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Objective To investigate the relationship between 18F-FDG maximum standardized uptake value （SUVmax） and epidermal growth factor receptor （EGFR） mutation in pulmonary adenocarcinoma and its different histologic subtypes. Methods The PET/CT imaging and clinicopathological data of 305 patients with lung adenocarcinoma confirmed by pathology were retrospectively analyzed. Clinicopathological data included age，diameter，gender，smoking status， metastasis，stage，pathological subtypes and differentiate grade.The factors related to EGFR mutation were analyzed by univariate and multivariate Logistic regression analysis.The scoring scale was made to predict EGFR mutation status. Results The overall mutation rate of EGFR was 63.6% （194/305）. EGFR mutation was significantly correlated with women （72.9% vs. 54.0%，P=0.001），non-smoking（68.2% vs. 46.0%，P=0.001），SUVmax≤5.5 （75.2% vs. 57.1%，P=0.006），and low and medium risk groups （67.4%，65.2% vs. 44.9%，P=0.012）. The score of the scoring scale was significantly correlated with EGFR mutation（P<0.001），and the score>2 was defined as the optimal cut-off value of the ROC curve with sensitivity of 64.4%，specificity of 59.6% and accuracy of 62.6%. Conclusion PET/CT has certain predictive value for EGFR mutation，and its predictive value is higher by combining clinic opathological data of patients with SUVmax. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to determine whether PET textural features measured with a new dedicated breast PET scanner reflect biological characteristics of breast tumors. Methods: One hundred and thirty-nine breast tumors from 127 consecutive patients were included in this analysis. All of them underwent a F-FDG PET scan before treatment. Well-known PET quantitative parameters such as SU V , SU V , metabolically active tumor volume (MATV) and total lesion glycolysis (TLG) were extracted. Together with these parameters, local, regional, and global heterogeneity descriptors, which included five textural features (TF), were computed. Immunohistochemical classification of breast cancer considered five subtypes: luminal A like (LA), luminal B like/HER2 − (LB −), luminal B like/HER2+ (LB+), HER2-positive-non-luminal (HER2pnl), and triple negative (TN). Associations between PET features and tumor characteristics were assessed using non-parametric hypothesis tests. Results: Along with well-established associations, new correlations were found. HER2-positive tumors had significantly higher uptake ( p < 0.001, AUCs > 0.70) and presented different global and regional heterogeneity ( p = 0.002, p = 0.016, respectively, AUCs < 0.70). Nine out of ten analyzed features were significantly associated with immunohistochemical subtype. Uptake was lower for LA tumors ( p < 0.001) with AUCs ranging from 0.71 to 0.88 for each subgroup comparison. Heterogeneity metrics were significantly associated when comparing LA and LB − ( p < 0.01), being regional heterogeneity metrics more discriminative than any other parameter (AUC = 0.80 compared to AUC = 0.71 for SUV). LB+ and HER2pnl tumors also showed more regional heterogeneity than LA tumors (AUCs = 0.79 and 0.84, respectively). After comparison with whole-body PET studies, we observed an overall improvement in the classification ability of both non-heterogeneity metrics and textural features. Conclusions: PET parameters extracted from high-resolution dedicated breast PET images showed new and stronger correlations with immunohistochemical factors and immunohistochemical subtype of breast cancer compared to whole-body PET. [ABSTRACT FROM AUTHOR]

A 60 year old woman who presented with multiple small subcutaneous nodules in the upper back and arms, was referred for an [18F] fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) after histological evaluation revealed metastatic leiomyosarcoma of unknown origin. The PET/CT showed multiple F-FDG-avid subcutaneous nodules, bone lesions, as well as a large left renal mass, which was biopsied to confirm a primary renal leiomyosarcoma arising from the renal parenchyma. A post therapy PET/CT showed overall progression of disease. The use of F-FDG PET/CT in the staging and evaluation of response to therapy of a renal leiomyosarcoma has not been previously described in the literature. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the incidence, location, and clinical significance of focal F-FDG uptake of the spinal cord in patients with cancer. Methods: We reviewed the medical records of 22,937 consecutive adult patients with known or suspicious malignancy who underwent F-FDG PET/CT. PET/CT scans with incidental focal spinal cord uptake were selected and retrospectively reviewed to determine the presence, location, number, and maximum standardized uptake value (SUV) of any focal hypermetabolic lesions of the spinal cord. In subjects with focal spinal uptake, clinical characteristics and clinical follow-up results, including follow-up PET/CT, were reviewed. Results: Incidental focal spinal cord uptake was observed in 69 of 22,937 adult patients (incidence = 0.3%; M:F = 31:38; age, 55.8 ± 14.7 years). Seventy-eight focal hypermetabolic lesions on spinal cord in the PET/CT scans of the 69 study subjects were analyzed. The most common sites of focal spinal cord uptake were the T12 vertebra (47/78; 60.3%) and L1 vertebra (20/78; 25.6%). Multifocal cord uptake was found in 8 of 69 patients (11.6%). The average SUV for cord uptake was 2.5 ± 0.5 (range, 1.4∼3.9). There was no clinical or imaging evidence of abnormalities in the spinal cord, both at the time of PET/CT and during clinical follow-up. Conclusions: Although incidental focal F-FDG uptake of the spinal cord is rare in patients with cancer, it may be physiological or benign, but it should not be considered as malignant involvement. Common sites for the uptake were in the T12 and L1 spine levels. [ABSTRACT FROM AUTHOR]

Background: F-FDG PET has been used in sarcoidosis for diagnosis and determination of the extent of the disease. However, assessing inflammatory lesions in cardiac sarcoidosis using F-FDG can be challenging because it accumulates physiologically in normal myocardium. Another radiotracer, 3′-deoxy-3′-F-fluorothymidine (F-FLT), has been investigated as a promising PET tracer for evaluating tumor proliferative activity. In contrast to F-FDG, F-FLT uptake in the normal myocardium is low. The purpose of this retrospective study was to compare the uptake of F-FLT and F-FDG in the evaluation of cardiac and extra-cardiac thoracic involvement in patients with newly diagnosed sarcoidosis. Data for 20 patients with newly diagnosed sarcoidosis were examined. F-FLT and F-FDG PET/CT studies had been performed at 1 h after each radiotracer injection. The patients had fasted for at least 18 h before F-FDG PET/CT but were given no special dietary instructions regarding the period before F-FLT PET/CT. Uptake of F-FLT and F-FDG was examined visually and semiquantitatively using maximal standardized uptake value (SUVmax). Results: Two patients had cardiac sarcoidosis, 7 had extra-cardiac thoracic sarcoidosis, and 11 had both cardiac and extra-cardiac thoracic sarcoidosis. On visual analysis for diagnosis of cardiac sarcoidosis, 4/20 F-FDG scans were rated as inconclusive because the F-FDG pattern was diffuse, whereas no FLT scans were rated as inconclusive. The sensitivity of F-FDG PET/CT for detection of cardiac sarcoidosis was 85%; specificity, 100%; and accuracy, 90%. The corresponding values for F-FLT PET/CT were 92, 100, and 95%, respectively. Using semiquantitative analysis of cardiac sarcoidosis, the mean F-FDG SUVmax was significantly higher than the mean F-FLT SUVmax ( P < 0.005). Both F-FDG and F-FLT PET/CT studies detected all 24 extra-cardiac lesions. Using semiquantitative analysis of extra-cardiac sarcoidosis, the mean F-FDG SUVmax was significantly higher than the mean F-FLT SUVmax ( P < 0.001). Conclusions: The results of this preliminary study suggest that F-FLT PET/CT can detect cardiac and extra-cardiac thoracic involvement in patients with newly diagnosed sarcoidosis as well as F-FDG PET/CT, although uptake of F-FLT in lesions was significantly lower than that of F-FDG. However, F-FLT PET/CT may be easier to perform since it requires neither prolonged fasting nor a special diet prior to imaging. [ABSTRACT FROM AUTHOR]

