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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.)

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.

Introduction: Recently, a new lung adenocarcinoma classification scheme was published. The prognostic value of this new classification has not been elaborated together with the value of imaging biomarkers including computed tomography (CT) and positron emission tomography (PET)., Methods: We reviewed pathologic specimens and imaging characteristics of primary tumors from 723 consecutive patients who underwent surgical resection for lung adenocarcinoma. On pathology, the predominant histologic subtype and pattern group were quantified. Tumor-shadow disappearance ratio (TDR) on CT and maximum standardized uptake value (SUVmax) on PET were assessed. The relationships between those variables and survival (overall survival [OS] and disease-free survival) were analyzed by using Kaplan-Meier curves and Cox regression analyses., Results: The median follow-up period was 3.8 years. There were 137 patients (19%) with recurrence and 167 patients (23%) with metastasis after surgical resection. Among 723 patients, 35 patients (4.8%) had adenocarcinoma in situ, 34 patients (4.7%) had minimally invasive adenocarcinoma, 125 patients (17.3%) had lepidic predominant, 314 patients (43.4%) had acinar predominant, 65 patients (9.0%) had papillary predominant, 23 patients (3.2%) had micropapillary predominant, 113 patients (15.6%) had solid predominant, and 14 patients (1.9%) had variant adenocarcinomas. OS and disease-free survival rates were significantly different according to TDR on CT and SUVmax on PET, predominant subtypes, and pattern groups. On multivariate analysis, the SUVmax (p < 0.001), TDR (p = 0.038), and pattern group (p = 0.015) were independent predictors of OS., Conclusions: TDR on CT, SUVmax on PET, and the new histologic classification schemes appear to be promising parameters for the prognostic stratification of patients with lung adenocarcinomas, allowing for the triage of patients who necessitate further staging workup and adjuvant therapy.

18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is an evolving tool in the field of oncology. 18F-fluorodeoxyglucose, however, is not a specific tool for malignant tumor that it may also accumulate in benign processes. To avoid false-positive interpretation of 18F-FDG-PET/computed tomography (CT), having knowledge of the potential pitfalls is important.The authors present a case of a patient with a lung mass who underwent fluoroscopy-guided transthoracic lung biopsy followed by 18F-FDG-PET/CT scan with a 4-hour interval between biopsy and scanning. Abnormally increased FDG uptake in the mass and pleural effusion was detected. Pathologic examination of the specimen, however, revealed only fibrous tissues with chronic inflammatory cells. On performing CT imaging, 1 month later, the mass and effusion had spontaneously resolved without treatment.Our findings suggest that PET/CT performed immediately following invasive procedures can result in false-positive results and thus mislead diagnosis. Therefore, the interval and order, in which PET/CT and invasive procedures are performed, should be carefully considered in oncologic work-up.

Objective: We evaluated the prognostic impact of volume-based assessment by pretreatment (18)F-FDG PET/CT in patients who had clinical stage IIIA-N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgical resection., Materials and Methods: We reviewed 161 consecutive patients who had stage IIIA-N2 NSCLC treated with neoadjuvant CCRT followed by surgery. In all cases, N2 disease was pathologically confirmed by mediastinoscopic biopsy, endobronchial ultrasound-guided transbronchial needle aspiration, or video-assisted thoracoscopic surgery. We measured the total metabolic tumor volume (total MTV) and the maximum standardized uptake value (SUVmax), including a primary tumor and metastatic nodes on the pretreatment scan. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. The association of PET parameters with OS and DFS was determined by univariable and multivariable analyses performed using the Cox regression model., Results: A higher total MTV was significantly associated with poor DFS (hazard ratio [HR], 1.82; p = 0.036) and OS (HR = 2.97; p = 0.012) in the multivariable analysis. In contrast, a higher SUVmax was not significantly associated with poor DFS and OS. Patients with a high total MTV (> 22 cm(3)) had a median survival time that was significantly shorter than that of patients with a low total MTV (median DFS, 11.3 vs 42.0 months, respectively [p < 0.001]; median OS, 38.3 months vs not reached [p < 0.001]). Kaplan-Meier curves showed significant differences on the basis of total MTV in patients with or without mediastinal downstaging after CCRT. Patients with a high total MTV had significantly worse DFS when they had post-neoadjuvant pathologic (yp) stage 0-II disease (p = 0.020) or yp stage III disease (p = 0.036). Higher total MTV was also associated with worse OS in patients with yp stage 0-II disease (p = 0.013) or yp stage III disease (p = 0.007)., Conclusion: A higher pretreatment total MTV is associated with worse outcome, independent of yp stage, in patients with stage IIIA-N2 NSCLC treated with neoadjuvant CCRT followed by surgery.

