Molecular biological correlation of fluorine-18 fluorodeoxyglucose uptake in esophageal squamous cell carcinoma.

OBJECTIVE: The aim of this study was to assess the relationship between fluorine-18 fluorodeoxyglucose (F-FDG) uptake and molecular biological markers in esophageal squamous cell carcinoma (ESCC) patients. METHODS: Our patient population included 51 patients who underwent F-FDG PET/computed tomography before surgery. Excised tumor tissue was analyzed immunohistochemically using monoclonal antibodies for glucose transporter-1 (GLUT-1), GLUT-3, CD34 [microvessel density (MVD) marker], CD68 (macrophage marker), and CD163 (tumor-associated macrophage marker). The relationships among pathological factors [pathological T stage (p-T stage), pathological lymph node status (p-N status), pathological stage (p-stage), and pathological tumor length], the maximum standardized uptake value (SUVmax), and these molecular biological markers were evaluated using Spearman's rank test and the Kruskal-Wallis test. RESULTS: GLUT-1, GLUT-3, CD34, and CD163 significantly correlated with SUVmax (r=0.547, P<0.001 for GLUT-1; r=0.569, P<0.001 for GLUT-3; r=0.463, P=0.001 for CD34, r=0.455, P=0.001 for CD163), whereas SUVmax, GLUT-1, GLUT-3, CD34, and CD163 significantly correlated with p-T stage (r=0.552, P<0.001 for SUVmax, r=0.307, P=0.03 for GLUT-1, r=0.349, P=0.013 for GLUT-3, r=0.313, P=0.027 for CD34, r=0.526 for CD163, P<0.001), but not with p-N status. CD68 levels showed no significant correlation with SUVmax, p-T stage, p-stage, or p-N status. CONCLUSION: SUVmax, GLUT-1 expression, GLUT-3 expression, MVD, and TAMs show a relationship with the tumor stage and extent of ESCC. GLUT-1, GLUT-3, MVD, and TAMs are associated with the mechanism of F-FDG uptake in ESCC.

Assessment of 99mTc-MIBI SPECT(/CT) to monitor multidrug resistance-related proteins and apoptosis-related proteins in patients with ovarian cancer: a preliminary study.

OBJECTIVE: Multidrug resistance (MDR) has been suggested to be a major cause of failure of chemotherapy treatment for cancer. It is associated with the expression of MDR-related and apoptosis-related proteins. Recently, technetium-99m hexakis 2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been suggested as a tumor-seeking agent for the detection of MDR. The aim of this study was to evaluate (99m)Tc-MIBI single-photon emission computed tomography (SPECT)(/CT) for functional imaging of MDR-related and apoptosis-related proteins in patients with ovarian cancer. METHODS: Eleven women (mean age 63 years, range 53-76) with a clinical suspicion of ovarian cancer were prospectively studied. All patients were examined with (99m)Tc-MIBI imaging before surgery. After intravenous injection of 740 MBq (99m)Tc-MIBI, SPECT(/CT) imaging at 10 min and 2 h was performed. Based on the semiquantitative analysis of (99m)Tc-MIBI SPECT(/CT), both early and delayed tumor uptake ratios and washout rate % were calculated. The expression of MDR-related and apoptosis-related proteins was assessed in surgically excised tumors. Immunohistochemical staining was performed to quantify the expression levels of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein1 (MRP1), MRP3, lung resistance protein (LRP), breast cancer resistance protein (BCRP), Y-box-binding protein-1 (YB-1), Bcl-2, Bax and glutathione-S-transferase. (99m)Tc-MIBI imaging results and immunohistochemical results were compared. RESULTS: Laparotomy was performed in all patients. Six ovarian cancers were proven by histopathological examination. Five of the six ovarian cancers were positive for (99m)Tc-MIBI uptake on both early and delayed images with (99m)Tc-MIBI SPECT(/CT). MDR-related and apoptosis-related proteins were found to be expressed in all tumors. For the five positive (99m)Tc-MIBI uptake cases, the washout rate % of (99m)Tc-MIBI uptake showed a significant positive correlation with the expression of YB-1 (r = 0.988, P = 0.0015), and the early tumor uptake ratio showed a significant positive correlation with the expression of Bax (r = 0.882, P = 0.047). CONCLUSIONS: Our results suggested that (99m)Tc-MIBI SPECT(/CT) might be a valuable diagnostic imaging technique to evaluate MDR-associated YB-1 and Bax-mediated apoptosis in patients with ovarian cancer.

