Young Seok Cho

Prognostic Value of Metabolic Tumor Volume Measured by 18F-Fluorodeoxyglucose Positron Emission Tomography in Patients with Esophageal Carcinoma

PurposeThe aim of this study was to evaluate the prognostic value of metabolic tumor volume (MTV) measured by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with esophageal carcinoma.MethodsWe retrospectively reviewed 151 patients with pathologically proven esophageal carcinoma (146 squamous cell carcinomas and 5 adenocarcinomas) who underwent pretreatment 18F-FDG PET. MTV and maximum standardized uptake value (SUVmax) for the primary tumors were measured by 18F-FDG PET. The prognostic significance of MTV, SUVmax, and other clinicopathological variables was assessed by Cox proportional hazards regression analysis. To further evaluate and compare the predictive performance of PET parameters, MTV and SUVmax, time-dependent receiver operating characteristic curve (ROC) analysis was used.ResultsIn the univariate analysis, age, American Joint Committee on Cancer (AJCC) stage, tumor–node–metastasis (TNM) factors, MTV, and SUVmax of primary tumor were significant predictors of survival. On multivariate analysis adjusted for age, sex, and treatment modality, independent predictive factors associated with decreased overall survival were T stage [hazard ratio (HR) 4.325, Pxa0=xa00.006], M stage (HR 2.009, Pxa0=xa00.007), and MTV (HR 1.013, Pxa0=xa00.021). SUVmax was not a significant factor (HR 0.97, Pxa0=xa00.061). On time-dependent ROC analysis, MTV showed good predictive performance for overall survival consistently better than SUVmax.ConclusionMTV, a volumetric parameter of 18F-FDG PET, is an important independent prognostic factor for survival and a better predictor of survival than SUVmax for the primary tumor in patients with esophageal carcinoma.

Prognostic Value of Volume-Based Metabolic Parameters Measured by 18 F-FDG PET/CT of Pancreatic Neuroendocrine Tumors

PurposeTo date, the prognostic value of 18F-FDG PET/CT for patients with pancreatic neuroendocrine tumors (PNETs) has not been well characterized. We investigated the prognostic value of volumetric parameters using 18F-FDG PET/CT in this patient population.MethodsWe retrospectively reviewed 20 cases of pathologically proven PNET in patients who had undergone pre-therapeutic 18F-FDG PET/CT. PET parameters including maximum and average standardized uptake values (SUVmax, SUVave), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were measured using a threshold SUV to determine the boundaries of the tumors. Univariate and multivariate survival analyses were performed with adjustments for PET parameters and other clinical values.ResultsThe median clinical follow-up was 22.3 (range, 1.2–95.4)xa0months. Cancer-related death occurred in 5 of 20 patients (25xa0%). Patients had clinical or pathological stages of I in seven patients, II in six patients, III in three patient, and IV in four patients. According to the WHO histological classification of subtypes, 3 patients exhibited well-differentiated PNETs, 13 patients had well-differentiated endocrine carcinomas, and 4 had poorly differentiatedendocrine carcinomas. Univariate analysis showed that tumor size (pu2009=u20090.028), AJCC stage (pu2009=u20090.009), T stage (pu2009=u20090.028), M stage (pu2009=u20090.029), treatment modality (pu2009=u20090.045), MTV (pu2009=u20090.003) and TLG (pu2009=u20090.027) were significant predictors of overall survival. On multivariate analysis, MTV (HRu2009=u200910.859, pu2009=u20090.031) was a significant independent predictor of overall survival along with the AJCC stage (HRu2009=u200911.556, pu2009=u20090.027).ConclusionIn patients with PNETs, the MTV of the primary tumor as measured by 18F-FDG PET/CT along with the AJCC stage may be a significant independent prognostic factor for overall survival.

Hepatic FDG uptake is associated with future cardiovascular events in asymptomatic individuals with non-alcoholic fatty liver disease.