Objective: The utility of (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scanning and brain magnetic resonance imaging (MRI) as a staging workup for lung adenocarcinoma manifesting as pure ground glass opacity (GGO) is unknown. The purpose of this study was to determine the utility of these 2 tests for preoperative staging of pure GGO nodular lung adenocarcinoma., Methods: The study included 164 patients (male:female, 73:91; mean age, 62 years) with pure GGO nodular lung adenocarcinoma who underwent PET/CT (in 136 patients) and/or brain MRI (in 109 patients) before surgery. Pathologic N staging and dedicated standard imaging or follow-up imaging findings for M staging were used as reference standards. The median follow-up time was 47.9 months., Results: On PET/CT scan, abnormal FDG uptake of lymph nodes was found in 2 of 136 patients (1.5%); both were negative on final pathology. Abnormal FDG uptake of the liver was detected in 1 patient, which was also confirmed to be negative by dedicated abdominal CT. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT in detecting metastases were not applicable, 98% (95% confidence interval [CI], 94%-100%), 0% (95% CI, 0%-71%), 100% (95% CI, 97%-100%), and 98% (95% CI, 94%-100%), respectively. No brain metastasis was found in preoperative brain MRI of 109 patients. Of 109 patients, 1 (0.9%) developed brain metastasis 30 months after surgical resection., Conclusions: PET/CT and brain MRI is not necessary in the staging of pure GGO nodular lung adenocarcinoma., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

We report a rare case of primary pulmonary low-grade angiosarcoma on dynamic contrast-enhanced CT and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging. A 38-year-old, asymptomatic woman was hospitalized because of an abnormality on chest radiography. A dynamic contrast-enhanced chest CT showed a 1.2 cm-sized irregular-margined nodule with strong and persistent enhancement in the right lower lobe. The lesion had low metabolic activity on an (18)F-FDG PET/CT scan. The patient underwent a wedge resection for the lesion, and pathology revealed a primary pulmonary low-grade angiosarcoma.

Objective: The maximum standardized uptake value (SUVmax) of pulmonary mucoepidermoid carcinoma (PMEC) in fluorine-18fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) was evaluated as a preoperative predictor of pathologic grade and survival rate., Materials and Methods: Twenty-three patients who underwent preoperative PET/CT and complete resection for PMEC were enrolled. The optimal cut-off SUVmax for tumor grade was calculated as 6.5 by receiver operating characteristic curve. The patients were divided into a high SUV group (n = 7) and a low SUV group (n = 16). Clinicopathologic features were compared between the groups by χ(2) test and overall survival was determined by Kaplan-Meier analysis., Results: The mean SUVmax was 15.4 ± 11.5 in the high SUV group and 3.9 ± 1.3 in the low SUV group. All patients except one from the low SUV group had low grade tumors and all had no nodal metastasis. The sensitivity and specificity of SUVmax from PET/CT for predicting tumor grade was 85.7% and 93.8%, respectively. During the follow-up period (mean, 48.6 ± 38.7 months), four patients from the high SUV group experienced cancer recurrence, and one died of cancer. In contrast, none of the low SUV group had recurrence or mortality. Five-year overall survival rate was significantly higher in the low SUV group (100% vs. 71.4%, p = 0.031)., Conclusion: Pulmonary mucoepidermoid carcinoma patients with high SUVmax in PET/CT had higher tumor grade, more frequent lymph node metastasis and worse long-term outcome. Therefore, PMEC patients with high uptake on PET/CT imaging might require aggressive mediastinal lymph node dissection and adjuvant therapies.

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.)