Hypermetabolic pulmonary and bone marrow lesions in a patient with chronic adult T-cell leukemia.

A 69 years old woman with adult T-cell leukemia (ATL) (chronic type) was referred for a fluorine-18 fluorodeoxyglucose positron emission computed tomography ((18)F-FDG PET/CT). Multiple hypermetabolic pulmonary and bone lesions were evidence. The patient underwent chemotherapy, but did not respond, and she died approximately 8 months from the onset of symptoms. Autopsy showed ATL cells infiltrating the lung parenchyma and the pulmonary hilum. In conclusion, we present a case of hypermetabolic pulmonary lesions associated with thoracic CT findings on a (18)F-FDG PET/CT scan in a patient with a chronic adult T-cell leukemia.

Relationship between 2-deoxy-2-[(18)F]-fluoro-d-glucose uptake and clinicopathological factors in patients with diffuse large B-cell lymphoma.

The aim of this study was to investigate correlations between the standardized uptake value of the biopsy site (BSUVmax) and levels of glucose transporter (GLUT)-1, GLUT-3 and hexokinase-II (HK-II), between BSUVmax and the Ki-67 proliferation index (MIB-1), and between BSUVmax and clinicopathological factors. Sixty-eight patients with diffuse large B-cell lymphoma (DLBCL) were included in this study. BSUVmax was significantly correlated with GLUT-1, GLUT-3 and the International Prognostic Index (IPI) (GLUT-1: r = 0.584, IPI: r = 0.363, p < 0.001; GLUT-3: r = 0.369, p = 0.009; IPI: r = 0.363, p = 0.004), but not with MIB-1 and HK-II. A statistically significant correlation was observed between GLUT-3 expression and each of IPI and gene expression profiling (GEP) (IPI: p = 0.0186; GEP: p = 0.0179). 2-Deoxy-2-[(18)F]-fluoro-d-glucose (FDG) uptake was significantly correlated with the levels of GLUT-1 and GLUT-3 and with IPI. The results indicated that GLUT-3 expression is related to GEP and IPI, and that BSUVmax and GLUT-3 may have a relationship with the prognosis of DLBCL.

The difference in relationship between 18F-FDG uptake and clinicopathological factors on thyroid, esophageal, and lung cancers.

OBJECTIVES: The aim of this study was to reveal the differences in clinicopathological factors affecting maximum standardized uptake value (SUVmax) between esophageal squamous cell carcinoma (ESCC), non-small-cell lung cancer (NSCLC), and papillary thyroid cancer (PTC). METHODS: This study consisted of 119 patients with ESCC (n=43), PTC (n=40), or NSCLC (n=36). We investigated the correlations between SUVmax and clinicopathological factors by using Spearman's correlation coefficient and the Kruskal-Wallis test. Multiple regression analysis was used to investigate which clinicopathological factors significantly affected SUVmax in each cancer type. RESULTS: The SUVmax correlated with glucose transporter-1 (GLUT-1) expression in NSCLC (r=0.536, P=0.007) and ESCC (r=0.597, P<0.001) but not in PTC. The SUVmax correlated with Ki-67 expression in NSCLC (r=0.381, P=0.022) and PTC (r=0.374, P=0.017) but not in ESCC. A high SUVmax was correlated with a higher pathological T stage (p-T stage) in NSCLC (r=0.536) and ESCC (r=0.597, both P<0.001) but not in PTC. An elevated SUVmax was significantly associated with pathological lymph node status (p-N) in NSCLC, but not in ESCC and PTC. In multiple regression analysis, p-T stage and GLUT-1 expression were statistically significant factors in ESCC, and p-T stage was a statistically significant factor in NSCLC. In PTC, Ki-67 showed a statistically significant association with SUVmax. CONCLUSION: SUVmax in NSCLC depended on the tumor invasion area; SUVmax in ESCC depended on tumor depth and GLUT-1 expression; and SUVmax in PTC might be associated with cell proliferation. The biological factors affecting SUVmax differ according to tumor type.

The relationship between 18F-FDG metabolic volumetric parameters and clinicopathological factors of breast cancer.