Purpose: Imaging tumor FDG uptake could complement breast cancer biomarkers of risk and treatment response. Although breast cancer FDG uptake is reputedly influenced by major biomarker states, the role of epidermal growth factor receptor (EGFR) expression remains largely unexplored. Methods: This is a retrospective study that included 499 patients with primary breast cancer at initial presentation. Tumor FDG uptake was measured on pretreatment PET/CT as maximum standardized uptake value (SUVmax), and biomarkers were assessed by immunohistochemistry of tumor tissue. Regression analysis was performed for predictors of high tumor FDG uptake (SUVmax ≥ 8.6). Results: SUVmax was higher in ER- (36.5%; 11.2 ± 6.0 vs. 8.3 ± 5.3), PR- (42.3%; 10.9 ± 6.0 vs. 8.2 ± 5.2), and triple-negative tumors (19.8%; 12.0 ± 6.9 vs. 8.7 ± 5.2; all p < 0.0001). EGFR expression (28.5%) was more frequent in ER-, PR-, triple-negative, cytokeratin 5/6 (CK5/6) + and mutant P53 (mP53) + tumors (all p < 0.0001). EGFR+ was associated with higher SUVmax among all tumors (11.9 ± 6.0 vs. 8.3 ± 5.3), ER- tumors ( p < 0.0001), PR- and + tumors ( p < 0.0001 and 0.027), hormone receptor- and + tumors ( p < 0.0001 and 0.004), human epidermal growth factor receptor 2 (HER2)- and + tumors ( p < 0.0001 and 0.006), non-triple negative tumors ( p < 0.0001), CK5/6- and + tumors ( p = 0.021 and <0.0001), and mP53- and + tumors ( p < 0.0001 and 0.008). Tumors had high FDG uptake in 73.2% of EGFR+ and 40.6% of EGFR- tumors. On regression analysis, significant multivariate predictors of high tumor FDG uptake were large size, EGFR+ and CK5/6+ for the entire subjects, and EGFR+ and CK5/6+ for ER- and hormone receptor negative subgroups. High FDG uptake was able to sub-stratify EGFR+ tumors that were more likely to be ER- and CK5/6+, and EGFR- tumors more likely to be mP53 +. Conclusions: Primary breast tumor FDG uptake is strongly influenced by EGFR status beyond that by other major biomarkers including hormone receptor and HER2 status, and EGFR expression is a strong independent predictor of high breast tumor FDG uptake. [ABSTRACT FROM AUTHOR]

Purpose & Methods: Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using Ga-DOTA-conjugated peptides, as well as F-DOPA imaging for various neuroendocrine neoplasms. Results & Conclusion: The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with Ga-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts. [ABSTRACT FROM AUTHOR]

Objective: Our study was designed to explore the utility of 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) for the detection of hepatocellular carcinoma (HCC) and specifically to compare the diagnostic performance of 99mTc-3PRGD2 integrin receptor imaging and 2-18-fluoro-2-deoxy-D-glucose (18F-FDG) metabolic imaging in a nude mouse model.Methods: 99mTc-3PRGD2 was synthesized using a HYNIC-3PRGD2 lyophilized kit with 99mTcO4 labelling. The nude mouse animal model was established by subcutaneously injecting 5 × 107/ml HepG2 cells into the shoulder flank of each mouse. Biodistribution studies were performed at 0.5, 1, 2 and 4 h after intravenous administration of 0.37 MBq of 99mTc-3PRGD2. Immunohistochemistry was performed to evaluate the expression level of integrin αvβ3 in the HCC tissues. Dynamic imaging was performed using list-mode after the administration of 55.5 MBq of 99mTc-3PRGD2, to reconstruct the multiphase images and acquire the best initial scan time. At 8, 12, 16, 20 and 24 days after inoculation with HepG2 cells, 55.5 MBq of 99mTc-3PRGD2 and 37 MBq of 18F-FDG were injected successively into the nude mouse model, subsequently, simultaneous SPECT/PET imaging was performed to calculate the tumour volume and tumour uptake of 99mTc-3PRGD2 and 18F-FDG.Results: The biodistribution study first validated that the tumour uptake of 99mTc-3PRGD2 at the different time points was higher than that of all the other organs tested in the experiment, except for the kidney. Integrin αvβ3 expressed highly in early stage HCC and declined for further necrosis of the tumour tissue. Subcutaneous tumours were visualized clearly with excellent contrast under 99mTc-3PRGD2 SPECT/CT imaging, and the multiphase imaging comparison showed the tumours were prominent at 0.5 h, suggesting that the best initial scan time is 0.5 h post-injection. The comparison of the imaging results of the two methods showed that 99mTc-3PRGD2 integrin receptor imaging was more sensitive than 18F-FDG metabolic imaging for the detection of early stage HCC, meanwhile the tumour uptake of 99mTc-3PRGD2 was consistently higher than that of 18F-FDG. However, as tumour necrosis further increased in HCC tissues, the uptake of 18F-FDG was higher than that of 99mTc-3PRGD2.Conclusion: Our study demonstrated that 99mTc-3PRGD2 is a valuable tumour molecular probe for the detection of early stage HCC compared with 18F-FDG, meriting further investigation of 99mTc-3PRGD2 as a novel SPECT tracer for tumour imaging. [ABSTRACT FROM AUTHOR]

Background: Simultaneous acquisition Positron emission tomography/magnetic resonance (PET/MR) is a new technology that has potential as a tool both in research and clinical diagnosis. However, cardiac PET acquisition has not yet been validated using MR imaging for attenuation correction (AC). The goal of this study is to evaluate the feasibility of PET imaging using a standard 2-point Dixon volume interpolated breathhold examination (VIBE) MR sequence for AC.Methods and Results: Evaluation was performed in both phantom and patient data. A chest phantom containing heart, lungs, and a lesion insert was scanned by both PET/MR and PET/CT. In addition, 30 patients underwent whole-body 18F-fluorodeoxyglucose PET/CT followed by simultaneous cardiac PET/MR. Phantom study showed 3% reduction of activity values in the myocardium due to the non-inclusion of the phased array coil in the AC. In patient scans, average standardized uptake values (SUVs) obtained by PET/CT and PET/MR showed no significant difference (n = 30, 4.6 ± 3.5 vs 4.7 ± 2.8, P = 0.47). There was excellent per patient correlation between the values acquired by PET/CT and PET/MR (R 2 = 0.97).Conclusions: Myocardial SUVs PET imaging using MR for AC shows excellent correlation with myocardial SUVs obtained by standard PET/CT imaging. The 2-point Dixon VIBE MR technique can be used for AC in simultaneous PET/MR data acquisition. [ABSTRACT FROM AUTHOR]

Objective: One of the major causes of diabetes and obesity is abnormality in glucose metabolism and glucose uptake in the muscle and adipose tissue based on an insufficient action of insulin. Therefore, many of the drug discovery programs are based on the concept of stimulating glucose uptake in these tissues. Improvement of glucose metabolism has been assessed based on blood parameters, but these merely reflect the systemic reaction to the drug administered. We have conducted basic studies to investigate the usefulness of glucose uptake measurement in various muscle and adipose tissues in pharmacological tests using disease-model animals.Methods: A radiotracer for glucose, 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG), was administered to Wistar fatty rats (type 2 diabetes model), DIO mouse (obese model), and the corresponding control animals, and the basal glucose uptake in the muscle and adipose (white and brown) tissues were compared using biodistribution method. Moreover, insulin and a β3 agonist (CL316,243), which are known to stimulate glucose uptake in the muscle and adipose tissues, were administered to assess their effect. 18F-FDG uptake in each tissue was measured as the radioactivity and the distribution was confirmed by autoradiography.Results: In Wistar fatty rats, all the tissues measured showed a decrease in the basal level of glucose uptake when compared to Wistar lean rats. On the other hand, the same trend was observed only in the white adipose tissue in DIO mice, while brown adipose tissue showed increments in the basal glucose uptake in this model. Insulin administration stimulated glucose uptake in both Wistar lean and fatty rats, although the responses were inhibited in Wistar fatty rats. The same tendency was shown also in control mice, but clear increments in glucose uptake were not observed in the muscle and brown adipose tissue of DIO mice after insulin administration. β3 agonist administration showed the similar trend in Wistar lean and fatty rats as insulin, while the responses were inhibited in the adipose tissues of Wistar fatty rats.Conclusion: A system to monitor tissue glucose uptake with 18F-FDG enabled us to detect clear differences in basal glucose uptake between disease-model animals and their corresponding controls. The responses in the tissues to insulin or β3 agonist could be identified. Taken as a whole, the biodistribution method with 18F-FDG was confirmed to be useful for pharmacological evaluation of anti-diabetic or anti-obesity drugs using disease-model animals. [ABSTRACT FROM AUTHOR]