Purpose: To evaluate the prognostic value of a volume-based metabolic tumor response to neoadjuvant chemotherapy in patients with locally advanced breast cancer., Materials and Methods: This study was approved by the institutional review board, with waivers of informed consent. One hundred sixty-seven patients (mean age, 44 years; range, 22-68 years) with clinical stage II or III breast cancer who underwent fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography scans at baseline and after completion of neoadjuvant chemotherapy between July 2006 and June 2013 were selected. The association between the metabolic response parameters and the disease-free survival was assessed by using a Cox proportional hazards regression model and time-dependent receiver operating characteristic curve analysis. Metabolic response parameters included the maximum standardized uptake value (SUVmax), the total metabolic tumor volume (MTVtotal), and the relative decrease in SUVmax and MTVtotal., Results: In the Cox model, posttreatment SUVmax (P = .029) and MTVtotal (P = .028) and relative decreases in SUVmax (P = .032) and MTVtotal (P = .005) after neoadjuvant chemotherapy were significantly associated with disease-free survival after adjusting for pretreatment clinical stage, yp stage, and tumor subtype. In the time-dependent receiver operating characteristic curve analysis, MTVtotal after neoadjuvant chemotherapy had the highest association with outcome compared with the other parameters (P < .001). MTVtotal of up to 0.2 cm(3) after neoadjuvant chemotherapy was significantly associated with a favorable outcome in patients who did not achieve pathologic complete response after neoadjuvant chemotherapy., Conclusion: The volume-based metabolic tumor response to neoadjuvant chemotherapy is associated with an increased risk of recurrence, regardless of tumor subtype and pathologic tumor response., (© RSNA, 2014.)

Aim: Since positron emission tomography/computed tomography (PET/CT) has been introduced, many incidental findings have been identified. The aim of this study was to assess the clinical significance of incidental findings on PET/CT in patients with gastric cancer., Methods: A total of 421 patients with gastric cancer underwent PET/CT for initial staging. Incidental findings on PET/CT were classified into five categories according to clinical significance--normal variant, benign, probably benign, probably malignant, and definitely malignant. We obtained information regarding follow-up examinations, additional visits, final diagnosis of incidental findings and short-term medical costs for further evaluation., Results: Eight hundred eighty-two incidental findings were detected in 386 (91.7%) patients. Of 274 incidental findings classified as probably benign, probably malignant or definitely malignant, 130 required one or more additional investigations. Finally, 12 (9.2%) were proved to be associated with second primary malignancy or metastasis of gastric cancer. One hundred twenty-nine additional outpatient visits and 10 additional hospitalizations were needed for evaluating the incidental findings. The treatment strategy for gastric cancer was changed in one patient. The estimated cost of additional investigations was $US283 (95% CI: $US248-$US311) per patient., Conclusion: Incidental findings on PET/CT were common. Although the incidental findings were suspicious of malignancy, most were benign with high costs for additional investigations., (© 2015 Wiley Publishing Asia Pty Ltd.)

This study aimed to evaluate the prognostic significance and predictive performance of volume-based parameter of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in biliary tract cancer (BTC). Of the 268 patients who were enrolled onto phase III gemcitabine/oxaliplatin (GEMOX) versus GEMOX/erlotinib trial, a total of 48 patients had pretreatment (18)F-FDG PET/CT available for analysis. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis for the primary tumor were measured. The prognostic significance of these parameters and clinicopathological variables was assessed by Cox proportional hazards regression analysis. A cutoff of 98.8 ml for the MTVliver was the best discriminative value for predicting overall survival (>9 months). Multivariate analyses with adjustments for age, performance status, and disease status showed that only MTVliver was an independent prognostic factor associated with overall survival (HR 2.149, 95 % CI 1.124-4.109, P = 0.021). SUVmax did not show any correlation with overall survival. For patients in the high-MTVMBP group, overall survival was longer in the chemotherapy plus erlotinib group than in the chemotherapy-alone group [median 8.3 months (5.5-11.1) vs. 4.0 months (0.0-8.0); P = 0.048]. MTV may be considered as a significant independent metabolic prognostic factor for overall survival in patients with BTC and predictive marker for the selection of patients for the addition of erlotinib to first-line chemotherapy.

