Standardized Uptake Value Levels Research Articles

Combined Metabolic and Functional Tumor Volumes on [18F]FDG-PET/MRI in Neuroblastoma Using Voxel-Wise Analysis.

The purpose of our study was to evaluate the association between the [18F]FDG standard uptake value (SUV) and the apparent diffusion coefficient (ADC) in neuroblastoma (NB) by voxel-wise analysis. From our prospective observational PET/MRI study, a subcohort of patients diagnosed with NB with both baseline imaging and post-chemotherapy imaging was further investigated. After registration and tumor segmentation, metabolic and functional tumor volumes were calculated from the ADC and SUV values using dedicated software allowing for voxel-wise analysis. Under the mean of thresholds, each voxel was assigned to one of three virtual tissue groups: highly vital (v) (low ADC and high SUV), possibly low vital (lv) (high ADC and low SUV), and equivocal (e) with high ADC and high SUV or low ADC and low SUV. Moreover, three clusters were generated from the total tumor volumes using the method of multiple Gaussian distributions. The Pearson's correlation coefficient between the ADC and the SUV was calculated for each group. Out of 43 PET/MRIs in 21 patients with NB, 16 MRIs in 8 patients met the inclusion criteria (PET/MRIs before and after chemotherapy). The proportion of tumor volumes were 26%, 36%, and 38% (v, lv, e) at baseline, 0.03%, 66%, and 34% after treatment in patients with response, and 42%, 25%, and 33% with progressive disease, respectively. In all clusters, the ADC and the SUV correlated negatively. In the cluster that corresponded to highly vital tissue, the ADC and the SUV showed a moderate negative correlation before treatment (R = -0.18; p < 0.0001) and the strongest negative correlation after treatment (R = -0.45; p < 0.0001). Interestingly, only patients with progression (n = 2) under therapy had a relevant part in this cluster post-treatment. Our results indicate that voxel-wise analysis of the ADC and the SUV is feasible and can quantify the different quality of tissue in neuroblastic tumors. Monitoring ADCs as well as SUV levels can quantify tumor dynamics during therapy.

Prognostic Factors in Lung Adenocarcinoma with Brain Metastasis

Introduction: Brain metastasis (BM) is significantly seen in lung adenocarcinoma and adversely affects survival. We aimed to evaluate the factors affecting the prognosis in patients with BM diagnosed with lung adenocarcinoma. Materials and Methods: Patients with BM between 2012 and 2022 were reviewed retrospectively. Demographic characteristics of the patients, primary tumor characteristics, presence of mutation, BM number, localization, size, development time, and treatment characteristics were evaluated. Inflammatory indices at the time of BM were examined. The overall survival time was calculated. Results: About 92.9% of 113 patients were male, the median age was 62 years (54.5–68.5), and follow-up was 8 months (3–18). BM was detected at the time of diagnosis in 62 (54.9%) of the patients, whereas BM developed later in 51 (45.1%) patients. Systemic treatment was applied to 72.5% of the patients. Survival was lower in patients with BM at diagnosis (4 vs. 14 months, P &lt; 0.001). Primary tumor maximum standardized uptake value level was higher on fluorodeoxyglucose-positron emission tomography-computed tomography at diagnosis in patients with late BM (P = 0.004). The development time of BM was 9 months (4–16), and the median survival was 8 months (6.2–9.8). There was no difference between tumor localization or inflammatory indices and the development of BM and prognosis. The presence of BM at diagnosis and lack of systemic treatment were found to be factors that independently reduced survival (P &lt; 0.001, P = 0.007). Conclusion: The presence of BM at diagnosis significantly reduces survival. It has been observed that systemic treatments applied in addition to local treatments have a positive effect on the prognosis.

Диагностические возможности ПЭТ/КТ с 18F-ПСМА у пациентов с подозрением на рак предстательной железы

Relevance. Prostate cancer (PC) is one of the most common malignant neoplasms in men. Every year, about 1.4 million new cases of prostate cancer are diagnosed in the world and 366,000 men die each year from this pathology. Despite the presence of a fairly wide range of diagnostic options in the early diagnosis of prostate cancer, primarily the determination of the level of prostate specific antigen (PSA) in the blood serum and multiparametric magnetic resonance imaging (mpMRI), there remains a group of patients with ambiguous values of the above indicators. The use of positron emission tomography combined with computed tomography (PET/CT) with a tumoritropic radiopharmaceutical drug (RFLP) 18F-PSMA improves the early diagnosis of prostate cancer, which is the key to success for successful treatment, duration and quality of life of the patient. Material and methods. The study included 30 patients with suspected prostate cancer, based on the PSA level in the ʽgray zoneʼ 2–10 ng/ml and Pi-RADS 3 according to the MRI data. All patients underwent PET/CT with 18F-PSMA, with further morphological verification of the process. Results. Out of 30 patients, 7 (23.33%) had positive PET/CT with 18F-PSMA. The diagnostic model obtained during the construction and subsequent analysis of the SUV level ROC-curve showed high values of sensitivity (86%), specificity (100%), diagnostic accuracy (86%) and positive predictive value (100%) of the method (area under ROC-curve (AUC) 0.93), with reference indicators of RFLP accumulation – standardized uptake value (SUV) 2.5. The negative predictive value was 27%. Conclusion. Our study confirmed the high diagnostic accuracy of PET/CT with 18F-PSMA in the differential diagnosis of a tumor process in the prostate gland, with a reference indicator SUV &gt; 2.5. We recommend 18F-PSMA PET/CT in patients with suspected PCa who have ambiguous PSA (2-10 ng/mL) and mpMRI (Pi-RADS 3) findings.