Background: We investigated the relationship between metabolic activity and histological features of gliomas using fluorine-18α-methyltyrosine (F-FAMT) positron emission tomography (PET) compared with fluorine-18 fluorodeoxyglucose (F-FDG) PET in 38 consecutive glioma patients. The tumor to normal brain ratios (T/N ratios) were calculated, and the relationships between T/N ratio and World Health Organization tumor grade or MIB-1 labeling index were evaluated. The diagnostic values of T/N ratios were assessed using receiver operating characteristic (ROC) curve analyses to differentiate between high-grade gliomas (HGGs) and low-grade gliomas (LGGs). Results: Median T/N ratio of F-FAMT PET was 2.85, 4.65, and 4.09 for grade II, III, and IV gliomas, respectively, with significant differences between HGGs and LGGs ( p = 0.006). Both T/N ratio ( p = 0.016) and maximum standardized uptake value ( p = 0.033) of F-FDG PET showed significant differences between HGGs and LGGs. ROC analysis yielded an optimal cut-off of 3.37 for the T/N ratio of F-FAMT PET to differentiate between HGGs and LGGs (sensitivity 81%, specificity 67%, accuracy 76%, area under the ROC curve 0.776). Positive predictive value was 84%, and negative predictive value was 62%. T/N ratio of F-FAMT PET was not correlated with MIB-1 labeling index in all gliomas, whereas T/N ratio of F-FDG PET was positively correlated ( r = 0.400, p = 0.013). Significant positive correlation was observed between T/N ratios of F-FDG and F-FAMT ( r = 0.454, p = 0.004), but median T/N ratio of F-FAMT PET was significantly higher than that of F-FDG PET in all grades of glioma. Conclusions: The T/N ratio of F-FAMT uptake has high positive predictive value for detection of HGGs. F-FAMT PET had higher T/N ratio, with better tumor-normal brain contrast, compared to F-FDG PET in both LGGs and HGGs. Therefore, F-FAMT is a useful radiotracer for the preoperative visualization of gliomas. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the consistency of PET evaluation response criteria in solid tumours (PERCIST) and European Organisation for Research and Treatment of Cancer (EORTC) classification across different reconstruction algorithms and whether aligning standardized uptake values (SUVs) to the European Association of Nuclear Medicine acquisition (EANM)/EARL standards provides more consistent response classification. Materials and methods: Baseline () and response assessment () scans in 61 patients with non-small cell lung cancer were acquired in protocols compliant with the EANM guidelines and were reconstructed with point-spread function (PSF) or PSF + time-of-flight (TOF) reconstruction for optimal tumour detection and with a standardized ordered subset expectation maximization (OSEM) reconstruction known to fulfil EANM harmonizing standards. Patients were recruited in three centres. Following reconstruction, EQ.PET, a proprietary software solution was applied to the PSF ± TOF data (PSF ± TOF.EQ) to harmonize SUVs to the EANM standards. The impact of differing reconstructions on PERCIST and EORTC classification was evaluated using standardized uptake values corrected for lean body mass (SUL). Results: Using OSEM/OSEM (standard scenario), responders displayed a reduction of −57.5% ± 23.4 and −63.9% ± 22.4 for SUL and SUL, respectively, while progressing tumours had an increase of +63.4% ± 26.5 and +60.7% ± 19.6 for SUL and SUL respectively. The use of PSF ± TOF reconstruction impacted the classification of tumour response. For example, taking the OSEM/PSF ± TOF scenario reduced the apparent reduction in SUL in responding tumours (−39.7% ± 31.3 and −55.5% ± 26.3 for SUL and SUL, respectively) but increased the apparent increase in SUL in progressing tumours (+130.0% ± 50.7 and +91.1% ± 39.6 for SUL and SUL, respectively). Consequently, variation in reconstruction methodology (PSF ± TOF/OSEM or OSEM /PSF ± TOF) led, respectively, to 11/61 (18.0%) and 10/61 (16.4%) PERCIST classification discordances and to 17/61 (28.9%) and 19/61 (31.1%) EORTC classification discordances. An agreement was better for these scenarios with application of the propriety filter, with kappa values of 1.00 and 0.95 compared to 0.75 and 0.77 for PERCIST and kappa values of 0.93 and 0.95 compared to 0.61 and 0.55 for EORTC, respectively. Conclusion: PERCIST classification is less sensitive to reconstruction algorithm-dependent variability than EORTC classification but harmonizing SULs within the EARL program is equally effective with either. [ABSTRACT FROM AUTHOR]

Background: An inflammatory reaction in the airways and lung parenchyma, comprised mainly of neutrophils and alveolar macrophages, is present in some patients with chronic obstructive pulmonary disease (COPD). Thoracic fluorodeoxyglucose (F-FDG) positron emission tomography (PET) has been proposed as a promising imaging biomarker to assess this inflammation. We sought to introduce a fully quantitative analysis method and compare this with previously published studies based on the Patlak approach using a dataset comprising F-FDG PET scans from COPD subjects with elevated circulating inflammatory markers (fibrinogen) and matched healthy volunteers (HV). Dynamic F-FDG PET scans were obtained for high-fibrinogen (>2.8 g/l) COPD subjects ( N = 10) and never smoking HV ( N = 10). Lungs were segmented using co-registered computed tomography images and subregions (upper, middle and lower) were semi-automatically defined. A quantitative analysis approach was developed, which corrects for the presence of air and blood in the lung ( qABL method), enabling direct estimation of the metabolic rate of FDG in lung tissue. A normalised Patlak analysis approach was also performed to enable comparison with previously published results. Effect sizes (Hedge's g) were used to compare HV and COPD groups. Results: The qABL method detected no difference (Hedge's g = 0.15 [−0.76 1.04]) in the tissue metabolic rate of FDG in the whole lung between HV ( μ = 6.0 ± 1.9 × 10 ml cm min) and COPD ( μ = 5.7 ± 1.7 × 10 ml cm min). However, analysis with the normalised Patlak approach detected a significant difference (Hedge's g = −1.59 [−2.57 −0.48]) in whole lung between HV ( μ = 2.9 ± 0.5 × 10 ml cm min) and COPD ( μ = 3.9 ± 0.7 × 10 ml cm min). The normalised Patlak endpoint was shown to be a composite measure influenced by air volume, blood volume and actual uptake of F-FDG in lung tissue. Conclusions: We have introduced a quantitative analysis method that provides a direct estimate of the metabolic rate of FDG in lung tissue. This work provides further understanding of the underlying origin of the F-FDG signal in the lung in disease groups and helps interpreting changes following standard or novel therapies. [ABSTRACT FROM AUTHOR]