Objectives: To investigate the relationship between volume-based PET parameters and prognosis in patients with soft tissue sarcoma (STS)., Methods: We retrospectively reviewed 55 patients with pathologically proven STS who underwent pretreatment with (18) F-Fluorodeoxyglucose ((18)F-FDG) PET/CT. The maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary tumors were measured using a threshold SUV as liver activity for determining the boundary of tumors. Univariate and multivariate survival analyses for overall survival were performed according to the metabolic parameters and other clinical variables., Results: Cancer-related death occurred in 19 of 55 patients (35 %) during the follow-up period (29 ± 23 months). On univariate analysis, AJCC stage (stage IV vs. I-III, hazard ratio (HR) = 2.837, p = 0.028), necrosis (G2 vs. G0-G1, HR = 3.890, p = 0.004), SUVmax (1 unit - increase, HR = 1.146, p = 0.008), SUVavg (1 unit - increase, HR = 1.469, p = 0.032) and treatment modality (non-surgical therapy vs. surgery, HR = 4.467, p = 0.002) were significant predictors for overall survival. On multivariate analyses, SUVmax (HR = 1.274, p = 0.015), treatment modality (HR = 3.353, p = 0.019) and necrosis (HR = 5.985, p = 0.006) were identified as significant independent prognostic factors associated with decreased overall survival., Conclusions: The SUVmax of the primary tumor is a significant independent metabolic prognostic factor for overall survival in patients with STS. Volume-based PET parameters may not add prognostic information outside of the SUVmax.

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.

Objective: The purpose of our study was to demonstrate metabolic patterns on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in patients with adhesive capsulitis (AC)., Methods: We retrospectively reviewed (18)F-FDG PET/CT performed on 22 shoulders of 21 patients diagnosed with AC: 2 shoulders with stage I, 14 with stage II, and 6 with stage III. A clinical diagnosis of AC was retrospectively made based on clinical examination, clinical course, and imaging. The pattern of radiotracer uptake was analyzed. Standardized uptake values in rotator interval (RI), anterior joint capsule (AJC), axillary recess (AR), and greater tuberosity were measured and compared to those of the contralateral side and the control group consisting of 40 shoulders in 20 subjects without shoulder pain., Results: Four patterns of uptake were noted: (1) glenoid type I (n = 16), with uptake in RI, AJC, and AR; (2) glenoid type II (n = 2),with uptake in AJC and AR; (3) glenoid type III (n = 2), with uptake in RI and AJC; (4) focal type (n = 2), with uptake in RI or AR. Affected side SUVmax for RI, AJC, and AR was significantly higher compared with the unaffected side and the control group. Two shoulders with stage I AC had patterns similar to the ones with stage II or III., Conclusion: Specific patterns of (18)F-FDG uptake with dominant uptake in RI, AJC, or AR may be related to AC.

Purpose: We evaluated the prognostic impact of volume-based assessment by (18)F-FDG PET/CT in patients with stage III non-small-cell lung cancer (NSCLC)., Methods: We reviewed 194 consecutive patients with stage IIIA NSCLC treated with surgical resection (surgical group) and 115 patients treated with nonsurgical therapy (nonsurgical group: 50 stage IIIA, 65 stage IIIB). Metabolic tumour volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) of primary tumours were measured using pretreatment (18)F-FDG PET/CT. Overall survival was assessed using the Kaplan-Meier method. The prognostic significance of PET parameters and other clinical variables was assessed using Cox proportional hazards regression analyses. To evaluate and compare the predictive performance of PET parameters, time-dependent receiver operating characteristic (ROC) curve analysis was used., Results: In the Cox proportional hazards models, MTV (HR=1.27 for a doubling of MTV, P=0.008) and TLG (HR=1.22 for a doubling of TLG, P=0.035) were significantly associated with an increased risk of death after adjusting for age, gender, histological cell type, T stage, N stage, and treatment variables in the surgical group. SUVmax was not a significant prognostic factor in either the surgical or nonsurgical group. In the time-dependent ROC curve analysis, volume-based PET parameters predicted survival better than SUVmax., Conclusion: The volume-based PET parameters (MTV and TLG) are significant prognostic factors for survival independent of tumour stage and better prognostic imaging biomarkers than SUVmax in patients with stage IIIA NSCLC after surgical resection.