Can Radiomics Analyses in 18F-FDG PET/CT Images of Primary Breast Carcinoma Predict Hormone Receptor Status?

Objectives:This study aimed to investigate the role of preoperative 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) radiomics features and metabolic parameters of primary breast tumors in predicting hormone receptor (HR) positivity.Methods:A total of 153 patients with breast carcinoma who underwent preoperative 18F-FDG PET/CT were included. All PET/CT images were retrospectively reevaluated. Radiomics features of primary breast lesions reflecting tumor heterogeneity as well as standardized uptake value (SUV) metrics (SUVmin, SUVmean, SUVmax, and SUVpeak) and volumetric parameters such as metabolic tumor volume and total lesion glycolysis (TLG) were extracted by commercial texture analysis software package (LIFEx; https://www.lifexsoft.org/ index.php). WEKA and SPSS were used for statistical analysis. Binary logistic regression analysis was used to determine texture features predicting HR positivity. Accuracy, F-measure, precision, recall, and precision-recall curve area were used as data-mining performance criteria of texture features to predict HR positivity.Results:None of the radiomics parameters were significant in predicting HR status. Only SUV metrics and TLG were statistically important. Mean ± standard deviations for SUVmean, SUVmax, and SUVpeak for the HR-negative group were significantly higher than those in the HR-positive group (6.73±4.36 vs. 5.20±3.32, p=0.027; 11.55±7.42 vs. 8.63±5.23, p=0.006; and 8.37±6.81 vs. 5.72±4.86; p=0.012). Cut-off values of SUVmean, SUVmax, and SUVpeak for the prediction of HR positivity were 4.93, 8.35, and 6.02, respectively. Among data-mining methods, logistic regression showed the best performance with accuracy of 0.762.Conclusion:In addition to the relatively limited number of patients in this study, radiomics parameters cannot predict the HR status of primary breast cancer. SUV levels of the HR-negative group were significantly higher than those of the HR-positive group. To clarify the role of metabolic and radiomics parameters in predicting HR status in breast cancer, further studies involving a larger study population are needed.

PET-CT Invisible Diffuse Large B-Cell Lymphoma Features a Silent B-Cell Receptor Signaling

Background:18F-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET-CT) has been widely used in lymphoma patients for diagnosis, staging, assessment of response and surveillance. And the standardized uptake value (SUV), a commonly used indicator in PET-CT scan, can quantitatively reflect the glucose uptake and glycolysis of the tumor. Diffuse large B-cell lymphoma (DLBCL), one of the most common subtypes of aggressive lymphomas, is supposed to exhibit high standardized uptake value (SUV) in 18F-FDG PET-CT due to high rate of glucose (18F-FDG) uptake and high level of glycolysis. Nevertheless, PET-CT “invisible” DLBCL cases have also been described, which featuring a relatively low 18F-FDG uptake denoted by low SUV. Herein, we analyzed this subgroup of under-estimated disease.Methods: Nineteen cases each with PET-CT “invisible” (PET-CTi) and PET-CT “visible” (PET-CTv) de novo DLBCL were submitted for an immunohistochemical detection for the expression level of B-cell receptor (BCR) signaling-related molecules. Nine xenografts derived from BCR-dependent and BCR-independent DLBCL cell lines were further submitted for a small animal 18F-FDG PET-CT scanning and the following immunohistochemical detection for BCR signaling-related molecules.Results: The immunohistochemical expression level of pSYK (pY525/526), a key effector molecule for BCR signaling, was significantly lower in PET-CTi DLBCL tumor tissues compared with that in PET-CTv DLBCL cases (P <0.01). With regard to in vivo PET-CT experiment, the xenografts derived from BCR-independent DLBCL cell lines exhibited remarkable lower SUV level than those derived from BCR-dependent cell lines (P < 0.01). And BCR-independent DLBCL xenografts featured relatively lower expression level of pSYK compared with those BCR-dependent ones (P <0.01).Conclusions:18F-FDG PET-CT negative DLBCL features a silent BCR signaling and 18F-FDG PET-CT may be of use in evaluating BCR signaling status. DisclosuresNo relevant conflicts of interest to declare.

Correlations of 68Ga-PSMA PET/CT in the initial staging of prostate cancer patients.