Background: Positron emission tomography-computed tomography (PET-CT) carotid standardised uptake values (SUV) of F-fluorodeoxyglucose (FDG) have been proposed as an inflammatory biomarker for determining cerebrovascular diseases such as stroke. Consideration of varying methodological approaches and software packages is critical to the calculation of accurate SUVs in cross-sectional and longitudinal patient studies. The aim of this study was to investigate whether or not carotid atherosclerotic plaque SUVs are consistent and reproducible between software packages. FDG-PET SUVs of carotids were taken in 101 patients using two different software packages. Quality assurance checks were performed to standardise techniques before commencing the analysis where data from five to seven anatomical sites were measured. A total of ten regions of interest were drawn on each site analysed. Statistical analyses were then performed to compare SUV measurements from the two software packages and to explore reproducibility of measurements. Lastly, the time taken to complete each analysis was measured and compared. Results: Statistically significant differences in SUV measurements, between the two software packages, ranging from 9 to 21.8% were found depending on ROI location. In 79% ( n = 23) of the ROI locations, the differences between the SUV measurements from each software package were found to be statistically significant. The time taken to perform the analyses and export data from the software packages also varied considerably. Conclusions: This study highlights the importance of standardising all aspects of methodological approaches to ensure accuracy and reproducibility. Physicians must be aware that when a PET-CT data set is analysed, subsequent follow-ups must be verified, if possible, with the same software package or cross-calibration between packages should be performed. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. In ALS, both glucose consumption and neuronal intensity reportedly decrease in the cerebral motor cortex when measured by positron emission tomography (PET). In this study, we evaluated cervical spinal glucose metabolism, blood flow, and neuronal intensity of 10 ALS patients with upper extremity (U/E) atrophy both with 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) PET and 11C-flumazenil (11C-FMZ) PET. On the ipsilateral side of C5 and T1 levels, 18F-FDG uptake increased significantly (*p < 0.05), and was correlated with the rate of progression of the ALS FRS-R-U/E score (R = 0.645, *p = 0.041). Despite this hyperglucose metabolism, the 11C-FMZ PET study did not show a coupled increase of spinal blood flow even though neuronal intensity did not decrease. These results indicate a strong correlation between hyperglucose metabolism and ALS progression alongside the uncoupling of flow-metabolism. This mechanism, which could result in subsequent motor neuronal death, may be a potential therapeutic target for ALS. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) or PET/computed tomography (CT) using F-3′-fluoro-3′-deoxythymidine (F-FLT) offers noninvasive assessment of cell proliferation in human cancers in vivo. The present review discusses the current status on clinical applications of F-FLT-PET (or PET/CT) in digestive and abdominal oncology by comparing with F-fluorodeoxyglucose (F-FDG)-PET (or PET/CT). The results of this review show that although F-FLT uptake is lower in most cases of digestive and abdominal malignancies compared with F-FDG uptake, F-FLT-PET can be used to detect primary tumors. F-FLT-PET has shown greater specificity for N staging than F-FDG-PET which can show false-positive uptake in areas of inflammation. However, because of the high background uptake in the liver and bone marrow, it has a limited role of assessing liver and bone metastases. Instead, F-FLT-PET will be a powerful tool for monitoring response to treatment and provide prognostic information in digestive and abdominal oncology. [ABSTRACT FROM AUTHOR]

Background: Red blood cells (RBCs) labeled with single-photon emitters have been clinically used for blood-pool imaging. Although some PET tracers have been introduced for blood-pool imaging, they have not yet been widely used. The present study investigated the feasibility of labeling RBCs with F-2-deoxy-2-fluoro-D-glucose (F-FDG) for blood-pool imaging with PET. RBCs isolated from venous blood of rats were washed with glucose-free phosphate-buffered saline and labeled with F-FDG. To optimize labeling efficiency, the effects of glucose deprivation time and incubation (labeling) time with F-FDG were investigated. Post-labeling stability was assessed by calculating the release fraction of radioactivity and identifying the chemical forms of F in the released and intracellular components of F-FDG-labeled RBCs incubated in plasma. Just after intravenous injection of the optimized autologous F-FDG-labeled RBCs, dynamic PET scans were performed to evaluate in vivo imaging in normal rats and intraabdominal bleeding models (temporary and persistent bleeding). Results: The optimal durations of glucose deprivation and incubation (labeling) with F-FDG were 60 and 30 min, respectively. As low as 10% of F was released as the form of F-FDG from F-FDG-labeled RBCs after a 60-min incubation. Dynamic PET images of normal rats showed strong persistence in the cardiovascular system for at least 120 min. In the intraabdominal bleeding models, F-FDG-labeled RBC PET visualized the extravascular blood clearly and revealed the dynamic changes of the extravascular radioactivity in the temporary and persistent bleeding. Conclusions: RBCs can be effectively labeled with F-FDG and used for blood-pool imaging with PET in rats. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to assess the combined use of the radiotracers F-FDG and F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). Patients and methods: Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with F-FDG and F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). Results: An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, F-FDG PET/CT-based treatment response revealed CR in 14 patients (F-FDG PET/CT CR), PR in 11 patients (F-FDG PET/CT PR) and progressive disease in four patients (F-FDG PET/CT PD). In terms of F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, F-NaF PET/CT depicted 56 of the 129 F-FDG positive lesions (43 %). Follow-up F-NaF PET/CT showed persistence of 81.5 % of the baseline F-NaF positive MM lesions after treatment, despite the fact that 64.7 % of them had turned to F-FDG negative. Treatment response according to F-NaF PET/CT revealed CR in one patient (F-NaF PET/CT CR), PR in five patients (F-NaF PET/CT PR), SD in 12 patients (F-NaF PET/CT SD), and PD in seven patients (F-NaF PET/CT PD). Dynamic F-FDG and F-NaF PET/CT studies showed that SUV, SUV, as well as the kinetic parameters K, influx and FD from reference bone marrow and skeleton responded to therapy with a significant decrease ( p < 0.001). Conclusion: F-FDG PET/CT demonstrated a sensitivity of 57.7 % and a specificity of 100 % in treatment response evaluation of MM. Despite its limited sensitivity, the performance of F-FDG PET/CT was satisfactory, given that 6/9 false negative patients in follow-up scans (66.7 %) were clinically characterized as nCR, a disease stage with very low tumor mass. On the other hand, F-NaF PET/CT does not seem to add significantly to F-FDG PET/CT in treatment response evaluation of MM patients undergoing HDT and ASCT, at least shortly after therapy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical implications of lymph node (LN) density on F-FDG PET/CT for mediastinal LN characterization in non-small cell lung cancer (NSCLC). Methods: One hundred and fifty-two patients with 271 mediastinal LNs who underwent PET/CT and endobronchial ultrasound-guided transbronchial needle aspiration for staging were enrolled. Maximum standardized uptake value (SUVmax), short axis diameter, LN-to-primary cancer ratio of SUVmax, and median Hounsfield unit (HU) based on CT histogram were correlated to histopathology. Results: Of 271 nodes, 162 (59.8 %) were malignant. SUVmax, short axis diameter, and LPR of malignant LNs were higher than those of benign nodes. Among malignant LNs, 71.0 % had median HU between 25 and 45, while 78.9 % of benign LNs had values <25 HU or >45 HU. Using a cutoff value of 4.0, SUVmax showed the highest diagnostic ability for detecting malignant LNs with a specificity of 94.5 %, but showing a sensitivity of 70.4 %. Using additional density criteria (median HU 25-45) in LNs with 2.0< SUVmax ≤4.0, the sensitivity increased to 88.3 % with the specificity of 82.6 %. Conclusions: LN density is useful for the characterization of LNs with mild F-FDG uptake. The risk of mediastinal LN metastasis in NSCLC patients could be further stratified using both F-FDG uptake and LN density. Key Points : • SUVmax showed the highest diagnostic ability for detecting malignant LNs. • LN density was useful in characterization of LNs with mild FDG uptake. • SUVmax and LN density together could stratify the risk of LN metastasis. [ABSTRACT FROM AUTHOR]