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.)

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.)

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.

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.

Purpose: Among patients with advanced non-small cell lung cancer (NSCLC), identification of a subgroup of patients for immediate maintenance treatment after first-line chemotherapy has great importance in improving survival. The purpose of this study was to investigate whether the metabolic responses evaluated by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) may be a potential screening tool for identifying patients with early disease progression who may benefit from immediate maintenance treatment., Methods: A total of 52 patients with advanced NSCLC (36 men and 16 women, mean age 57.2 ± 10.6 years) who underwent baseline and follow-up (18)F-FDG PET/CT after four cycles of first-line chemotherapy were enrolled. Maximum standardized uptake value (SUV(max)), SUV(peak), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the tumour lesions were measured and percentage decrease of the parameters was calculated. The prognostic significance of percentage decrease of these parameters and other clinical variables related to progression-free survival (PFS) and overall survival (OS) were assessed by Cox proportional hazards regression analysis. Receiver-operating characteristic (ROC) curve analysis was used to define the optimal cut-off value of percentage decrease of the parameters that could distinguish between early (PFS < 6 months) and late (PFS ≥ 6 months) disease progression groups., Results: Multivariate analysis showed that percentage decrease of TLG [hazard ratio per 10% decrease = 1.030, 95% confidence interval (CI) = 1.012-1.048, p = 0.001) was a significant predictor of PFS and OS. ROC curves identified a 50.0% decrease in TLG as the optimal cut-off value to distinguish disease progression groups. Positive and negative predictive values of the optimal TLG value for selecting patients with late disease progression were 36.4 and 100.0%, respectively., Conclusion: The percentage decrease in TLG of measurable tumour lesions may be a potential parameter to appropriately identify a subgroup of patients for immediate maintenance treatment after first-line chemotherapy in patients with advanced NSCLC.

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.)

Accurate prediction of cancer prognosis before the start of treatment is important since these predictions often affect the choice of treatment. Prognosis is usually based on anatomical staging and other clinical factors. However, the conventional system is not sufficient to accurately and reliably determine prognosis. Metabolic parameters measured by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) have the potential to provide valuable information regarding prognosis and treatment response evaluation in cancer patients. Among these parameters, volume-based PET parameters such as metabolic tumor volume and total lesion glycolysis are especially promising. However, the measurement of these parameters is significantly affected by the imaging methodology and specific image characteristics, and a standard method for these parameters has not been established. This review introduces volume-based PET parameters as potential prognostic indicators, and highlights methodological considerations for measurement, potential implications, and prospects for further studies.

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.

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: 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.

Taking a step forward from the IPI, attention is focused on the role of 18F-FDG PET/CT as a tool for guidance in risk stratification in patients with aggressive non-Hodgkin's lymphoma (NHL). Here, we analyzed the predictive value of various PET/CT parameters in patients with DLBCL. Particularly, we were interested in patients with an IPI score of 1, 2, or 3, whose prognosis are confusing. Between Jul 2008 and Feb 2010, a total of 100 patients (including 57 patients with an IPI score of 1-3) who were treated with R-CHOP for DLBCL, and had assessable PET/CT parameters were analyzed in this study. Absolute value of SUVmax, SUVsum(sum of SUVmax) and TLGsum(SUVmean x Volumemeta) from baseline and interim PET/CT, and ΔSUVsum, ΔSUVmax, and ΔTLGsum between baseline and interim PET/CT were selected as PET/CT parameters. The median number of R-CHOP cycles was 6, and interim PET/CT was performed after 2 or 3 cycles. None of the parameters which showed percentile change between initial and interim PET/CT were associated with prognosis. Instead, absolute value of SUVsum from baseline PET/CT, and SUVmax and SUVsum from interim PET/CT were significantly relevant to PFS in all patients, and in patients with an IPI score of 1–3.

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.)

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.

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.

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.)