OBJECTIVES: This study was conducted to evaluate the relationship between fluorine-18 fluorodeoxyglucose metabolic parameters [maximum standardized uptake value (SUV(max)), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] and clinicopathological factors of breast cancer. METHODS: The study comprised 93 patients. A volumetric region of interest was drawn over the abnormal focal uptake of breast cancer. Spearman's rank correlation, the Kruskal-Wallis test, and receiver operating characteristic analysis were used to investigate the relationship between clinicopathological factors and metabolic parameters and determine which metabolic parameters were most highly associated with clinicopathological factors. RESULTS: All parameters had a statistically significant relationship with pathological T stage (p-T stage), pathological N status (p-N status), pathological stage (p-stage), and triple-negative type (TN) (all P values were <0.05). There were statistically significant differences between SUV(max) and TLG in relation to lymphatic invasion, estrogen receptor, and nuclear grade (P<0.05). High MTV showed a tendency toward association with estrogen receptor negativity, but the relation did not reach the level of statistical significance (P=0.056). No statistically significant relationship was observed between MTV and lymphatic invasion or nuclear grade. In the receiver operating characteristic analysis of p-T stage and p-stage, the AUC for TLG was significantly larger than that for SUV(max) (P=0.0003 and 0.048, respectively). There were marginally significant differences between TLG and MTV in relation to p-stage (P=0.058). CONCLUSION: TLG may reflect tumor metabolism for clinicopathological factors of breast cancer better than SUV(max) or MTV.

18F-FDG uptake in primary gastric malignant lymphoma correlates with glucose transporter 1 expression and histologic malignant potential.

Positron emission tomography (PET) is used for staging and response evaluation in primary gastric lymphoma (PGL). However, the implications of [(18)F]-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) uptake in PGL at first diagnosis have not been reported. The relationship between (18)F-FDG uptake and the expression of facilitative glucose transporters (GLUTs), hexokinase II (HK II), and Ki67, as well as malignant potential in PGL, was assessed in this study. We analyzed 23 patients with PGL [nine with diffuse large B-cell lymphoma (DLBCL); seven with high-grade mucosa-associated lymphoid tissue (MALT) lymphoma; and seven with low-grade MALT lymphoma]. The expression levels of GLUT1, GLUT3, HK II, and Ki67 were evaluated according to the percentage of positive area determined by immunohistochemistry. Standardized uptake values correlated significantly with pathological malignant potentials (low-grade/high-grade MALT lymphoma and DLBCL: p = 0.001-0.002), Ki67 (p < 0.001), and GLUT1 expression (p = 0.02). We determined that (18)F-FDG uptake is related to GLUT1 expression and tumor histological grade as well as Ki67 in PGL.

Incidental detection of rare mesenteric inflammatory pseudotumor by (18)F-FDG PET.

A 60 years old asymptomatic male underwent fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) for his medical check-up, and abnormal (18)F-FDG uptake was observed in the retroperitoneum. The maximum standardized uptake value (SUV (max)) was 5.2. Based on CT, MRI and (18)F-FDG PET findings, the differential diagnosis included specific or non-specific inflammatory change, malignant lymphoma, trauma, gastrointestinal stromal tumor and soft-tissue sarcoma. Tumor resection was performed, and the histopathological finding was an inflammatory pseudotumor (IPT) originating at the mesentery in the retropetonium. After two years and eight months from his initial operation, recurrent IPT was detected by (18)F-FDG PET for follow-up, although he was asymptomatic. The IPT could be of traumatic origin since the patient suffered a severe abdominal trauma 6 months before. A mesenteric IPT is very rare, and to our knowledge, this is the first case report of (18)F-FDG PET detecting a mesenteric IPT. In conclusion, when abnormal high (18)F-FDG uptake is observed in the mesentery incidentally in clinical routine examination, IPT should be included as one of the differential diagnoses. (18)F-FDG may be useful in detecting local recurrence and follow-up after operation.

The relationship between GLUT-1 and vascular endothelial growth factor expression and 18F-FDG uptake in esophageal squamous cell cancer patients.