Giant cell tumor (GCT) is a generally benign bone tumor accounting for approximately 5 % of all primary bone neoplasms. Cystic components in GCTs that indicate secondary aneurysmal bone cysts (ABCs) are reported in 14 % of GCTs. Although both of them have been described separately in previous reports that may show considerable fluorodeoxyglucose (FDG) uptake despite their benign nature, the findings of GCT with secondary ABC on F-FDG positron emission tomography/computed tomography (PET/CT) have not been well-known. We report a case of GCT with secondary ABC in a 26-year-old woman. F-FDG PET/CT revealed a heterogeneous hypermetabolic lesion in the left proximal femur with the maximum standardized uptake value of 4.7. The solid components of the tumor showed higher FDG uptake than the cystic components. These observations suggest that the ABC components in GCTs show heterogeneous metabolic patterns on F-FDG PET/CT. [ABSTRACT FROM AUTHOR]

Objectives: Hypoxia is a key element involved in the development and progression of tumors. HIF-1α may transiently induce and mediate the response to acute and severe hypoxia, while HIF-2α may induce a longer response and may control the response to chronic and moderate hypoxia. Hypoxia increases the cellular uptake of FDG. Therefore, HIF may play an important role in the process of the cellular uptake of FDG. The aim of this study was to compare HIF-1α/HIF-2α expression with FDG uptake, Glut-1 expression, and prognosis in the patients with lung adenocarcinoma and to investigate the role of HIF-1α/HIF-2α in the uptake of FDG in lung adenocarcinoma.Methods: In the current work, we compared the immunohistochemical expression of HIF-1α and HIF-2α in surgical specimens of 44 patients with lung adenocarcinoma. The relationships between HIF-α expression and Glut-1 expression, FDG uptake, and clinicopathological factors, including prognosis, were analyzed.Results: There was a marginal association between HIF-1α and HIF-2α expressions (P = 0.076). We found a significant correlation between HIF-2α expression and FDG uptake (P = 0.0001). HIF-1α expression showed a marginal association with FDG uptake (P = 0.066). FDG uptake correlated more significantly with HIF-2α expression than with HIF-1α expression. A significant correlation was noticed between Glut-1 expression and both HIF-1α and HIF-2α expressions (P = 0.005 and P = 0.003, respectively). Univariate analysis of disease-free survival demonstrated that FDG uptake and HIF-2α expression, but not HIF-1α expression, were related to recurrence (P < 0.0001).Conclusion: FDG uptake correlated more significantly with HIF-2α expression than with HIF-1α expression, and both FDG uptake and HIF-2α expression, but not HIF-1α expression was correlated with post-operative recurrence in the patients with lung adenocarcinoma. These results suggest that both FDG uptake and HIF-2α expression may represent a more aggressive phenotype and that HIF-2α may play a more important role than HIF-1α in the uptake of FDG in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose: Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). Ga-DOTA(0)-Tyr(3)-octreotate (Ga-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of Ga-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT. Methods: This prospective study included 22 patients (15 men, 7 women; aged 50.0 ± 13.9 years) with confirmed metastatic PPGL, a negative family history for PPGL, and negative genetic testing, who underwent Ga-DOTATATE, F-fluoro-2-deoxy-D-glucose (F-FDG) PET/CT, and CT/MRI. Only 12 patients underwent an additional F-fluorodihydroxyphenylalanine (F-FDOPA) PET/CT scan and only 11 patients underwent an additional F-fluorodopamine (F-FDA) PET/CT scan. The rates of detection of metastatic lesions were compared among all the imaging studies. A composite of all functional and anatomical imaging studies served as the imaging comparator. Results: Ga-DOTATATE PET/CT showed a lesion-based detection rate of 97.6 % (95 % confidence interval, CI, 95.8 - 98.7 %). F-FDG PET/CT, F-FDOPA PET/CT, F-FDA PET/CT, and CT/MRI showed detection rates of 49.2 % (CI 44.5 - 53.6 %; p < 0.01), 74.8 % (CI 69.0 - 79.9 %); p < 0.01), 77.7 % (CI 71.5 - 82.8 %; p < 0.01), and 81.6 % (CI 77.8 - 84.8 %; p < 0.01), respectively. Conclusion: The results of this study demonstrate the superiority of Ga-DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality. [ABSTRACT FROM AUTHOR]

Purpose: Following Achilles tendon rupture, running is often allowed after 6 months. However, tendon healing is slow and the metabolic status of the tendon at this point is unknown. The purpose of this study was to investigate tendon metabolism (glucose uptake) and vascularization at 3, 6 and 12 months after Achilles tendon rupture as measured using PET and power Doppler ultrasonography (PDUS). Methods: The study group comprised 23 patients with surgically repaired Achilles tendon rupture who were investigated at 3 months ( n = 7), 6 months ( n = 7) and 12 months ( n = 9) after surgery. The triceps surae complex was loaded over 20 min of slow treadmill walking while a radioactive tracer (F-FDG) was administered prior to PET. Vascularization was measured in terms of PDUS flow activity, and patient-reported outcomes were scored using the Achilles tendon rupture score (ATRS) and sports assessment (VISA-A) questionnaire. Results: Relative glucose uptake (F-FDG) was higher in repaired tendons than in intact tendons at all time-points (6, 3 and 1.6 times higher at 3, 6 and 12 months, respectively; P ≤ 0.001), and was also higher in the tendon core than in the periphery at 3 and 6 months ( P ≤ 0.02), but lower at 12 months ( P = 0.06). Relative glucose uptake was negatively related to ATRS at 6 months after repair ( r = −0.89, P ≤ 0.01). PDUS flow activity was higher in repaired tendons than in intact tendons at 3 and 6 months ( P < 0.05 for both), but had normalized by 12 months. Conclusion: These data demonstrate that the healing process as determined by metabolic activity and vascularization continues for 6 months after injury when large loads are typically allowed on the tendon. Indeed, metabolic activity remained elevated for more than 1 year after injury despite normalized vascularization. The robust negative correlation between tendon metabolism and patient-reported outcome suggests that a high metabolic activity 6 months after the injury may be related to a poor clinical healing outcome. [ABSTRACT FROM AUTHOR]

Background: The recent spread of positron emission tomography-computed tomography (PET/CT) poses extremity dosimetry challenges. The question arose whether the radiation dose measured by the ring thermoluminescent dosimeter usually worn on the proximal phalanx (P1) of the index finger measures doses that are representative of the true doses received by the upper extremities of the operators. A prospective individual dosimetry study was performed in which the personal equivalent dose Hp (0.07) received during a specific 2-[F]fluoro-2-deoxy- d-glucose (F-FDG) manual dose-dispensing procedure was measured in a paired design by two operational personal electronic dosimeters fitted on the palm side of the index finger, namely in the P1 and distal phalanx (P3) positions. The study participants were ten nuclear medicine technologists working in two nuclear medicine departments. The personal equivalent radiation doses received by the palm side of the proximal phalanx of the index finger [Hp (0.07)] and that received by the distal phalanx [Hp (0.07)] were compared. Results: The median Hp (0.07)/Hp (0.07) ratio per participant varied between 1.0 and 2.5 (based on 23 to 31 measurements per participant). The 271 paired measurements revealed a crude Hp (0.07)/Hp (0.07) ratio of 1.67, significantly different from 1 ( p = 0.0004, 95 % CI [1.35-2.07]). When adjusted on participant's gender and mother vial activity, the ratio was similar (1.53, p = 0.003, 95 % CI [1.22-1.92]). Conclusions: The study demonstrated a significant disparity that may exist between the radiation doses measured in the P1 and P3 positions of operators during F-FDG manipulation. These findings emphasize the importance of performing workplace dosimetry studies adapted to each radiopharmaceutical and manipulation thereof, aiming to guarantee optimal workers' dosimetry monitoring schemes. Trial registration: Hospital Nursing and Paramedical Research Program (PHRIP, 2011-2013) from the French Ministry of Health (DGOS), [ABSTRACT FROM AUTHOR]