Background: The major concerns in the surgical treatment of extensive or recurrent thyroid cancer include the difficulty of precise intraoperative and real-time tumor localization, the possibility of missing small metastatic lymph nodes during the operation, the need for reoperation due to recurrence, and complications. The usefulness and feasibility of an intraoperative PET probe have been reported for many other cancers; however, a standard, radioguided, operative protocol using a PET probe in thyroid cancer has not been established. The purpose of the current study was to evaluate the feasibility of an intraoperative PET probe with respect to precise tumor localization, verification of complete resection, and a decrease in unnecessary reoperations and complications., Methods: This was a prospective, controlled study. Inclusion criteria were thyroid cancer requiring a total thyroidectomy with a modified radical neck dissection (MRND) and recurrent thyroid cancer after thyroid surgery. The types of procedures included total thyroidectomy with MRND, selective neck dissection (SND), and excision of recurrent thyroid masses. The PET probe NodeSeeker(®) is a high-energy gamma probe seeking 511 keV photons. Operative exploration was carried out between 2 and 6 h after injection of (18)F-FDG. The surgeon calculated the target-to-background ratio (T/B ratio) by checking the 10-sec accumulated count using the PET probe. We performed a re-exploration if the T/B ratio was >1.3 in the operative bed., Results: Twelve patients underwent PET probe-guided operation. SNDs, mass excisions, total thyroidectomy with MRND, and MRND were performed on 7, 4, and 1 patient, respectively. All tumors were localized by the PET probe precisely in real time, and the lesions not observed on preoperative PET were detected by the PET probe in 7 patients. Furthermore, additional lymph nodes that were not identified on preoperative ultrasonography were detected in 1 patient. The mean T/B ratio of thyroid carcinoma was 1.51 ± 0.53 (range, 1.17-4.03) and the postoperative serum thyroglobulin off thyroid hormone was <2.0 ng/ml., Conclusion: Radioguided surgery using an intraoperative PET probe in thyroid cancer appears to be a useful method for real-time tumor localization, verification of complete excision, and minimization of the possibility of residual cancer. Therefore, an intraoperative PET probe in thyroid cancer may decrease unnecessary reoperations and complications due to persistent disease., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Introduction: The objectives of this study were (1) to assess the results of mediastinoscopy and mediastinal lymphadenectomy and (2) to compare outcomes of surgical treatment with or without neoadjuvant therapy in patients with non-small cell lung cancer who are N2 negative on integrated positron emission tomography and computed tomography (PET/CT)., Methods: This was a retrospective, single-institution review of patients with non-small cell lung cancer who were N2 negative on CT and PET/CT. All patients underwent mediastinoscopy; if N2 positive, patients underwent neoadjuvant therapy followed by pulmonary resection, and if N2 negative, patients underwent pulmonary resection with mediastinal lymphadenectomy., Results: Between 2003 and 2007, there were 750 patients (547 men). Of these, 51 patients were N2 positive at mediastinoscopy and then underwent neoadjuvant therapy (mediastinoscopy N2 group), and 699 were N2 negative at mediastinoscopy and then underwent mediastinal lymphadenectomy. Mediastinal lymphadenectomy revealed that 635 had N0 or N1 disease (N2-negative group), and 64 had N2 disease (surgery N2 group). Overall 5-year survival was 73% for the N2-negative group, 44% for the surgery N2 group, and 47% for the mediastinoscopy N2 group. Disease-free 5-year survival was 59% for the N2-negative group, 27% for the surgery N2 group, and 29% for the mediastinoscopy N2 group., Conclusions: We found that there were no significant differences in overall and disease-free survivals between the surgery N2 group and the mediastinoscopy N2 group. The benefit of neoadjuvant therapy in patients with PET/CT-negative but mediastinoscopy-positive N2 disease should be confirmed by randomized studies.

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.

