anatomical localization and lesion characterization of 18 sites (19.8%) in 17 patients (36.2%). PET/CT also showed the best results among the three imaging modalities for the sensitivity, specificity, and accuracy (91.8, 98.9, and 97.1%, respectively) for predicting metastatic nodes on a level-by-level analysis, and PET/CT had a higher accuracy (85.1%) for the pathologic nodal classification over the clinical examinations (68.1%) or PET (70.2%)., Conclusions: Combined PET/CT images are more accurate than the PET or CECT images alone for conducting cervical node evaluation in the patients suffering with head and neck SCC.

Objective: The purpose of our study was to compare the diagnostic efficacies of helical dynamic CT and integrated PET/CT for the prediction of mediastinal nodal metastasis in stage T1 non-small cell lung cancer (NSCLC)., Materials and Methods: One hundred forty-three patients with stage T1 NSCLC underwent both helical dynamic CT and integrated PET/CT followed by surgical nodal staging. In helical dynamic CT, patients were regarded to have stage N2 disease when a nodule showed a peak enhancement > or = 110 H or a net enhancement > or = 60 H. In integrated PET/CT, nodes were regarded as positive for malignancy when they showed > or = 3.5 in maximum standardized uptake value with a discrete margin and more 18F-FDG uptake than mediastinal structures. Sensitivities, specificities, and accuracies for mediastinal nodal metastasis detection were compared for helical dynamic CT and integrated PET/CT using the McNemar test., Results: Of the 143 patients, 34 (24%) had positive mediastinal nodes. The sensitivity, specificity, and accuracy for mediastinal nodal metastasis prediction on helical dynamic CT were 65% (22 of 34 patients), 89% (97 of 109), and 83% (119 of 143), respectively, whereas those on integrated PET/CT were 56% (19 of 34), 100% (109 of 109), and 90% (128 of 143). The p values were 0.664, < 0.001, and 0.015., Conclusion: In stage T1 NSCLC, contrast-enhanced helical dynamic CT better predicts, but not significantly so, mediastinal nodal metastasis than PET/CT, whereas PET/CT shows perfect specificity and higher accuracy than helical dynamic CT.