BackgroundHepatic F-18 fluoro-2-deoxyglucose (FDG) uptake is associated with non-alcoholic fatty liver disease (NAFLD) which is an independent risk factor for cardiovascular disease. However, the value of hepatic FDG uptake for predicting future cardiovascular events has not been explored.Methods and ResultsStudy participants were 815 consecutive asymptomatic participants who underwent a health screening program that included FDG positron emission tomography/computed tomography (PET/CT), abdominal ultrasonography, and carotid intima-media thickness (CIMT) measurements (age 51.8xa0±xa06.0xa0year; males 93.9%). We measured hepatic FDG uptake and assessed the prognostic significance of this parameter with other cardiovascular risk factors including Framingham risk score and CIMT. Multivariate Cox proportional hazards analyses including all study participants revealed that NAFLD with high-hepatic FDG uptake was the only independent predictor for future cardiovascular events [hazard ratio (HR) 4.23; 95% CI 1.05-17.04; Pxa0=xa0.043). Subgroup analysis conducted in the NAFLD group showed that high-hepatic FDG uptake was a significant independent predictor of cardiovascular events (HR 9.29; 95% CI 1.05-81.04; Pxa0=xa0.045).ConclusionsThis exploratory study suggests that high-hepatic FDG uptake may be a useful prognostic factor for cardiovascular events in individuals with NAFLD.

Hepatic Glucose Uptake Is Increased in Association with Elevated Serum γ-Glutamyl Transpeptidase and Triglyceride

BackgroundSubjects with fatty liver disease (FLD) can show increased hepatic 2-deoxy-2-(18F)fluoro-d-glucose (FDG) uptake, but the role of hepatic inflammation has not been explored.AimsWe investigated whether hepatic inflammatory response, as implicated by elevated serum markers, is associated with increased liver FDG uptake in FLD.MethodsLiver sonography and FDG positron emission tomography was performed in 331 asymptomatic men with nonalcoholic FLD (NAFLD), 122 with alcoholic FLD (AFLD), and 349 controls. Mean standard uptake value (SUV) of liver FDG uptake was compared to cardiac risk factors and serum markers of liver injury.ResultsHepatic FDG mean SUV was increased in NAFLD (2.40xa0±xa00.25) and AFLD groups (2.44xa0±xa00.25) compared to controls (2.28xa0±xa00.26; both Pxa0<xa00.001). Both FLD groups also had higher serum γ-glutamylranspeptidase (GGT), triglyceride (TG), hepatic transaminases, and LDL. High GGT and TG levels were independent determinants of increased FDG uptake for both FLD groups. Hepatic mean SUV significantly increased with high compared to low GGT for NAFLD (2.48xa0±xa00.28 vs. 2.37xa0±xa00.24), AFLD (2.51xa0±xa00.27 vs. 2.39xa0±xa00.23), and control groups (2.39xa0±xa00.22 vs. 2.26xa0±xa00.26). High TG increased hepatic mean SUV in AFLD and control groups. Furthermore, serum GGT and TG levels significantly correlated to hepatic mean SUV in all three groups.ConclusionsHepatic FDG uptake is closely associated with elevated TG and GGT regardless of the presence of FLD. Thus, inflammation response may play a major role in increased hepatic glucose uptake.

Comparison of Uptake Characteristics and Prognostic Value of 201Tl and 18F-FDG in Esophageal Cancer