Tumor localization is difficult in patients with medullary thyroid carcinoma (MTC) that have persistent hypercalcitoninemia after thyroidectomy. In this study, the (11)C-methionine positron emission tomography/computed tomography (PET/CT) was compared with the (18)F-FDG PET/CT for diagnostic sensitivity in detecting residual or metastatic disease. (11)C-methionine PET/CT and (18)F-FDG PET/CT were performed on 16 consecutive patients with MTC that had persistent hypercalcitoninemia after surgery in this prospective, single-center study. Patient- and lesion-based analyses were performed using a composite reference standard which was the sum of the lesions confirmed by all combined modalities, including neck ultrasonography (US) with or without fine needle aspiration cytology, CT, bone scan, magnetic resonance imaging (MRI), and surgery. By patient-based analysis, the sensitivities of (11)C-methionine PET/CT and (18)F-FDG PET/CT were both 63%. By lesion-based analysis, the sensitivity of (11)C-methionine PET/CT was similar to (18)F-FDG PET/CT (73% vs. 80%). Excluding hepatic lesions, which could not be detected because of physiological uptake of methionine by the liver, the sensitivity of (11)C-methionine PET/CT was better than (18)F-FDG PET/CT especially for detecting cervical lymph node lesions; however, it was not superior to US. All patients with serum calcitonin levels ≥370 pg/mL showed uptake by (11)C-methionine PET/CT and (18)F-FDG PET/CT. This preliminary data showed that despite its similar sensitivity to (18)F-FDG PET/CT for detecting residual or metastatic MTC, (11)C-methionine PET/CT provided minimal additional information compared to combined (18)F-FDG PET/CT and neck US.

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.

Introduction: The intensity of 18F-fluorodeoxyglucose (18F-FDG) uptake in positron emission tomography could be of prognostic significance for patients with non-small cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the prognostic value of the FDG uptake in patients with resected pathologic stage I NSCLC according to histologic types of the tumors., Methods: For each patient, a maximum standardized uptake value (SUVmax) and a partial volume corrected (PVC) SUVmax were calculated for the primary lesion on positron emission tomography. To find optimal cutoff values for cancer recurrences, receiver operating characteristic curves were used., Results: Among 145 study patients, the mean values of SUVmax were 7.7 in those with adenocarcinoma (n = 70) and 16.0 in those with other histologies (n = 75; p < 0.001). Furthermore, the optimal cutoff values of SUVmax to predict cancer recurrences were identified as 5.2 in patients with adenocarcinoma and 13.8 in those with other histologies. In whole patients with pathologic stage I NSCLC, SUVmax (p = 0.025), PVC SUVmax (p = 0.014), tumor size (p = 0.048), and weight loss (p = 0.041) were significantly associated with disease-free survival (DFS). Moreover, PVC SUVmax (p = 0.034) and SUVmax (p = 0.012) were significantly associated with DFS in the multivariate analyses., Conclusions: The intensity of FDG uptake for the primary tumor was an independent prognostic factor for DFS in whole patients with pathologic stage I NSCLC. However, caution is needed for the interpretation of optimal cutoff values of SUVmax according to tumor histologies.

Background: To investigate the correlation between pretreatment metabolic tumor volume (MTV) as determined by [(18)F]-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and occult metastasis (OM) in oral squamous cell carcinoma (OSCC) of the tongue., Methods: Forty-three clinically node-negative (cN0) OSCC patients, diagnosed by preoperative workups (biopsy, physical examination, CT, and PET/CT) were enrolled. All patients had undergone primary tumor resections and elective neck dissections. MTVs were measured for tumors showing standardized uptake value (SUV) of >2.5 by an automated contouring program. Pretreatment variables (age, sex, clinical T stage, maximal SUV [SUV(max)] and MTV) and posttreatment variables (pathologic T stage, depth of invasion, lymphovascular invasion, pathologic tumor volume, and histological differentiation) were analyzed to identify their correlation with OM., Results: Twelve (27.9%) of 43 patients were found to have OM in pathologic specimen of neck dissections. A cutoff of 6.0 ml for the MTV was determined to be the most discriminative value for predicting OM. By univariate analysis, the patients with an MTV of >6.0 ml had significantly higher number of occult metastases than those with an MTV of