The aim of this study was to evaluate the correlations between the different risk groups of prostate cancer (PCa) regarding the presence of metastasis and the gallium-68 prostate specific membrane antigen (68Ga-PSMA) uptake patterns in the prostate gland. One hundred thirty nine patients with newly diagnosed, untreated PCa who underwent 68Ga-PSMA PET/CT imaging for staging between July 2017 and March 2019 were enrolled in this retrospective study. Maximum standardized uptake values (SUVmax) were determined by manually placing the region of interest to the primary tumor in the prostate gland. Patients were divided into groups according to their prostate-specific antigen (PSA) values, International Society of Urological Pathology (ISUP) grade groups, Gleason Scores (GS), D'Amico risk stratification criteria and the presence of metastasis. Mann Whitney U test was used in the comparison of two groups of data. In multivariate analysis, logistic regression was used to determine independent predictors for the presence of metastasis. There were statistically significant differences between D'Amico risk groups in terms of prostate SUVmax levels. The SUVmax levels of the patients in the high risk group were significantly higher than the SUVmax levels of the patients in the low-medium risk groups (P<0.001). Maximum standardized uptake value levels of the patients with PSA level 20ng/mL and above were significantly higher than those with PSA level below 20ng/mL (P<0.001). The metastatic rate of patients with 68Ga-PSMA uptake on two lobes of the prostate gland was significantly higher (42.6%) than the metastatic rate of patients with 68Ga-PSMA uptake on only one lobe (7.9%) (P<0.001).The median SUVmax of tumours in patients with metastasis was statistically significantly higher than in patients with no metastasis. In multivariate analysis; bilobar involvement, PSA value 20ng/mL, prostate SUVmax value 8.6 and GS 8 were determined as independent predictors for the presence of metastasis. The strong correlation between PSA values and/or Gleason score/Grade and SUVmax values suggests that the SUVmax value of the prostate gland might be a valuable determinant in risk classifications.

ARVC specific autoantibody identifies cardiac sarcoidosis and correlates with inflammation activity

Abstract Introduction Cardiac sarcoidosis (CS) is an inflammatory granulomatous disease of unknown origin. CS and arrhythmogenic right ventricular cardiomyopathy (ARVC) are overlapping syndromes. With both, patients are at increased risk of ventricular arrhythmias and sudden cardiac death. However, the diagnosis of CS is challenging, especially in patients with no extracardiac involvement, but correct diagnosis has large therapeutic impact. Recently, a novel diagnostic autoantibody (anti-DSG2 Ab) was identified in ARVC. We sought to identify this antibody in CS patients and correlate its levels with inflammation activity using cardiac positron-emission-tomography (18-FDG-PET). Methods Recombinant human desmoglein-2 (DSG2) proteins on western blots were exposed to sera as well as purified IgG of 14 patients with sarcoidosis (all confirmed by histology) and 6 controls (1 ARVC patient (positive control) and 5 healthy control subjects (negative control)). Clinical patient characteristics were correlated to detected antibody intensity levels. Results The sarcoidosis cohort comprised 43% (6/14) male patients and the average age was 50±12 years. Anti-DSG2 Abs were identified in 43% (6/14) and were detected faintly (below cut off level) in 21% (3/14) of all sarcoidosis patients. Antibody was also present in the ARVC patient (1/1) and was absent in all control subjects (5/5). Myocardial inflammation was present in 18-FDG PET imaging in all CS patients with positive anti-DSG2 Abs, corresponding to an average SUV (standardized uptake value) of 8.1±4.2. In patients with faint or no antibody, the SUV values were significantly lower with 1.2±2.1 and 3.2±4.0, respectively (P=0.044, one-way ANOVA). The Pearson correlation coefficient (R) was 0.6 (P=0.037) for SUV vs. higher antibody levels assessed by pixel count of the western blot bands for purified IgG. Conclusions Anti-DSG2 Abs are not only a specific biomarker for ARVC, but are also found in CS, suggesting a similar pathophysiological mechanism in these overlapping syndromes, both involving cardiac inflammation and myocyte cell death. Moreover, antibody levels correlate with disease activity on cardiac PET imaging. Larger cohorts are necessary to confirm these findings. Funding Acknowledgement Type of funding source: None

Spinal cord hypometabolism associated with infection by human T-cell lymphotropic virus type 1(HTLV-1).

BackgroundHTLV-1 infection is endemic in Brazil. About 1 to 2% of the Brazilian population is estimated to be infected, but most infected HTLV-1 individuals do not know about their own infection, which favors the continuity of sexual and vertical virus transmission. In addition, HTLV-1 associated central nervous system diseases and their pathophysiologic mechanisms are not fully understood. This study aimed to evaluate the correlation of spinal cord metabolism, viral and inflammatory profiles with features of neurological presentation in HTLV-1 infected individuals.MethodologyThis is a cross-sectional study of a cohort including 48 HTLV-1 infected individuals clinically classified as asymptomatic-AG (N = 21), symptomatic-SG (N = 11) and HAM/TSP-HG (N = 16) and a nested case-control study with HTLV-1 infected individuals-HIG (N = 48) and HTLV-1 non infected controls-CG (N = 30) that had their spinal cord analysed by Positron Emission Tomography with 18F-Fluordeoxyglucose (18F-FDG PET/CT). HTLV-1 infected individuals had 18F-FDG PET/CT results analyzed with clinical and demographic data, proviral load, cytokines and chemokines in the blood and cerebrospinal fluid (CSF).Principal Findings18F-FDG PET/CT showed hypometabolism in the thoracic spinal cord in HTLV-1 infected individuals. The method had an accuracy of 94.4% to identify HAM/TSP. A greater involvement of the thoracic spinal cord was observed, although hypometabolism was also observed in the cervical spinal cord segment in HTLV-1 infected individuals. Individuals with HAM/TSP showed a pro-inflammatory profile in comparison to asymptomatic and symptomatic groups, with a higher level of Interferon-inducible T-cell alpha chemoattractant (ITAC/CXCL11), IL-6, IL-12p70 in the plasma; and ITAC, IL-4, IL-5, IL-8 (CXCL8) and TNF-alpha in the CSF. Using regression, thoracic spinal cord SUV (standardized uptake value) and CSF ITAC level were identified as the HAM/TSP predictors in the multivariate model.Conclusions18F-FDG PET/CT imaging showed spinal cord hypometabolism in most HTLV-1 infected individuals, even in the asymptomatic HTLV-1 group. Thoracic spinal cord hypometabolism and CSF-ITAC levels were identified predictors of HAM/TSP.SignificanceOur findings suggested that in most HTLV-1 infected individuals there was compromise of central nervous system (CNS) structures despite of the lack of clinical symptoms. To explain the found hypometabolism, the role of microcirculatory and metabolic factors in the pathogenesis of neurological diseases associated with HTLV-1 infection must be further investigated. It is paramount to evaluate the central nervous function and to compare the performance among HTLV-1 infected individuals considered asymptomatic to the uninfected controls.