PURPOSE: To examine the relationship between glucose transporter-1 (GLUT-1) and vascular endothelial growth factor (VEGF) expression and (18)F-FDG uptake in esophageal squamous cell cancer patients. MATERIALS AND METHODS: Fifty-seven patients (52 male and 5 female) were included in this study. (18)F-FDG PET/CT was performed prior to the surgery. Immunohistochemistry was performed using postoperative histopathological specimens. The estimation of immunohistochemistry was conducted using scoring analysis. We investigated the correlations between maximum standardized uptake value (SUV(max)) and GLUT-1/VEGF expressions/pathologic tumor length (p-tumor length), and the relationships between pathologic T (p-T) stage and GLUT-1/VEGF expressions/SUV(max) and between lymph node metastasis (p-N) stage and GLUT-1/VEGF expressions/SUV(max). RESULTS: SUV(max) significantly correlated with GLUT-1 expressions and p-tumor length (GLUT-1: r = 0.475, P < 0.001; p-tumor length: r = 0.475, P < 0.001). SUV(max) of the primary tumor had a significant relationship with p-T stage, p-N stage, and VEGF expression (p-T stage: P < 0.001; p-N stage: P = 0.037; VEGF expression: P = 0.009). There was a statistically significant difference between GLUT-1 expression and p-T stage/VEGF expression, but not p-N stage (p-T stage: P = 0.012; VEGF expression: P = 0.01; p-N stage: P = 0.572). VEGF expression had a significant relationship with p-T stage, but not with p-N stage (p-T stage: P = 0.032; p-N stage: P = 0.763). CONCLUSION: (18)F-FDG uptake can be determined by GLUT-1 and VEGF. SUV(max) would have a connection with the tumor progression and lymph node metastasis.

Comparison between endoscopic macroscopic classification and F-18 FDG PET findings in gastric mucosa-associated lymphoid tissue lymphoma patients.

PURPOSE: The aim of this study was to compare endoscopic macroscopic classification with fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to investigate the usefulness of F-18 FDG positron emission tomography (PET) for diagnosing gastric MALT lymphoma. MATERIALS AND METHODS: Sixteen patients with gastric MALT lymphoma who underwent F-18 FDG PET and gastrointestinal imaging modalities were included in this study. Sixteen healthy asymptomatic participants undergoing both F-18 FDG PET and endoscopy for cancer screening were in the control group. We investigated the difference of F-18 FDG uptake between the gastric MALT lymphoma and the control group and compared the uptake pattern in gastric MALT lymphoma with our macroscopic classification. RESULTS: The endoscopic findings of 16 gastric MALT lymphoma patients were classified macroscopically as chronic gastritis-like tumors (n = 6), depressed tumors (n = 5), and protruding tumors (n = 5). Abnormal gastric F-18 FDG uptake was observed in 63% of tumors in the gastric MALT lymphoma group and 50% of cases in the control group. The median maximum standardized uptake values for gastric MALT lymphoma patients and control group were 4.0 and 2.6, respectively, the difference of which was statistically significant (P = 0.003). F-18 FDG uptake results were positive for all protruding tumors but only 50% for chronic gastritis-like tumors and 40% for depressed-type tumors. CONCLUSIONS: F-18 FDG PET may be a useful method for evaluating protrusion-type gastric MALT lymphoma. When strong focal or diffuse F-18 FDG uptake is detected in the stomach, endoscopic biopsy should be performed, even if the endoscopic finding is chronic gastritis.

Utility of multidetector row CT in diagnosing branch duct IPMNs of the pancreas compared with MR cholangiopancreatography and endoscopic ultrasonography.

This study aimed to compare the usefulness of multidetector row CT (MDCT), MR cholangiopancreatography (MRCP), and endoscopic ultrasonography (EUS) in diagnosing branch duct intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Imaging and pathological findings were retrospectively evaluated for 25 patients with branch duct IPMNs of the pancreas who underwent surgical resection (13 adenomas, 4 borderline lesions, and 8 carcinomas). MDCT and MRCP were performed on all 25 patients, whereas EUS was performed on 22 patients. MDCT and MRCP were used to identify features predictive of malignancy, including carcinoma, borderline lesions, and the presence of thickened irregular walls/septa or a solid mass. EUS was used to identify the presence of intramural nodules or a solid mass. Correlations between histopathology and maximum diameter of the main pancreatic duct (MPD) or cyst size detected by MDCT and MRCP were also examined. Presence of a solid mass was highly correlated with malignancy with all imaging methods (MDCT; P=0.001, MRCP; P=0.008, EUS; P<0.001, respectively). Presence of thickened irregular walls/septa on MDCT correlated well with malignancy (P=0.019). In contrast, presence of thickened irregular walls/septa on MRCP and intramural nodules on EUS did not correlate with malignancy. No significant correlation was found between malignancy and average maximum MPD diameter or cyst size (P>0.05), though values tended to be larger in malignant tumors. Our results suggest that the presence of thickened irregular walls/septa or a solid mass on MDCT are highly correlated with malignancy, and that MDCT is useful for diagnosis of branch duct IPMNs of the pancreas.