Purpose: This study aimed to investigate whether metabolic tumor volume (MTV) measured from [(18)F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) predicts short-term outcome to radiotherapy with or without chemotherapy and disease-free survival (DFS) in patients with pharyngeal cancers., Experimental Design: The MTVs of primary sites with or without neck nodes were measured in 82 patients. Short-term outcome was assessed using the treatment response evaluation by the Response Evaluation Criteria in Solid Tumors and recurrence events during follow-up (complete response/no recurrence or residual disease/recurrence)., Results: A total of 64 patients had complete response/no recurrence as of the last follow-up. A cutoff of 40 mL for the MTV was the best discriminative value for predicting treatment response. By univariate analyses, patients with MTV > 40 mL showed a significantly lower number of complete response/no recurrence than did patients with MTV < or =40 mL [68.2% versus 87.8%; hazard ratio (HR), 3.34; 95% confidence interval (95% CI), 1.09-10.08; P = 0.03], as is the same in tumor-node-metastasis stage (87.5% for I-II versus 90% for III versus 63.8% for IV; P = 0.02). However, MTV was only a significant predictor of short-term outcome by multivariate analyses (HR, 4.09; 95% CI, 1.02-16.43; P = 0.04). MTV > 40 mL indicated a significantly worse DFS than MTV < or =40 mL (HR, 3.42; 95% CI, 1.04-11.26;P = 0.04). The standardized uptake value for the primary tumor did not show any correlation with treatment outcome or DFS., Conclusion: MTV has a potential value in predicting short-term outcome and DFS in patients with pharyngeal cancers.

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.

Introduction: Sinonasal inverted papilloma (IP) is known for high rate of associated malignancy. The purpose of this study was to identify (18)F-FDG PET/CT findings of sinonasal IPs. We also tried to compare the PET/CT findings with the MR imaging findings., Methods: We retrospectively reviewed PET/CT and MR images of eight patients with sinonasal IP with (n = 6) or without (n = 2) coexistent squamous cell carcinoma (SCC). Particular attention was paid to correlate the PET/CT findings with the MR imaging findings in terms of area distribution of standard uptake values (SUVs) and a convoluted cerebriform pattern (CCP)., Results: In two benign IPs, the maximum SUVs measured 8.2 and 7.8, respectively (mean, 8.0). In both tumors, MR images demonstrated a diffuse CCP. In six IPs with coexistent SCC, the maximum SUVs ranged from 13.3 to 31.9 (mean +/- SD, 20.2 +/- 6.6). In these tumors, MR images demonstrated a diffuse CCP in two, a partial CCP in three, and no CCP in one. A wide discrepancy was noted between MR imaging and PET/CT in terms of area distribution of a CCP and SUVs., Conclusion: In sinonasal lesions with MR imaging features of IP, (18)F-FDG PET/CT demonstrating avid FDG uptake does not necessarily imply the presence of coexistent malignancy. In our small series, although IPs containing foci of SCC had consistently higher SUVs than IPs without SCC, the limited literature on this subject suggests that PET cannot be used reliably to make the distinction.

Objective: The aim of this study was to assess the clinical role of (18)F-FDG PET/CT for the evaluation of lymph node metastasis in periorbital malignancies, compared with CT alone., Materials and Methods: We analyzed eighteen PET/CT and CT scans in 15 patients with biopsy-proven periorbital malignancies. We compared the diagnostic capabilities of PET/CT and CT with regard to nodal metastasis by level-by-level analysis and by N staging prediction. The reference standards were surgical pathology (n = 7) from dissected lymph node specimens and the results from radiological follow-up (n = 11, mean 20.5 months; range 10-52 months). Moreover, any changes in patient care as prompted by PET/CT were recorded and compared with treatment planning for CT alone., Results: PET/CT had a sensitivity of 100%, while CT had a sensitivity of 57% (p = 0.03) for nodal metastasis by level-by-level analysis. PET/CT had a specificity of 97%, positive predictive value of 93%, negative predictive value of 100%, and diagnostic accuracy of 98%, while the CT values for these same parameters were 97%, 89%, 82%, and 84%, respectively. PET/CT correctly predicted N staging with an accuracy of 100%, while CT was only 83% accurate (p = 0.01). Regarding the impact on patient care, the extent of surgery for regional lymph nodes and the treatment decision were modified by PET/CT in 39% of patients., Conclusion: PET/CT could provide useful information in the management of regional lymph node metastases in patients with periorbital malignancies.