Pulmonary sequestration associated with increased serum tumor markers and elevated standard uptake value level in PET/CT

Rationale:Pulmonary sequestration (PS) is a congenital pulmonary malformation wherein a piece of tissue that ultimately develops into lung tissue is not attached to the pulmonary arterial blood supply, sometimes it is difficult to diagnosis with no specific laboratory tests, discover an abnormal blood supply from aorta by imaging tests is a key step in diagnose.Patient concerns:A 54-year-old male smoker presented with cough, expectoration and blood in the sputum.Diagnoses:Computed tomography (CT) shows lesion in right lung, moderate standard uptake value (SUV) elevation of position-emission tomography/computed tomography (PET/CT) in a part of the lesion, and an increased (1,3)-β-D-glucan assay (G test), Galactomannan enzyme immune-assay (GM test) and tumor marker level, biopsy of lung in different times produced inconclusive results, then finally diagnose of pulmonary sequestration is made by observing an abnormal blood supply from the thoracic aorta and volume change of mass.Interventions:The patient refused lower lobectomy which is the main treatment of PS. He was discharged with oral hemostatic and was advised to undergo regular medical checkups.Outcomes:The patient has been followed for a year under an outpatient regimen. Symptoms of the cough and expectoration were relieved, however, blood in the sputum remains unchanged.Lessons:It suggests the need for criteria for a thorough diagnostic work-up. It put emphasis on the importance of considering PS as part of the diagnosis of a lesion in the lung disease and underscore the blood supply of mass. Bronchoscopy or pulmonary lobectomy and follow up of the patient are important for patients diagnosed with pulmonary sequestration.

Concurrent benign metastasizing leiomyoma in the lung and lumbar spine with elevated standardized uptake value level in positron-emission tomography computed tomography

Rationale:Benign metastasizing leiomyoma (BML) is rare condition involving distant metastases secondary to benign uterine leiomyoma, and it is most commonly found in the lungs. It rarely metastasizes to the spine to cause osteolytic damage and spinal canal compression.Patient concerns:A 51-year-old woman with low back and bilateral leg pain and paresthesia was admitted to our ward. She has a previous medical history of uterine leiomyomas. Magnetic resonance imaging of the lumbar spine revealed vertebral body osteolytic destruction and soft tissue mass in the L4/5 with a secondary lumbar spinal stenosis. Positron emission tomography computed tomography showed moderately intense accumulation of 18F-fluorodeoxyglucose in the L4/5 mass, as well as multiple nodules with increased metabolic activity in both lungs.Diagnoses:Pulmonary and spinal BML.Interventions:The patient underwent a computed tomography-guided percutaneous needle biopsy of the lung nodule and lumbar corpectomy, tumor excision, and vertebroplasty in the L4/5.Outcomes:Pathologically, both pulmonary nodule and vertebral mass were diagnosed as leiomyomas without any malignant evidence. Estrogen and progesterone receptors were both positive in the metastatic tumors. The patient's symptoms completely disappeared after the surgery. The patient is currently receiving outpatient anti-estrogen tamoxifen treatment for a BML.Lessons:Through this case, we suggest that BML should be regarded as part of differential diagnosis in female patients with a previous medical history of uterine leiomyomas presenting with multiple nodules in any parts of the body.

P1.03-027 Clinical and Histological Features Associated with SUV in FDG-PET-CT in Patients with Adenocarcinoma of the Lung

