Mijin Yun

Usefulness of 18F-FDG PET in intrahepatic cholangiocarcinoma.

Surgical resection is the only curative treatment strategy for intrahepatic cholangiocarcinoma (CC). Therefore, accurate staging is essential for appropriate management of patients with CC. We assessed the usefulness of 2-[18F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in the staging of CC. We undertook a retrospective review of FDG PET images in 21 patients (10 female, 11 male; mean age 57 years) diagnosed with CC. Ten patients had hilar CC and 11, peripheral CC. Patients underwent abdominal magnetic resonance imaging (MRI) (n=20) and computed tomography (CT) (n=12) for the evaluation of primary tumours, and chest radiography and whole-body bone scintigraphy for work-up of distant metastases. For semi-quantitative analysis, the maximum voxel standardised uptake value (SUVmax) was obtained from the primary tumour. All peripheral CCs showed intensely increased FDG uptake, and some demonstrated ring-shaped uptake corresponding to peripheral rim enhancement on CT and/or MRI. In nine of the ten patients, hilar CCs demonstrated increased FDG uptake of a focal nodular or linear branching appearance. The remaining case was false negative on FDG PET. One patient with a false negative result on MRI demonstrated increased uptake on FDG PET. Among the ten hilar CCs, FDG uptake was intense in only two patients and was slightly higher than that of the hepatic parenchyma in the remaining patients. For the detection of lymph node metastasis, FDG PET and CT/MRI were concordant in 16 patients, and discordant in five (FDG PET was positive in three, and CT and MRI in two). FDG PET identified unsuspected distant metastases in four of the 21 patients; all of these patients had peripheral CC. FDG PET is useful in detecting the primary lesion in both hilar and peripheral CC and is of value in discovering unsuspected distant metastases in patients with peripheral CC. FDG PET could be useful in cases of suspected hilar CC with non-confirmatory biopsy and radiological findings.

Role of 18F-Fluorodeoxyglucose Positron Emission Tomography in Detecting Extrahepatic Metastasis in Pretreatment Staging of Hepatocellular Carcinoma

Objectives:18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is useful for differentiating benign from malignant lesions, evaluating tumor stage, monitoring the response to therapy and detecting tumor recurrence in a variety of malignancies. Nevertheless, its use in patients with hepatocellular carcinoma (HCC) is still uncertain. We evaluated whether FDG-PET has a role in detecting extrahepatic metastasis in pretreatment tumor staging of HCC and the characteristics of patients with extrahepatic metastasis that benefit from FDG-PET. Methods: Eighty-seven patients with HCC underwent computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and chest X-ray to evaluate pretreatment tumor staging. FDG-PET was then performed to detect extrahepatic metastasis. The power of FDG-PET to detect extrahepatic metastasis was compared with that of conventional images. In addition, we evaluated whether the detection of extrahepatic metastasis using FDG-PET changed the TNM stage. Moreover, we investigated the clinical and tumor characteristics of patients with extrahepatic HCC metastasis. Results: Extrahepatic metastases were identified in 24 of 87 patients. The location and frequency of metastases were lung 12, lymph nodes 19 and bone 11. All of the extrahepatic metastases were detected by FDG-PET. In addition, FDG-PET identified 4 lymph node metastases and 6 bone metastases that were not found using conventional methods. The initial TNM stage based on the conventional staging workup was changed in 4 cases after FDG-PET. Extrahepatic metastasis was significantly more frequent in patients with intrahepatic tumor >5 cm in size (p = 0.045). Conclusions: FDG-PET is a useful imaging modality for identifying extrahepatic metastases which may lead to accurate staging and proper management of patients with possible extrahepatic metastases.