BackgroundPatients with esophageal cancer often undergo 201Tl myocardial imaging for preoperative risk evaluation, thereby providing an excellent opportunity to assess tumor handling of 201Tl. We thus compared the characteristics of 201Tl and 18F-FDG uptake by esophageal cancer and further investigated their prognostic values.MethodsThe study included 100 newly diagnosed esophageal cancer patients who underwent preoperative 201Tl SPECT and 18F-FDG PET exams. Tumor to mediastinal uptake (T/M) ratio and retention index (RI) of 201Tl, tumor 18F-FDG pSUV, tumor size, location, and stage were assessed. Survival analysis was performed for disease-free survival using the Kaplan–Meier method. Cox proportional hazard models were used to determine independent risk factors.Results201Tl SPECT and 18F-FDG PET visualized the primary tumor in 85/100 (85.0%) and 91/100 (91.0%) patients, respectively (pxa0=xa00.03). There were close correlations between early and delayed 201Tl T/M ratios (rxa0=xa00.83, pxa0<xa00.0001) and between T/M ratios and 18F-FDG pSUV (rxa0=xa00.56 and 0.57, respectively, both pxa0<xa00.0001). Both T/M ratios and 18F-FDG pSUV correlated significantly with tumor stage (ρxa0=xa00.45, 0.40, and 0.59, respectively, all pxa0<xa00.0001). Survival analysis revealed tumor size, 201Tl negative tumors, 18F-FDG negative tumors, delayed 201Tl T/M ratio, RI, stage, and 18F-FDG pSUV to be significant univariate predictors for disease-free survival. Multivariate survival analysis showed stage (pxa0=xa00.02) to be a significant independent prognostic predictor.ConclusionsIn patients with esophageal cancer, assessment of tumor 201Tl uptake, as with 18F-FDG, may provide potentially useful information regarding tumor characteristics.

Imaging Early Fate of Cancer Stem Cells in Mouse Hindlimbs with Sodium Iodide Symporter Gene and I-124 PET

PurposeWe investigated the capacity of sodium/iodide symporter (NIS) positron emission tomography (PET) to image and quantitate early engraftment and survival of cancer stem cells (CSCs) in living mice.ProceduresCT26 colon cancer cells and CSCs were infected with an adenovirus expressing both NIS and enhanced green fluorescent protein (EGFP). Cells were implanted into normal and ischemic hindlimbs of mice, and serial optical and I-124 PET imaging was performed. Extracted tissues underwent I-124 measurements and confocal microscopy.ResultsNIS.EGFP gene transfer increased fluorescence and I-124 uptake of CSCs and CT26 cells without adverse effects. I-124 PET clearly visualized implanted tumor cells in vivo, whereas optical imaging was suboptimal. PET revealed 1.95, 2.22, and 1.93-fold greater I-124 uptake by CSC inoculation into ischemic compared to non-ischemic limbs at 2, 15, and 24xa0h, respectively. CT26 cells showed similar but smaller differences. PET findings were confirmed by ex vivo measurements and confocal microscopy.ConclusionsNIS PET can help identify microenvironment conditions that influence early survival of implanted CSCs.

18F-AV-1451 PET Imaging in Three Patients with Probable Cerebral Amyloid Angiopathy

Cerebrovascular deposition of amyloid-β, known as cerebral amyloid angiopathy (CAA), is associated with MRI findings of lobar hemorrhage, cerebral microbleeds, and cortical superficial siderosis. Although pathological studies suggest that tau may co-localize with vascular amyloid, this has not yet been investigated in CAA in vivo. Three patients with probable CAA underwent 11C-Pittsburgh Compound B (PiB) PET or 18F-florbetaben PET to evaluate amyloid burden, and 18F-AV-1451 PET to evaluate paired helical filament tau burden. Regions that had cerebral microbleeds or cortical superficial siderosis largely overlapped with those showing increased 18F-AV-1451. Our preliminary study raised the possibility that lobar cerebral microbleeds, and cortical superficial siderosis, which are characteristic markers of vascular amyloid, may be associated with local production of paired helical filament tau.

Intra-patient Variability of FDG Standardized Uptake Values in Mediastinal Blood Pool, Liver, and Myocardium during R-CHOP Chemotherapy in Patients with Diffuse Large B-cell Lymphoma.