FDG-PET-CT is increasingly used for staging and treatment monitoring in NSCLC. The prognostic and possibly predictive value of the standardized-uptake-value (SUV), and the clinical, molecular and pathological features contributing to SUV levels have not been well described. We retrospectively reviewed the records of patients staged with FDG-PET-CT and correlated SUV values before and during treatment with clinical and pathological features of the tumor including CRP as a marker of systemic inflammation, adenocarcinoma subtype (solid, lepidic etc.), and Ki67, as a marker of tumor proliferation. 190 patients with adenocarcinoma of the lung were identified. 110 had FDG-PET-CT staging and were included in this analysis. Tumor subtypes were as follows: 50.0% solid, 16.4% acinar, 9.1% papillary, 7.3% lepidic, 1.8% micropapillary, 15.4% other. 70 patients received systemic treatment and 40 were treated surgically. The mean primary-tumor-SUV for all patients was 11.1 (for patients treated medically, 13.5, and for those treated surgically, 8.6). Ki67 expression in the tumor was lowest in the group with SUV < 10 (38.6%) and highest in the group with SUV > 20 (56.0). The group with SUV 11-19 had a moderate Ki67 expression (47.9%). In patients with surgical tumor samples there was a trend towards higher SUV in patients with tumors showing 30% or more solid growth pattern (mean SUV 11.4) and lower SUV in patients with any lepidic growth (mean SUV 4.0) (p=0.002). Systemic markers of inflammation were significantly higher in patients whose tumors had SUV>10 (mean CRP, 2.3 mg/dl; mean leukocytes, 9.7 G/L) than in patients with low-SUV tumors (<5) (mean CRP, 0.4 mg/dl, p=0.0186; mean leukocytes, 7.2 G/L, p=0.014). Multiple factors appear to be associated with higher or lower SUV values, including adenocarcinoma subtype, proliferation index of the tumor and systemic inflammation. These factors should be taken into account when interpreting FDG-PET-CT SUV values in clinical practice. The correlation of FDG-PET-CT SUV values with inflamed tumor phenotypes, and the possible predictive value of SUV for response to immune therapies, should be further investigated.

Abstract A47: Membrane translocation of GLUT1 induced by TP53 mutation is positively correlated with increased glucose uptake in patients with breast cancer

Abstract Background: High rate of glycolysis exhibited by cancer cells plays a crucial role in carcinogenesis and tumor progression. To uncover candidate contributing to increasing glucose uptake in breast cancer, we interrogated clinical transcriptome data set from 66 patients undergoing preoperative 18F-fluorodeoxy glucose positron emission tomography (FDG-PET). Also, we validated the candidate in other clinical data and confirm its role in glucose uptake through cell line works. Methods: Clustered analysis by standardized uptake value (SUV) from FDG-PET and gene network analysis suggested that repression of p53 might be a key molecule associated with elevated SUV level. To validate p53 as a major determinant in an elevated glucose uptake, we used second cohort consisted of women with p53 gene sequencing analysis and FDG-PET. Mutational analysis of exons 5-9 of the p53 gene was carried out using polymerase chain reaction-denaturing high performance liquid chromatography. Of these women, to reduce bias and clearly estimate the influence of p53 mutation on SUV and survival, we identified 114 women by propensity-score matching method. Next, among the molecules associated glucose uptake, we compared the expression of GLUT1 using tissue-microarray (TMA). The TMA was constructed using achievable 73 tumors from second cohort with case-matching by P53 mutation status. Then, we validated the role of P53 in glucose uptake by mammary cell using the experiments with MCF-10A cell line. To compare the degree of glucose uptake between P53-mutated and P53-intact cells, we measured gamma activities of these cell lines after treated with 18F-FDG media. Simultaneously, different amount of glucose uptake is visualized using the PET camera. Results: In case-matched cohort by P53 status, the mean SUV of p53-mutational group was significantly higher than that of wild-type p53-group (7.49 vs. 5.44, P=0.013). Compared with the group with intact p53, recurrence-free survival (RFS) was significantly reduced in the group with p53 mutation (P =0.017). In multivariate analysis, p53 mutational status carried prognostic significance (hazard ratio 3.73, 95% CI 1.15-12.07) independent of tumor size, nodal status, and estrogen receptor status. In immunohistochemical stain with GLUT1 using the TMA, we found that the expression of membraneous GLUT1 was significantly higher in P53-mutated tumors than in P53-intact tumor (P=0.022), in support of previous finding showing that P53 mutation promotes GLUT1 translocation to cell membrane. In experiments with MCF10A cell lines, we found that gamma activities and signal intensity by the absorption of18F-glucose were much higher in P53-mutated cell than in P53-intact cell. These experiments showed that the amount of glucose uptake in mammary cell increases followed by P53 mutation, supporting our clinical findings. Conclusion: We showed that TP53 mutation promotes GLUT1 translocation to membrane, which consequently induces glucose influx in patients with breast cancer. In terms of glucose metabolism, P53 mutation caused the increase of glucose uptake within tumor and adversely affect survival in breast cancer. Citation Format: Sung Gwe Ahn, Hak Woo Lee, Airi Han, Jeong Joon. Membrane translocation of GLUT1 induced by TP53 mutation is positively correlated with increased glucose uptake in patients with breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A47.

Abstract 1486: Fatty acid and phospholipid profiling of liver tumor tissue: correlation with in vivo molecular PET imaging of phosphocholine synthesis