Purpose: To determine the value of Ga-DOTA-TOC and F-FDG PET/CT for initial and follow-up evaluation of patients with neuroendocrine tumour (NET) treated with peptide receptor radionuclide therapy (PRRT). Methods: We evaluated 66 patients who had histologically proven NET and underwent both PRRT and three combined Ga-DOTA-TOC and F-FDG PET/CT studies. Ga-DOTA-TOC PET/CT was performed before PRRT, 3 months after completion of PRRT and after a further 6 - 9 months. F-FDG PET/CT was done within 2 months of Ga-DOTA-TOC PET/CT. Follow-up ranged from 11.8 to 80.0 months (mean 34.5 months). Results: All patients were Ga-DOTA-TOC PET-positive initially and at follow-up after the first full PRRT cycle. Overall, 62 of the 198 F-FDG PET studies (31 %) were true-positive in 38 of the 66 patients (58 %). Of the 66 patients, 28 (5 grade 1, 23 grade 2) were F-FDG-negative initially and during follow-up (group 1), 24 (5 grade 1, 13 grade 2, 6 grade 3) were F-FDG-positive initially and during follow-up (group 2), 9 patients (2 grade 1, 6 grade 2, 1 grade 3) were F-FDG-negative initially but F-FDG-positive during follow-up (group 3), and 5 patients (all grade 2) were F-FDG-positive initially but F-FDG-negative during follow-up (group 4).F-FDG PET showed more and/or larger metastases than Ga-DOTA-TOC PET in five patients of group 2 and four patients of group 3, all with progressive disease. In three patients with progressive disease who died during follow-up tumour SUVmax increased by 41 - 82 % from the first to the last follow-up investigation. Conclusion: In NET patients, the presence of F-FDG-positive tumours correlates strongly with a higher risk of progression. Initially, patients with F-FDG-negative NET may show F-FDG-positive tumours during follow-up. Also patients with grade 1 and grade 2 NET may have F-FDG-positive tumours. Therefore, F-FDG PET/CT is a complementary tool to Ga-DOTA-TOC PET/CT with clinical relevance for molecular investigation. [ABSTRACT FROM AUTHOR]

This review addresses progress in the radionuclide diagnosis of oncological diseases using radiopharmaceutical preparations (RPP) based on labeled glucose derivatives. Most attention is paid to 2-[F]fluoro-2-deoxy-D-glucose (F-FDG), a glucose analog labeled with fluorine-18 ( T = 110 min) and the only radiotracer for glycolysis, which is used in 90% of clinical studies using positron emission tomography (PET). We describe approaches to the synthesis of F-FDG and state-of-the-art automated technologies allowing tens of clinical doses of RPP for PET investigations of patients to be prepared. The main areas of use of PET with F-FDG in the diagnosis of various tumors are discussed, as is the potential for using glucose derivatives with other radionuclides (Ga, I, Tc, Re) as tracers for use in PET and SPECT diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: PET with F-FDG has the potential to assess vascular macrophage metabolism. F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques. Methods: The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUV) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated. Results: Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUV values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3 ± 0.6 vs. 3.1 ± 0.6; P < 0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman's r = 0.67, P < 0.01). In contrast, TBR values of plaque lesions were similar on PET/MRI and on PET/CT (2.2 ± 0.3 vs. 2.2 ± 0.3; P = 0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman's r = 0.73, P < 0.01). Considering the increasing trend in SUV and TBR values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBR values may also be expected with PET/MRI compared with PET/CT. Conclusion: SUV and TBR values are widely accepted reference parameters for estimation of the radioactivity of atherosclerotic plaques on PET/CT. However, due to a systematic underestimation of SUV and TBR with PET/MRI, the optimal cut-off values indicating the presence of inflamed plaque tissue need to be newly defined for PET/MRI. [ABSTRACT FROM AUTHOR]

Purpose: In this prospective study, our goal was to emphasize the diagnostic value of combining C-choline and F-FDG PET/CT for hepatocellular carcinoma (HCC) in patients with chronic liver disease. Methods: Thirty-three consecutive patients were enrolled. All patients were suspected to have HCC based on CT and/or MRI imaging. A final diagnosis was obtained by histopathological examination or by imaging alone according to American Association for the Study of Liver Disease criteria. All patients underwent PET/CT with both tracers within a median of 5 days. All lesions showing higher tracer uptake than normal liver were considered positive for HCC. We examined how tracer uptake was related to biological (serum α-fetoprotein levels) and pathological (differentiation status, peritumoral capsule and vascular invasion) prognostic markers of HCC, as well as clinical observations at 6 months (recurrence and death). Results: Twenty-eight HCC, four cholangiocarcinomas and one adenoma were diagnosed. In the HCC patients, the sensitivity of C-choline, F-FDG and combined C-choline and F-FDG PET/CT for the detection of HCC was 75 %, 36 % and 93 %, respectively. Serum α-fetoprotein levels >200 ng/ml were more frequent among patients with F-FDG-positive lesions than those with F-FDG-negative lesions ( p < 0.05). Early recurrence ( n=2) or early death ( n=5) occurred more frequently in patients with F-FDG-positive lesions than in those with F-FDG-negative lesions ( p < 0.05). Conclusion: The combined use of C-choline and F-FDG PET/CT detected HCC with high sensitivity. This approach appears to be of potential prognostic value and may facilitate the selection of patients for surgical resection or liver transplantation. [ABSTRACT FROM AUTHOR]

Purpose: Twelve years ago a meta-analysis evaluated the diagnostic performance of F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in assessing musculoskeletal soft tissue lesions (MsSTL). Currently, PET/CT has substituted PET imaging; however, there has not been any published meta-analysis on the use of PET/CT or a comparison of PET/CT with PET in the diagnosis of MsSTL. Therefore, we conducted a meta-analysis to identify the current diagnostic performance of F-FDG PET/CT and determine if there is added value when compared to PET. Methods: A systematic review of English articles was conducted, and MEDLINE PubMed, the Cochrane Library, and Embase were searched from 1996 to March 2015. Studies exploring the diagnostic accuracy of F-FDG PET/CT (or dedicated PET) compared to histopathology in patients with MsSTL undergoing investigation for malignancy were included. Results: Our meta-analysis included 14 articles composed of 755 patients with 757 soft tissue lesions. There were 451 (60 %) malignant tumors and 306 benign lesions. The F-FDG PET/CT (and dedicated PET) mean sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for diagnosing MsSTL were 0.96 (0.90, 1.00), 0.77 (0.67, 0.86), 0.88 (0.85, 0.91), 0.86 (0.78, 0.94), and 0.91 (0.83, 0.99), respectively. The posterior mean (95 % highest posterior density interval) for the AUC was 0.92 (0.88, 0.96). PET/CT had higher specificity, accuracy, and positive predictive value when compared to a dedicated PET (0.85, 0.89, and 0.91 vs 0.71, 0.85, and 0.82, respectively). Conclusion: F-FDG PET/CT and dedicated PET are both highly accurate in the diagnosis of MsSTL. PET/CT is more accurate and specific and has a higher positive predictive value than PET. [ABSTRACT FROM AUTHOR]