Glucose transporter expression of intraductal papilloma of the breast detected by fluorodeoxyglucose positron emission tomography.

A 40-year-old woman discovered through palpation a tumor in the upper lateral quadrant of the left mammary gland. Mammography, ultrasonography (US), and magnetic resonance imaging (MRI) showed a 10 mm diameter tumor. Fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) showed abnormal accumulation in the detected tumor, and the maximum standardized uptake value was 2.2. The patient underwent tumor resection. The postoperative histopathological finding was intraductal papilloma. The intraductal papilloma showed strong expression of glucose transporter (GLUT)-4 on membrane and/or cytoplasm, and weak expression of GLUT-1 and GLUT-3 by immunohistochemistry. This case suggests that other glucose transporters (e.g., GLUT-4), other pathological factors, and cytokines may have a close relation with (18)F-FDG accumulation in intraductal papilloma more than GLUT-1 or GLUT-3 expression.

Preliminary study of positron emission tomography/computed tomography and plasma osteopontin levels in patients with asbestos-related pleural disease.

PURPOSE: The aim of this study was to compare the results of semiquantitative analysis by(18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) with plasma osteopontin levels in the same asbestos-related pleural disease population. MATERIALS AND METHODS: A total of 17 patients with asbestos-related pleural disease were prospectively recruited. They underwent PET/CT, and plasma osteopontin levels were measured. The maximum standardized uptake value (SUVmax) was determined from the most active pleural lesion in each patient. RESULTS: Malignant pleural mesothelioma (MPM) was histologically proven in 6 patients, and 11 patients had proven benign asbestos-related pleural diseases (7 pleural plaques, 4 asbestos pleurisy). Significant differences in SUVmax were found between patients with MPM and those with asbestos pleurisy (P = 0.031) and between patients with MPM and those with pleural plaques (P = 0.012). A significant difference was found in the plasma osteopontin levels between patients with asbestos pleurisy and patients with pleural plaques (Bonferroni correction, P = 0.024). The SUVmax in patients with benign asbestos-related diseases was statistically positively correlated with plasma osteopontin in the same group (Spearman's r = 0.75, P < 0.05). CONCLUSION: PET/CT might be more helpful than plasma osteopontin for distinguishing benign asbestos-related pleural diseases from MPM, and the SUVmax in benign asbestos-related pleural diseases may reflect changes in pleural inflammation.

Glucose transporter expression of an esophageal gastrointestinal tumor detected by F-18 FDG PET/CT.

A 74-year-old woman had dysphagia and underwent esophagogastroduodenoscopy. A giant submucosal tumor was seen from the middle to the lower esophagus. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG-PET/CT) was performed and F-18 FDG was found to accumulate in the submucosal tumor. The maximum standardized uptake value of the early phase was 4.93 and that of the delayed phase was 6.48. Gastrointestinal stromal tumor (GIST) was confirmed by both fine needle aspiration under endoscopic ultrasound and postoperative histopathologic findings. We stained the postoperative histopathologic specimen to investigate glucose transporter (GLUT) expression using immunohistochemistry, which revealed that GLUT-1 had a weak expression on membranes and GLUT-4 had a strong expression on membranes or in cytoplasm. GLUT-3 had no expression on membranes or in cytoplasm. Esophageal GIST is rare and the relationship between GLUT expression and F-18 FDG accumulation in GIST is probably rare.

Coil embolization of splenic artery aneurysm with preservation of the parent artery using a neck remodeling technique.

We describe a case of a large and wide neck splenic artery aneurysm, treated by coil embolization using a balloon neck remodeling technique. The patency of the splenic artery was preserved without technical complications. This method should be considered as an alternative method for transcatheter management of splenic artery aneurysms.