Abstract Alterations in phospholipid and fatty acid metabolism may play key roles in hepatocarcinogenesis. Phosphocholine synthesis can be imaged and quantified in-vivo by positron emission tomography (PET) using radiopharmaceuticals bearing the choline moiety. Results from this PET assessment of tissue phospholipid metabolism were compared to phospholipid and fatty acid profiles of both tumor and liver parenchymal tissues in patients with liver cancer undergoing hepatectomy. Fluorine-18 fluorocholine PET/CT of the liver was completed &amp;lt;2 weeks prior to surgery as part of a clinicaltrials.gov-registered (NCT01395030) IRB-approved clinical study with written informed consent. Paired tumor and parenchymal tissue samples were collected in liquid nitrogen (20 hepatocellular carcinoma, 3 with intrahepatic cholangiocarcinoma), freeze-dried, homogenized and extracted with methanol/CHCl3/water containing BHT as preservative. The organic phase was analyzed by orbitrap LCMS after electrospray ionization in positive mode to quantify fatty acids (after derivatization) and phospholipid metabolites. Tumor and liver standardized uptake value (SUV) measurements were obtained from static PET images. Tumors exhibited significantly lower levels of docosahexaenoic acid, docasopentanoic acid, alpha-linolenic acid and significantly higher levels of palmitoleic acid, eicosadienoic acid, arachadonic acid, and linoleic acid than peritumoral liver tissue. Tumors also exhibited significantly higher SUVs than surrounding liver. Highest tumor SUV correlated significantly with tumor levels of palmitoleic acid, gamma linolenic acid, CDP choline, phosphatidylcholine, phosphatidylethanolamine and phosphatidylinsolitol. In contrast, no significant correlations were noted between tumor SUV and peri-tumoral levels of these compounds. Peritumoral liver SUV was significantly correlated with levels of myristic acid, eicosaptaenoic acid, gamma-linolenic acid, palmitoleic acid, docosapentaenoic acid, linoleic acid, oleic acid, and palmitic acid in peritumoral liver tissue. Furthermore, parenchymal liver SUV was inversely correlated with the Knodell histologic activity index (HAI), as well as histologic features of portal inflammation, piecemeal necrosis, and fibrosis. These histology features were also inversely correlated with liver tissue concentrations of docosahexaenoic acid, CDP-choline, total phosphaticylcholine, and total phosphatidylinositol. No significant correlations were found between tumor fatty acid/phospholipid levels and Edmonson-Steiner tumor grade. These preliminary results may indicate multiple inter-related metabolic alterations involving phospholipid and fatty acid metabolism in primary liver cancer. Chronic liver disease appears to be associated with diminishing hepatic phospholipid reserve. Note: This abstract was not presented at the meeting. Citation Format: Sandi Alexander Kwee, Adrian A. Franke, Laurie J. Custer, Xingnan Li, Linda L. Wong. Fatty acid and phospholipid profiling of liver tumor tissue: correlation with in vivo molecular PET imaging of phosphocholine synthesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1486. doi:10.1158/1538-7445.AM2015-1486

Value of functional imaging by PET in esophageal cancer.

In esophageal cancer, functional imaging using PET can provide important additional information beyond standard staging techniques that may eventually lead to therapeutic consequences. The most commonly used tracer is fluorodeoxyglucose (FDG), which has high avidity for both squamous cell cancer and adenocarcinoma of the esophagus. The value of FDG-PET is limited in early esophageal cancer, whereas additional information is provided in 15% to 20% of locally advanced tumors. Neoadjuvant treatment is currently the standard of care in locally advanced esophageal cancer in most countries because randomized studies have shown a significant survival benefit. Because responders and nonresponders have a significantly different prognosis, functional imaging to tailor preoperative treatment would be of interest. Metabolic imaging using FDG-PET is an established method of response evaluation in clinical trials. The value of metabolic response evaluation is known to depend on the histologic subtype and the type of preoperative treatment delivered. An association of FDG-PET-based metabolic response with clinical response and prognosis was shown for absolute standardized uptake value (SUV) or a decrease of SUV levels before, during, and after therapy. However, contradictory findings exist in the literature and prospective validation is missing. Additionally, no consensus exists on time points or cutoff levels for metabolic response evaluation. Furthermore, correct prediction of a posttherapeutic pathologic complete remission is currently not possible using FDG-PET. Of high interest is early response monitoring during preoperative chemotherapy, with potential subsequent therapy modification. This tailored approach still needs validation in prospective multicenter trials.

Utilization of 18F-FDG PET/CT as a staging tool in patients with newly diagnosed lymphoma

The aim of this study was to investigate the role of 2-fluorine-18-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the initial staging and prediction of bone marrow involvement in patients with newly diagnosed lymphoma. A total of 185 patients with newly diagnosed lymphoma were enrolled. All patients received PET/CT and bone marrow biopsy as part of a staging work-up. At the initial staging, 17 patients (9.2%) with occult nodal or extranodal lesions were upstaged after a review of the PET/CT studies. PET/CT was found to be useful in the differentiation of aggressive lymphoma subtypes from the indolent subtype based on higher standardized uptake value (SUV) (16.67 vs. 7.98, p < 0.001). The results of bone marrow biopsy and PET/CT in the detection of bone marrow involvement were concordant in 152 patients (82.1%); positive concordance was observed in 21 patients, and negative concordance was observed in 131 patients. A high concordance rate was found between aggressive B cell lymphoma and Hodgkin's lymphoma (88.1% and 93.8%, respectively). High negative predictive values (NPVs) for excluding bone marrow involvement were observed in aggressive B-cell lymphoma (93.2%) and Hodgkin's lymphoma (100%). Diffuse bone marrow FDG uptake accurately predicted bone marrow in aggressive B-cell lymphoma with a positive predictive value (PPV) of 100%. The concordance rate was lower in indolent B-cell lymphoma (66.0%). In conclusion, PET/CT resulted in the upstaging of patients with occult extranodal or nodal lesions. A high SUV level can predict aggressive subtype of lymphoma and detect aggressive components in indolent lymphoma. PET/CT had a high PPV for aggressive B-cell lymphoma with diffuse bone marrow FDG uptake and high NPVs for excluding bone marrow involvement in aggressive B-cell lymphoma and Hodgkin's lymphoma. Bone marrow biopsy may be omitted for the above subgroups of patients with medical conditions not suitable for this procedure. For patients with indolent B-cell lymphoma, bone marrow biopsy is still an indispensable procedure for staging.