Background: Hypoxia is associated with resistance to chemotherapy and radiotherapy and is randomly distributed within malignancies. Characterization of changes in intratumoral hypoxic regions is possible with specially developed PET tracers such as F-fluoroazomycin arabinoside (F-FAZA) while tumor metabolism can be measured with 2-deoxy-2-[F]fluoro- d-glucose (F-FDG). The purpose of this study was to study the effects of chemotherapy on F-FAZA and F-FDG uptake simultaneously in non-small-cell lung cancer (NSCLC) patients Methods: At baseline and after the second chemotherapy cycle, both PET/CT with F-FDG and F-FAZA was performed in seven patients with metastasized NSCLC. F-FAZA and F-FDG scans were aligned with deformable image registration using Mirada DBx. The primary tumors were contoured, and on the F-FDG scan, volumes of interest (VOI) were drawn using a 41 % adaptive threshold technique. Subsequently, the resulting VOI was transferred to the F-FAZA scan. F-FAZA maximum tumor-to-background (T/Bg) ratio and the fractional hypoxic volume (FHV) were assessed. Measurements were corrected for partial volume effects. Finally, a voxel-by-voxel analysis of the primary tumor was performed to assess regional uptake differences. Results: In the primary tumor of all seven patients, median F-FDG standard uptake value (SUV) decreased significantly ( p = 0.03). There was no significant decrease in F-FAZA uptake as measured with T/Bg ( p = 0.24) or the FHV ( p = 0.35). Additionally, volumetric voxel-by-voxel analysis showed that low hypoxic tumors did not significantly change in hypoxic status between baseline and two cycles of chemotherapy, whereas highly hypoxic tumors did. Individualized volumetric voxel-by-voxel analysis revealed that hypoxia and metabolism were not associated before and after 2 cycles of chemotherapy. Conclusions: Tumor hypoxia and metabolism are independent dynamic events as measured by F-FAZA PET and F-FDG PET, both prior to and after treatment with chemotherapy in NSCLC patients. [ABSTRACT FROM AUTHOR]

Purpose: Small-cell cervical cancer (SCCC) is rare and prone to metastasize. We conducted a prospective study to evaluate the role of F-FDG PET in the management of this aggressive malignancy. Methods: Patients with untreated primary, histologically confirmed SCCC were enrolled. F-FDG PET (or PET/CT) was performed immediately after MRI or CT, for primary staging, monitoring response to treatment or restaging when there was suspicion of recurrence. The clinical impact of PET was determined on a scan basis. Results: A total of 25 patients were recruited and 43 PET scans were performed. The PET images were obtained for primary staging (25 patients), monitoring response (10 patients) and restaging when there was suspicion of recurrence (8 patients). The median follow-up time in event-free patients was 109.3 months (range 97.5 - 157.7 months). A positive impact of PET was found in 8 (18.6 %) of the 43 scans, which included detection of additional regions of distal lymph node (LN) metastasis (one primary staging scan, two restaging scans), bone metastasis (two primary staging scans, one monitoring response scan), and exclusion of false-positive lesions on MRI (one primary staging scan, one restaging scan). On the other hand, one negative impact was recorded as one false-positive lesion on a restaging PET scan. One positive impact was noted for monitoring response (bone metastasis). The impact of three scans was indeterminate. The positive impact of down-staging in avoiding overtreatment but finding additional distal LN (except one on restaging) or bone metastases had no beneficial effect on long-term survival. Conclusion: The results of this preliminary study suggest that PET is useful in the management of SCCC. PET could have more value in detecting occult metastases if future novel therapies are able to offer better control of extensive SCCC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the accuracy of PET/CT using (18)F-fluorodeoxyglucose (FDG) with IV contrast for suspected recurrent head and neck squamous cell carcinoma (HNSCC).Methods: One hundred and seventy patients previously treated for HNSCC underwent PET/CT, consisting of non-contrast-enhanced and contrast-enhanced CT, to investigate suspected recurrence. Diagnostic performance of PET/contrast-enhanced CT (PET/ceCT), PET/non-contrast-enhanced CT (PET/ncCT) and contrast-enhanced CT (ceCT) for local or regional recurrence, distant metastasis, overall recurrence and second primary cancer was evaluated. The reference standard included histopathology, treatment change and imaging follow-up.Results: The patient-based areas under the receiver operating characteristic curves (AUC) for ceCT, PET/ncCT and PET/ceCT were 0.82, 0.96 and 0.98 for local recurrence, 0.73, 0.86 and 0.86 for regional recurrence, 0.86, 0.91 and 0.92 for distant metastasis, 0.72, 0.86 and 0.87 for overall recurrence, and 0.86, 0.89 and 0.91 for a second primary cancer. Both PET/ceCT and PET/ncCT statistically showed larger AUC than ceCT for recurrence, and the difference between PET/ceCT and PET/ncCT for local recurrence reached a significant level (p = 0.039). The accuracy of PET/ceCT for diagnosing overall recurrence was high, irrespective of the time interval after the last treatment (83.3-94.1 %).Conclusion: FDG-PET/CT was a more accurate HNSCC restaging tool than ceCT. The added value of ceCT at FDG-PET/CT is minimal.Key Points: • FDG-PET/CT is a more accurate post-treatment surveillance tool than ceCT for HNSCC. • FDG-PET/ceCT was useful, irrespective of the time interval after the last treatment. • FDG-PET/ceCT showed high negative predictive value and limited positive predictive value. • The added value of ceCT at FDG-PET/CT is minimal and likely not clinically relevant. [ABSTRACT FROM AUTHOR]

Brain Positron Emission Tomography/Computed Tomography with F-fluorodeoxyglucose (FDG PET/CT) was performed in a 44-year-old woman with marked cognitive impairment, diffuse myalgias, sensory, memory and visual disorders, and chronic fatigue, presenting with histopathological features of macrophagic myofasciitis (MMF) at deltoid muscle biopsy. Cerebromedullary Magnetic Resonance Imaging (MRI), electromyography, ophthalmic examination, and cerebrospinal fluid analysis were normal. Visual analysis of FDG PET/CT images showed an atypical pattern of hypometabolism, involving symmetrically the occipital cortex, temporal lobes, and limbic system (including in particular amygdalo-hippocampal complexes), and the cerebellum. Posterior cingulate cortex and parietal areas were preserved. This pattern was confirmed by a voxel-based procedure using Statistical Parametric Mapping (SPM12) that compared a patient's images to normal reference samples from six healthy subjects with adjustment to age obtained using the same PET/CT camera. These results provide a glucose metabolism substrate for cognitive complaints in patients with long-lasting aluminium hydroxide-induced MMF. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the diagnostic and prognostic value of (18)F-FDG-PET/CT for axillary lymph node (LN) staging in breast cancer patients, employing histologic evaluation as the reference.Methods: Among 196 patients with biopsy-proven breast cancer who had undergone (18)F-FDG-PET/CT before mastectomy or breast-conserving surgery with sentinel LN biopsy and/or axillary LN dissection, 200 axillae were retrospectively analyzed by visual assessment and quantitatively using SUVmax. LN SUVmax as well as other clinicopathological features were assessed for their prognostic value using the log-rank test and Cox method.Results: Metastasis was diagnosed histopathologically in 56 (28 %) axillae. The sensitivity, specificity, and accuracy of visual PET/CT for diagnosing node metastasis were 55.4, 95.8, and 84.5 %, respectively. When the optimal discriminative SUVmax cutoff was 1.5, these figures were 51.8, 97.2, and 84.5 %, respectively. Fourteen of 55 patients (25.5 %) with LN metastases suffered a recurrence during follow-up (median 39 months). Patients with a high nodal SUVmax (≥1.7) had a significantly lower progression-free survival rate than those with a low SUVmax (p = 0.0499). Axillary nodal and primary tumor SUVmax as well as estrogen receptor status were significantly associated with recurrence.Conclusion: Axillary nodal SUVmax may be a prognostic indicator of disease recurrence in patients with axillary LN metastases. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate in 18 patients with ischaemic stroke classified as cryptogenic and presenting non-stenotic carotid atherosclerotic plaques the morphological and biological aspects of these plaques with magnetic resonance imaging (MRI) and F-fluoro-deoxyglucose positron emission tomography (F-FDG PET) imaging. Methods: Carotid arteries were imaged 150 min after injection of F-FDG with a combined PET/MRI system. American Heart Association (AHA) lesion type and plaque composition were determined on consecutive MRI axial sections ( n = 460) in both carotid arteries. F-FDG uptake in carotid arteries was quantified using tissue to background ratio (TBR) on corresponding PET sections. Results: The prevalence of complicated atherosclerotic plaques (AHA lesion type VI) detected with high-resolution MRI was significantly higher in the carotid artery ipsilateral to the ischaemic stroke as compared to the contralateral side (39 vs 0 %; p = 0.001). For all other AHA lesion types, no significant differences were found between ipsilateral and contralateral sides. In addition, atherosclerotic plaques classified as high-risk lesions with MRI (AHA lesion type VI) were associated with higher F-FDG uptake in comparison with other AHA lesions (TBR = 3.43 ± 1.13 vs 2.41 ± 0.84, respectively; p < 0.001). Furthermore, patients presenting at least one complicated lesion (AHA lesion type VI) with MRI showed significantly higher F-FDG uptake in both carotid arteries (ipsilateral and contralateral to the stroke) in comparison with carotid arteries of patients showing no complicated lesion with MRI (mean TBR = 3.18 ± 1.26 and 2.80 ± 0.94 vs 2.19 ± 0.57, respectively; p < 0.05) in favour of a diffuse inflammatory process along both carotid arteries associated with complicated plaques. Conclusion: Morphological and biological features of high-risk plaques can be detected with F-FDG PET/MRI in non-stenotic atherosclerotic plaques ipsilateral to the stroke, suggesting a causal role for these plaques in stroke. Combined F-FDG PET/MRI systems might help in the evaluation of patients with ischaemic stroke classified as cryptogenic. [ABSTRACT FROM AUTHOR]