UCP2-induced fatty acid synthase promotes NLRP3 inflammasome activation during sepsis

Cellular lipid metabolism has been linked to immune responses; however, the precise mechanisms by which de novo fatty acid synthesis can regulate inflammatory responses remain unclear. The NLRP3 inflammasome serves as a platform for caspase-1-dependent maturation and secretion of proinflammatory cytokines. Here, we demonstrated that the mitochondrial uncoupling protein-2 (UCP2) regulates NLRP3-mediated caspase-1 activation through the stimulation of lipid synthesis in macrophages. UCP2-deficient mice displayed improved survival in a mouse model of polymicrobial sepsis. Moreover, UCP2 expression was increased in human sepsis. Consistently, UCP2-deficient mice displayed impaired lipid synthesis and decreased production of IL-1β and IL-18 in response to LPS challenge. In macrophages, UCP2 deficiency suppressed NLRP3-mediated caspase-1 activation and NLRP3 expression associated with inhibition of lipid synthesis. In UCP2-deficient macrophages, inhibition of lipid synthesis resulted from the downregulation of fatty acid synthase (FASN), a key regulator of fatty acid synthesis. FASN inhibition by shRNA and treatment with the chemical inhibitors C75 and cerulenin suppressed NLRP3-mediated caspase-1 activation and inhibited NLRP3 and pro-IL-1β gene expression in macrophages. In conclusion, our results suggest that UCP2 regulates the NLRP3 inflammasome by inducing the lipid synthesis pathway in macrophages. These results identify UCP2 as a potential therapeutic target in inflammatory diseases such as sepsis.

Analysis of gene expression profiles of hepatocellular carcinomas with regard to 18F-fluorodeoxyglucose uptake pattern on positron emission tomography

Purpose18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumour aggressiveness and prognosis in various types of cancer. In this study, the gene expression profiles of hepatocellular carcinomas (HCCs) were evaluated to determine whether HCCs with high 18F-FDG uptake have more aggressive biological potential than those with low uptake.MethodsSurgical specimens were obtained from ten patients with HCC (six males and four females, age range 38–68 years). The tumour samples were divided into two groups based on the 18F-FDG PET scan findings: high 18F-FDG uptake (n=4) and low 18F-FDG uptake (n=6).ResultsThe pathological tumour grade was closely correlated with the 18F-FDG uptake pattern: HCCs with high 18F-FDG uptake were pathologically Edmondson-Steiner grade III, while those with low uptake were either grade II or grade II with a focal area of grade III. The total RNA was extracted from the frozen tissues of all HCCs (n=10) and adjacent non-cancerous tissue (n=7). The gene expression profiles were evaluated using an oligoDNA microarray. The HCCs with high 18F-FDG uptake showed increased expression of 11 genes—including vascular cell adhesion molecule-1, vinexin beta and core 1 UDP-galactose:N-acetylgalactosamine-alpha-R-beta 1,3-galactosyltransferase and the natural killer cell inhibitory receptor—compared to those with low uptake (p<0.005). Nine genes, including regulator of mitotic spindle assembly 1, grb2-related adaptor protein and beta-1,3-n-acetylglucosaminyltransferase, were repressed.ConclusionGene expression is closely related to cell survival, cell-to-cell adhesion or cell spreading; therefore, HCCs with high 18F-FDG uptake appear to have more aggressive biological properties than those with low uptake.

High tumor metabolic activity as measured by fluorodeoxyglucose positron emission tomography is associated with poor prognosis in limited and extensive stage small-cell lung cancer