(18)F-FDG PET/CT of advanced gastric carcinoma and association of HER2 expression with standardized uptake value.

Expression of HER2 in gastric carcinoma has direct prognostic and therapeutic implications in patient management. The aim of this study is to determine whether a relationship exists between standardized uptake value (SUV) and expression of HER2 in advanced gastric carcinoma. We analyzed the (18)F-FDG PET/CT results of 109 patients that underwent gastrectomy for advanced gastric carcinoma. The (18)F-FDG PET/CT imaging was requested at the initial staging before surgery. The examinations were evaluated semi-quantitatively, with calculation of maximum standardized uptake values (SUVmax). The clinicopathologic factors, including HER2 overexpression, were determined from tissue obtained from the primary tumor. Metabolic and clincopathologic parameters were correlated using a t-test, one way ANOVA and chi-square test. Immunohistochemically, 26 patients (23.8%) showed HER2 overexpression. This overexpression was significantly associated with high SUV level (P=0.02). The SUV level was significantly correlated with tumor size (P=0.02) and differentiation (P<0.001), and Lauren histologic type (P=0.04). Multivariate analysis showed HER2 overexpression, large tumor size, and differentiation (P=0.022, P=0.002, P<0.001) were significantly correlated with the high level of SUV in advanced gastric carcinoma. No association was found between SUV and T stage and lymph node metastasis. A receiver-operating characteristic curve demonstrated a SUVmax of 3.5 to be the optimal cutoff for predicting HER2 overexpression (sensitivity; 76.9%, specificity; 60.2%). An association exists between high SUV and HER2 overexpression and (18)F-FDG PET/CT could be a useful tool to predict the biological characteristics of gastric carcinoma.

Adrenergic pathway activation enhances brown adipose tissue metabolism: A [18F]FDG PET/CT study in mice

Pharmacologic approaches to study brown adipocyte activation in vivo with a potential of being translational to humans are desired. The aim of this study was to examine pre- and postsynaptic targeting of adrenergic system for enhancing brown adipose tissue (BAT) metabolism quantifiable by [(18)F]fluoro-2-deoxyglucose ([(18)F]FDG) positron emission tomography (PET)/computed tomography (CT) in mice. A β₃-adrenoreceptor selective agonist (CL 316243), an adenylyl cyclase enzyme activator (forskolin) and a potent blocker of presynaptic norepinephrine transporter (atomoxetine), were injected through the tail vein of Swiss Webster mice 30 minutes before intravenous (iv) administration of [(18)F]FDG. The mice were placed on the PET/CT bed for 30 min PET acquisition followed by 10 min CT acquisition for attenuation correction and anatomical delineation of PET images. Activated interscapular (IBAT), cervical, periaortic and intercostal BAT were observed in 3-dimentional analysis of [(18)F]FDG PET images. CL 316243 increased the total [(18)F]FDG standard uptake value (SUV) of IBAT 5-fold greater compared to that in placebo-treated mice. It also increased the [(18)F]FDG SUV of white adipose tissue (2.4-fold), and muscle (2.7-fold), as compared to the control. There was no significant difference in heart, brain, spleen and liver uptakes between groups. Forskolin increased [(18)F]FDG SUV of IBAT 1.9-fold greater than that in placebo-treated mice. It also increased the [(18)F]FDG SUV of white adipose tissue (2.2-fold) and heart (5.4-fold) compared to control. There was no significant difference in muscle, brain, spleen, and liver uptakes between groups. Atomoxetine increased [(18)F]FDG SUV of IBAT 1.7-fold greater than that in placebo-treated mice. There were no significant differences in all other organs compared to placebo-treated mice except liver (1.6 fold increase). A positive correlation between SUV levels of IBAT and CT Hounsfield unit (HU) (R(2)=0.55, p<0.001) and between CT HU levels of IBAT and liver (R(2)=0.69, p<0.006) was observed. The three pharmacologic approaches reported here enhanced BAT metabolism by targeting different sites in adrenergic system as measured by [(18)F]FDG PET/CT.