Objective: Modern PET/CT scanners have significantly improved detectors and fast time-of-flight (TOF) performance and this may improve clinical performance. The aim of this study was to analyze the impact of a current generation TOF PET/CT scanner on standardized uptake values (SUV), lesion-background contrast and characterization of the adrenal glands in patients with suspected lung cancer, in comparison with literature data and commonly used SUV cut-off levels.Methods: We included 149 adrenal glands from 88 patients with suspected lung cancer, who underwent (18)F-FDG PET/CT. We measured the SUVmax in the adrenal gland and compared this with liver SUVmean to calculate the adrenal-to-liver ratio (AL ratio). Results were compared with literature derived with older scanners, with SUVmax values of 1.0 and 1.8 for normal glands [1, 2]. Final diagnosis was based on histological proof or follow-up imaging. We proposed cut-off values for optimal separation of benign from malignant glands.Results: In 127 benign and 22 malignant adrenal glands, SUVmax values were 2.3 ± 0.7 (mean ± SD) and 7.8 ± 3.2 respectively (p < 0.01). Corresponding AL ratios were 1.0 ± 0.3 and 3.5 ± 1.4 respectively (p < 0.01). With a SUVmax cut-off value of 3.7, 96% sensitivity and 96% specificity was reached. An AL ratio cut-off value of 1.8 resulted in 91% sensitivity and 97% specificity. The ability of both SUVmax and AL ratio to separate benign from malignant glands was similar (AUC 0.989 vs. 0.993, p = 0.22).Conclusions: Compared with literature based on the previous generation of PET scanners, current generation TOF (18)F-FDG PET/CT imaging provides higher SUVs for benign adrenal glands, while it maintains a highly accurate distinction between benign and malignant glands. Clinical implementation of current generation TOF PET/CT requires not only the use of higher cut-off levels but also visual adaptation by PET readers. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to optimize image reconstruction conditions for brain (18)F-FDG, (11)C-PiB, (18)F-florbetapir and (18)F-flutemetamol PET imaging with Discovery-690 PET/CT for diagnosis and research on Alzheimer's disease (AD) based on the standard imaging protocols and phantom test procedures and criteria published by the Japanese society of nuclear medicine (JSNM).Methods: A Hoffman 3D brain phantom and a cylindrical pool phantom were scanned according to the JSNM procedure, and the reconstruction conditions (iteration, subset, post-filter) were optimized so that the images satisfy the JSNM criteria regarding spatial resolution (FWHM ≤ 8 mm) and gray/white matter contrast (%contrast ≥ 55%) on the Hoffman phantom and uniformity (SD of small ROIs ≤ 0.0249) and image noise (coefficient of variation ≤ 15 %) on the pool phantom. Human images were acquired with (18)F-FDG (15-min scan starting at 30 min post-injection [p.i.] of 185 MBq), (11)C-PiB (20-min scan starting at 50 min p.i. of 555 MBq), (18)F-florbetapir (10-min scan starting at 50 min p.i. of 370 MBq) and (18)F-flutemetamol (30-min scan starting at 90 min p.i. of 185 MBq) on 1 or 2 subjects for each tracer and reconstructed with thus determined conditions to evaluate the image quality visually. The effect of reconstruction parameters on the standardized uptake value ratio (SUVR) was also evaluated on 5 amyloid-positive and 5 amyloid-negative PiB images.Results: A sufficient image quality was obtained at an iterative update (product of iteration and subset) of 64 for (18)F-FDG. The same reconstruction parameters with an additional Gaussian filter of 5 mm FWHM was optimal for (11)C-PiB, (18)F-florbetapir and (18)F-flutemetamol to achieve the phantom criteria. Those optimal reconstruction conditions were confirmed with human images. The SUVR value was stable over a wide range of iterative updates around the optimal parameters both for positive and negative amyloid images.Conclusions: Optimal image reconstruction conditions were determined for brain (18)F-FDG and amyloid PET imaging with Discovery-690 PET/CT for diagnosis and research on AD based on the JSNM phantom criteria. This supports feasibility of the phantom criteria for standardization and harmonization of brain (18)F-FDG and amyloid PET for multicenter studies. [ABSTRACT FROM AUTHOR]

Objective: We retrospectively investigated changes of (18)F-fluorodeocyglucose ((18)F-FDG) uptake in the spinal cord, inside and outside the radiation fields, in patients with esophageal cancer before and after conventional dose radiotherapy.Methods: A total of 17 consecutive patients with esophageal cancer (16 males, one female; age 50-83 years, mean 67.0 years), who underwent conventional dose radiotherapy and (18)F-FDG PET/CT before and 5.1 months (range 1.6-8.6 months) after the radiotherapy, were retrospectively evaluated. Sixteen patients had esophageal cancer and one patient had esophageal metastasis from thyroid cancer. Mean standardized uptake values (SUVmean) of the cervical, thoracic (inside and outside the radiation fields) and lumbar spinal cord were measured.Results: SUVmean of the thoracic spinal cord inside the radiation field was decreased significantly after radiotherapy compared to those before radiotherapy (p < 0.001). SUVmean of the cervical spinal cord showed the same trend but it was not statistically significant (p = 0.051). SUVmean of the thoracic spinal cord outside the radiation field and the lumbar spinal cord did not differ significantly before and after the radiotherapy (p = 0.146 and p = 0.701, respectively).Conclusions: The results suggest that glucose metabolism of the spinal cord is decreased in esophageal cancer patients after conventional dose radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to give an overview of studies investigating the role of fludeoxyglucose F18 (F-FDG) positron emission tomography (PET) scanning in patients with aortic aneurysms with a focus on molecular characteristics of the aneurysm wall. Methods: MEDLINE, EMBASE, and the Cochrane database were searched for relevant articles. After inclusion and exclusion, we selected 18 relevant articles reporting on F-FDG PET scanning of aortic aneurysms. Results: The sample size of studies is limited, and there are no standardized imaging protocols and quantification methods. F-FDG PET scanning was shown to display molecular characteristics of the aortic wall. Different studies showed contradictory findings of aortic F-FDG uptake in aneurysm patients compared to controls. Conclusions: Non-invasively determining molecular characteristics of aortic wall weakening might lead to better rupture and growth prediction. This might influence the decision of the surgeon between conservative and surgical treatment of aneurysms. To date, there is conflicted evidence regarding the use of F-FDG PET scanning to predict aneurysm rupture and growth. The role of F-FDG PET scanning in rupture risk prediction needs to be further investigated, and standardized imaging protocols and quantification methods need to be implemented. [ABSTRACT FROM AUTHOR]