Purpose18F-fluorodeoxyglucose (FDG) PET/CT is useful for staging and evaluating treatment response in patients with diffuse large B-cell lymphoma (DLBCL). A five-point scale model using the mediastinal blood pool (MBP) and liver as references is a recommended method for interpreting treatment response. We evaluated the variability in standardized uptake values (SUVs) of the MBP, liver, and myocardium during chemotherapy in patients with DLBCL.MethodsWe analyzed 60 patients with DLBCL who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) treatment and underwent baseline, interim, and final FDG PET/CT scans. The FDG uptakes of lymphoma lesions, MBP, liver, and myocardium were assessed, and changes in the MBP and liver SUV and possible associated factors were evaluated.ResultsThe SUV of the liver did not change significantly during the chemotherapy. However, the SUVmean of MBP showed a significant change though the difference was small (pu2009=u20090.019). SUVmean of MBP and liver at baseline and interim scans was significantly lower in patients with advanced Ann Arbor stage on diagnosis. The SUVmean of the MBP and liver was negatively correlated with the volumetric index of lymphoma lesions in baseline scans (ru2009=u2009-0.547, pu2009<u20090.001; ru2009=u2009-0.502, pu2009<u20090.001). Positive myocardial FDG uptake was more frequently observed in interim and final scans than in the baseline scan, but there was no significant association between the MBP and liver uptake and myocardial uptake.ConclusionsThe SUV of the liver was not significantly changed during R-CHOP chemotherapy in patients with DLBCL, whereas the MBP SUV of the interim scan decreased slightly. However, the SUV of the reference organs may be affected by tumor burden, and this should be considered when assessing follow-up scans. Although myocardial FDG uptake was more frequently observed after R-CHOP chemotherapy, it did not affect the SUV of the MBP and liver.

Clinical Significance of Incidental Focal 18F-FDG Uptake in the Spinal Cord of Patients with Cancer

PurposeWe investigated the incidence, location, and clinical significance of focal 18F-FDG uptake of the spinal cord in patients with cancer.MethodsWe reviewed the medical records of 22,937 consecutive adult patients with known or suspicious malignancy who underwent 18F-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 (SUVmax) 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.ResultsIncidental focal spinal cord uptake was observed in 69 of 22,937 adult patients (incidenceu2009=u20090.3%; M:Fu2009=u200931:38; age, 55.8u2009±u200914.7xa0years). 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 SUVmax for cord uptake was 2.5u2009±u20090.5 (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.ConclusionsAlthough incidental focal 18F-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.

Strong association of epidermal growth factor receptor status with breast cancer FDG uptake

PurposeImaging 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.MethodsThis 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 ≥xa08.6).ResultsSUVmax was higher in ER- (36.5%; 11.2xa0±xa06.0 vs. 8.3xa0±xa05.3), PR- (42.3%; 10.9xa0±xa06.0 vs. 8.2xa0±xa05.2), and triple-negative tumors (19.8%; 12.0xa0±xa06.9 vs. 8.7xa0±xa05.2; all pxa0<xa00.0001). EGFR expression (28.5%) was more frequent in ER-, PR-, triple-negative, cytokeratin 5/6 (CK5/6)xa0+xa0and mutant P53 (mP53)xa0+xa0tumors (all pxa0<xa00.0001). EGFR+ was associated with higher SUVmax among all tumors (11.9xa0±xa06.0 vs. 8.3xa0±xa05.3), ER- tumors (pxa0<xa00.0001), PR- and + tumors (pxa0<xa00.0001 and 0.027), hormone receptor- and + tumors (pxa0<xa00.0001 and 0.004), human epidermal growth factor receptor 2 (HER2)- and + tumors (pxa0<xa00.0001 and 0.006), non-triple negative tumors (pxa0<xa00.0001), CK5/6- and + tumors (pxa0=xa00.021 and <0.0001), and mP53- and + tumors (pxa0<xa00.0001 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 mP53xa0+.ConclusionsPrimary 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.