Purpose: We investigated the prognostic effect of incorporating metabolic assessment by 18F-fluoro-2-deoxyglucose uptake on positron emission tomography/computed tomography (18F-FDG-PET/CT) into a conventional staging system in small-cell lung cancer (SCLC). Experimental Design: Seventy-six consecutive patients with pathologically proven SCLC were enrolled. All patients underwent standard treatment after pretreatment 18F-FDG-PET/CT scanning. The mean values of maximal standardized uptake values (meanSUVmax) of the malignant lesions upon 18F-FDG-PET/CT were calculated. The Cox proportional hazards model was used with performance status, lactate dehydrogenase, stage, and meanSUVmax. Results: Patients with high meanSUVmax were significantly related with the established poor prognostic factors, such as higher lactate dehydrogenase (P = 0.04) and extensive disease (ED; P = 0.01). Furthermore, in multivariate analysis, patients with high meanSUVmax were associated with poor survival outcomes compared with patients with low meanSUVmax [adjusted hazard ratio, 3.74; 95% confidence interval (95% CI), 1.67-8.37; P = 0.001, for death and adjusted hazard ratio, 2.25; 95% CI, 1.21-4.17; P = 0.01 for recurrence/progression]. In subgroup analysis, limited disease (LD) with high meanSUVmax showed significantly shorter overall survival than LD with low meanSUVmax [high versus low meanSUVmax, 20.1 months (95% CI, 7.9-23.2) versus 35.3 months (95% CI, 27.6-42.9); P = 0.02]. ED with high meanSUVmax had significantly shorter overall survival than ED with low meanSUVmax [high versus low meanSUVmax, 9.5 months (95% CI, 4.9-13.9) versus 17.7 months (95% CI, 12.0-20.1); P = 0.007]. These findings were replicated in progression-free survival analysis. Conclusions: In SCLC, tumor metabolic activity as assessed by FDG-PET is a significant prognostic factor and identifies subgroups of patients at higher risk of death in both LD and ED SCLC.

The utility of F-18 FDG PET/CT in the evaluation of pancreatic intraductal papillary mucinous neoplasm.

Purpose: To assess the utility of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in evaluating pancreatic intraductal papillary mucinous neoplasm (IPMN). Materials and Methods: We included 31 patients with pancreatic IPMN who underwent F-18 FDG PET/CT and multidetector CT (MDCT). Each pancreatic lesion was classified as benign or malignant. On PET, the maximal standardized uptake value was measured in each pancreatic lesion. Results: PET/CT was superior to MDCT in diagnosing malignant IPMN. All 22 concordant results gave accurate diagnoses. Of 9 discordant results, MDCT misdiagnosed 7 IPMNs, whereas PET/CT misinterpreted 2. Malignant IPMNs showed significantly higher maximal standardized uptake values (mean ± standard deviation, 6.7 ± 3.6) than benign IPMNs (mean ± standard deviation, 2.1 ± 1.0) (P < 0.001). Conclusions: F-18 FDG PET/CT outperformed MDCT in detecting malignant IPMN.

Drug-loaded gold plasmonic nanoparticles for treatment of multidrug resistance in cancer.

To investigate the possibility of treating multidrug-resistant tumors with targeted chemo-photothermal treatment, we conducted in vitro and in vivo studies using a doxorubicin (DOX)-resistant DLD-1 cell line (DLD-1/DOX) and nude mice with human xenograft tumors, respectively. The chemo-photothermal treatment consisted of DOX-loaded-poly(lactic-co-glycolic acid)-Au half-shell nanoparticles with targeting moieties of anti-death receptor-4 monoclonal antibody conjugated to the Au surface. The cells or xenografted tumors treated with nanoparticles were exposed to near infrared light for 10 min, which caused an increase in temperature to 45 °C. Chemo-photothermal treatment resulted in a large reduction in the rate of tumor xenograft growth on DLD-1/DOX tumor-bearing mice with a much smaller dose of DOX than conventional DOX chemotherapy. These results demonstrate that targeted chemo-photothermal treatment can provide high therapeutic efficacy and low toxicity in the treatment of multidrug-resistant tumors.