The Significance of Alteration 2-[fluorine-18]fluoro-2-deoxy-d-glucose Uptake in the Liver and Skeletal Muscles of Patients with Hyperthyroidism

Hyperthyroidism leads to an enhanced demand for glucose. The hypothesis of the study is that 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) can demonstrate the alteration of systemic glucose metabolism in hyperthyroidism patients by measuring the FDG standard uptake value (SUV) in liver and skeletal muscle. Forty-eight active hyperthyroidism patients and 30 control participants were recruited for the study. The intensity of FDG uptake in the liver and thigh muscles was graded subjectively, comprising three groups: group I, higher FDG uptake in the liver; group II, equal FDG uptake in the liver and muscles; and group III, higher FDG uptake in the muscles. Ten subjects with FDG PET scans at hyperthyroid and euthyroid status were analyzed. Serum levels of thyroxine (T4) and triiodothyronine (T3) correlated to the SUVs of the liver and muscles. Forty-one patients (41/48, 85.4%) showed symmetrically increased FDG uptake in the muscles (22 in group I, 9 in group II, and 17 in group III). Group I patients were significantly older than group II (P = .02) and group III (P = .001) patients. The correlation coefficient between the serum T3, T4, and SUV levels in the muscles was significant (r = 0.47-0.77, P < .01), particularly in liver and muscle FDG uptake between hyperthyroid and euthyroid states. In the 30 control subjects, there was normal physiological FDG uptake in the liver and muscles. In PET scans showing a pattern of decreased liver and increased skeletal muscle FDG uptake in hyperthyroidism patients, this change of FDG distribution is correspondence to the severity of hyperthyroidism status.

Prospective correlative study of FDG-PET SUV and proteomic profile (VeriStrat) of non-small cell lung cancer patients treated with erlotinib.

e18096 Background: Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI TOF MS) was used to create and validate a plasma proteomic algorithm VeriStrat (VS), based on 8 m/z peaks, and able to select advanced NSCLC pts who may benefit from EGFR TKIs. The algorithm was associated with PFS and OS of patients treated with EGFR TKIs and not with chemotherapy. Standardized Uptake Value (SUV) is of prognostic value for survival in non-small cell lung cancer. Aim of the current study was to analyze the OS and TTP in advanced NSCLC pts treated with erlotinib (E) according to baseline VeriStrat classification and baseline SUVs of FDG-PET. Methods: Plasma samples were collected before the beginning of E from metastatic NSCLC patients. Acquired spectra were classified according to the VeriStrat algorithm. The FDG-PET was performed the day before the beginning of E. Results: Thirty eight NSCLC pts on E therapy with the following characteristics were analyzed: median age 62 years old, 63% were males, 53% had adenocarcinoma histology, response rate was 26%, median OS 10 mos and (TTP) 3.4 mos. Twenty-six (68%) were classified as VS Good, 12 (32%) as Poor. TTP and OS for VS Good and Poor were 4.1 vs 2.1 mos (HR 0.86, log-rank p=0.6) and 11.1 vs 4.1 mos (HR 0.45,log-rank p=0.02), respectively. Baseline SUV levels were associated with TTP (Wilcoxon test p=0.001) but not with OS (all pts progressed, 5 still alive). All Poor classified pts had SUV ≥ 7 and had the worst TTP and OS; VS Good classified patients had worse TTP and OS if their baseline SUV level was &gt; 7 than those who were VS Good and had SUV&lt;7(see Table: 3-curves comparison log-rank test p value for a trend). Conclusions: We confirmed that pts with VS Poor classification have significantly shorter OS than those classified as VS Good. Pts with VS Good profile and with low baseline SUV levels may benefit more from EGFR TKI than VS Good pts with high SUV.

Use of early 18f-fluorodeoxyglucose-positron emission tomography to predict clinical outcome of patients with advanced non-small cell lung cancer on gefitinib treatment versus carboplatin plus paclitaxel.

10577 Background: Early prediction of clinical efficacy is of great value in cancer patients in avoiding unnecessary toxicities and giving them another chance for different treatments. This study aimed to assess the 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) at 3 days on treatment as an early predictor of clinical outcome in patients with advanced non-small cell lung cancer (NSCLC) treated with gefitinib and in those treated with cytotoxic chemotherapy. Methods: This study comprised two groups: patients with stage IIIB or IV NSCLC were treated with gefitinib (250mg) once daily (gefitinib group) or with carboplatin (AUC 6, day 1) plus paclitaxel (200mg/m2, day 1) q21 days (CP group) according to the physicians’ choice. FDG-PET was performed before, 3 days on and 28 days on each treatment. Reduction of tumor FDG uptake was assessed by using standardized uptake value (SUV). Metabolic response was defined as reduction of FDG uptake in the tumor ≥ 25% according to the criteria of the European Organization for Research and Treatment of Cancer. Metabolic response was correlated with clinical outcomes. Results: This study included 38 patients: 19 in gefitinib group and 19 in CP group. Reduction of SUV at 3days on treatment preceded tumor shrinkage more closely in gefitinib group. Metabolic response was significantly correlated with longer progression-free survival (PFS) in gefitinib cohort (median PFS 15.8 months [95% CI 13.2-18.4] vs. 3.7 months [95% CI 0.1-8.0], p &lt; 0.001), but not in CP group (median PFS 5.7 months vs. 2.9 months, p = 0.054). Furthermore, metabolic response was significantly correlated with longer overall survival (OS) in gefitinib group (median OS 28.7 months [95%CI 23.5-33.9] vs. 9.8 months [95% CI 2.1-17.5], p = 0.009), but not in CP group (median OS 13.9 months vs. 10.5 months, p = 0.56). In multivariate analysis using Cox hazards models, metabolic response was a significant predictive factor of PFS and OS. Conclusions: Reduction of SUV levels on FDG-PET at 3 days on treatment may predict response and survival in gefitinib-treated patients with advanced NSCLC.