Thyroid Incidentalomas Identified by 18F-FDG PET: Sonographic Correlation

OBJECTIVE The purpose of this study was to evaluate the risk of malignancy of thyroid incidentalomas detected on (18)F-FDG PET and the diagnostic accuracy of sonography for differentiating benign from malignant focal thyroid incidentalomas that were detected on FDG PET. MATERIALS AND METHODS Retrospective review was performed of a database of 87 focal thyroid lesions seen on FDG PET and sonography. Forty-two focal lesions were malignant. We compared the accuracy of the maximum standard uptake value (SUV) to differentiate benign from malignant thyroid lesions. We classified the thyroid nodules as probably benign or suspicious for malignancy by the sonographic features. Statistical analyses compared two subgroups by sonographic classifications between benign and malignant thyroid lesions. RESULTS The maximum SUV of the malignant nodules was not significantly higher than that of benign lesions. Thirty-seven (75.5%) of 49 lesions with suspicious sonographic findings revealed malignancy on cytopathology, compared with five (13.2%) of 38 lesions that showed probably benign sonographic findings. These differences were statistically significant using a kappa test (kappa = 0.675, p = 0.001) and logistic regression (odds ratio = 26.2, p = 0.001). CONCLUSION The probability (48.3%) of malignancy of focal thyroid incidentalomas seen on FDG PET is high. The maximum SUV of thyroid cancer is not significantly higher than that of benign lesions. The probability (13.2%) of malignancy is much lower when the sonographic findings appear benign, as compared with a significantly higher probability (75.5%) of malignancy when the sonographic findings are suspicious for malignancy.

Cortical surface-based analysis of 18F-FDG PET: Measured metabolic abnormalities in schizophrenia are affected by cortical structural abnormalities

The purpose of the study is to propose a new framework for surface-based statistical parametric mapping of PET images using MRI-based cortical surface analysis, including partial volume correction, intensity normalization and spatial normalization on the cortical surface. Maximum PET intensities along the path between inner and outer layer of the cortical gray matter are mapped onto the cortical surface to generate a metabolic activity surface map. For the partial volume correction, the metabolic activity surface map was divided by the partial volume effect map. The regional metabolic activity was normalized by the global activity iteratively calculated at the surface nodes, statistically independent of the group, as measured by F statistics. After surface-based spatial normalization, a statistical evaluation of both cortical thickness and cortical metabolic activity was conducted on the normalized surfaces of 16 patients with schizophrenia and 16 age- and gender-matched healthy controls. The patients with schizophrenia were found to have significant cortical thinning in the temporal and inferior frontal cortices. Accordingly, their PET imaging was significantly affected by the partial volume effect, indicating that partial volume correction could change the statistical results. After correction of the partial volume effects, the patients showed hyperactivity in the temporal cortex, whereas hypoactivity in the prefrontal cortex, predominantly in the left hemisphere. Our results demonstrate that anatomical factors affect an analysis for functional data from the PET, and therefore the importance of combining anatomy and function in the analysis of imaging data for schizophrenia should be considered.

Analysis of adrenal masses by 18F-FDG positron emission tomography scanning

This study aimed to analyse the characteristics of adrenal masses visible in the computerised tomography (CT) scans which have been also evaluated by 2‐[18F]fluoro‐2‐deoxy‐D‐glucose positron emission tomography (18F‐FDG PET), and to characterise the features of 18F‐FDG PET scans associated with various adrenal endocrine tumours, especially benign functional tumours. 18F‐FDG PET scans of 105 patients with adrenal masses on the CT scan were analysed. Positive uptakes in the 18F‐FDG PET scans were seen in 60 malignant tumours (54 metastasic lesions, six primary adrenal cancers) and seven benign tumours. The positive predictive value of 18F‐FDG PET imaging to characterise an adrenal mass as a malignant tumour was 90%; the corresponding negative predictive value to rule out malignancy was also 90%. Benign adrenal tumours were smaller than that of malignant lesions (p < 0.05). The mean standardised uptake value max (SUVmax) of the metastatic lesions [8.4 ± 6.5 (μCi/g)/μCi/kg] was significantly higher than that of the benign adrenal tumours [2.4 ± 1.2 (μCi/g)/μCi/kg, p < 0.001]. Examination of only the primary adrenal lesions revealed that all adrenocortical carcinomas, two of three cases of pheochromocytomas, three of five neuroblastomas and two of four cases of primary aldosteronism showed positive 18F‐FDG uptake. In conclusion, for patients presenting adrenal masses with a high probability of malignancy, 18F‐FDG PET can be used to differentiate malignant from benign adrenal lesions. However, the 18F‐FDG PET uptake did not show an always consistent pattern for endocrine tumours, which was probably due to the variability inherent in 18F‐FDG uptake. This study suggests that 18F‐FDG PET scanning can offer supporting data to localise and characterise adrenal tumours.