Hayato Kaida

Heterogeneous myocardial FDG uptake and the disease activity in cardiac sarcoidosis.

OBJECTIVES This study evaluated the usefulness of fasting (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in the diagnosis and management of cardiac sarcoidosis (CS) and compared it with FDG uptake in dilated cardiomyopathy (DCM). BACKGROUND Cardiac sarcoidosis may clinically present as DCM but is amenable to systemic corticosteroid therapy if disease activity is high. Although alterations of FDG uptake have been reported in CS, limited information is available on the quantitative estimates of FDG uptake. METHODS Fasting FDG-PET was performed in 24 systemic sarcoidosis patients and was compared with 8 age-matched DCM patients. FDG-PET was also performed in 15 age-matched healthy control subjects. Twelve of the 24 sarcoidosis patients had cardiac involvement based on criteria established by the Japanese Ministry of Health and Welfare; the remaining 12 of 24 patients revealed no evidence of cardiac involvement. The myocardial FDG uptake was quantified by measuring the standardized uptake value in 17 myocardial segments in each subject. Coefficient of variation (COV), which equals the standard deviation of uptake divided by the average uptake of 17 segments, was calculated as an index of heterogeneity in the heart. RESULTS The FDG uptake was distinctly heterogeneous in CS patients. The COV value was significantly greater in CS patients (0.25 ± 0.05) than control subjects (0.14 ± 0.03, p < 0.01), sarcoidosis patients without cardiac involvement (0.14 ± 0.03, p < 0.01), or DCM patients (0.15 ± 0.02, p < 0.01). The COV value in DCM patients was similar to control subjects or sarcoidosis patients without cardiac involvement. The cutoff COV value for the diagnosis of CS was 0.18 (sensitivity: 100%; specificity: 97%). After corticosteroid therapy in CS patients, the COV value was decreased to 0.14 ± 0.06 (p < 0.05) and became essentially similar to the other groups. CONCLUSIONS Heterogeneous myocardial FDG uptake may be a useful diagnostic marker of disease activity for CS.

Pioglitazone Attenuates Atherosclerotic Plaque Inflammation in Patients With Impaired Glucose Tolerance or Diabetes: A Prospective, Randomized, Comparator-Controlled Study Using Serial FDG PET/CT Imaging Study of Carotid Artery and Ascending Aorta

OBJECTIVES The aim of this study was to compare the effect of pioglitazone, an insulin sensitizer, with glimepiride, an insulin secretagogue, on atherosclerotic plaque inflammation by using serial (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. BACKGROUND Atherosclerosis is intrinsically an inflammatory disease. Although hyperglycemia is associated with an increased risk of atherosclerotic cardiovascular disease, there are no clinical data to show the preference of any specific oral hypoglycemic agents to prevent atherosclerotic plaque inflammation. METHODS A total of 56 impaired glucose tolerant or diabetic patients with carotid atherosclerosis underwent a complete history, determinations of blood chemistries, anthropometric variables, and FDG-PET. They were randomly assigned to receive either pioglitazone (15 to 30 mg) or glimepiride (0.5 to 4.0 mg) for 4 months with titration to optimal dosage. Effects of the drugs on atherosclerotic plaque inflammation were evaluated by FDG-PET at study completion. Plaque inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio. RESULTS The study was completed in 31 pioglitazone-treated patients and 21 glimepiride-treated patients. Although both treatments reduced fasting plasma glucose and hemoglobin A1c values comparably, pioglitazone, but not glimepiride, decreased atherosclerotic plaque inflammation. Compared with glimepiride, pioglitazone significantly increased high-density lipoprotein cholesterol level. High-sensitivity C-reactive protein was decreased by pioglitazone, whereas it was increased by glimepiride. Multiple stepwise regression analysis revealed that the increase in high-density lipoprotein cholesterol level was independently associated with the attenuation of plaque inflammation. CONCLUSIONS Our present study suggests that pioglitazone could attenuate atherosclerotic plaque inflammation in patients with impaired glucose tolerance or in diabetic patients independent of glucose lowering effect. Pioglitazone may be a promising strategy for the treatment of atherosclerotic plaque inflammation in impaired glucose tolerance or diabetic patients. (Detection of Plaque Inflammation and Visualization of Anti-Inflammatory Effects of Pioglitazone on Plaque Inflammation in Subjects With Impaired Glucose Tolerance and Type 2 Diabetes Mellitus by FDG-PET/CT; NCT00722631).

Positive Association Between Serum Level of Glyceraldehyde-Derived Advanced Glycation End Products and Vascular Inflammation Evaluated by [18F]Fluorodeoxyglucose Positron Emission Tomography

OBJECTIVE Advanced glycation end products (AGEs) evoke inflammatory reactions, contributing to the development and progression of atherosclerosis. We investigated the relationship between serum AGE level and vascular inflammation. RESEARCH DESIGN AND METHODS The study involved 275 outpatients at Kurume University, Japan (189 males and 86 females; mean age 61.2 ± 8.8 years) who underwent complete history and physical examinations and determinations of blood chemistry and anthropometric variables, including AGEs. Serum AGE level was examined by enzyme-linked immunosorbent assay. Vascular [18F]fluorodeoxyglucose (FDG) uptake, an index of vascular inflammation, was measured as blood-normalized standardized uptake value, known as the target-to-background ratio (TBR), by FDG–positron emission tomography (FDG-PET). Furthermore, we examined whether the changes in serum AGE level after treatment with oral hypoglycemia agents (OHAs) were correlated with those of TBR in another 18 subjects whose AGE value was >14.2 units/mL (mean ± 2 SD). RESULTS Mean serum AGE level and carotid TBR values were 9.15 ± 2.53 and 1.43 ± 0.22 units/mL, respectively. Multiple stepwise regression analysis revealed that TBR was independently correlated with AGEs (P < 0.001), carotid intima-media thickness (P < 0.01), and BMI (P < 0.02). When age- and sex-adjusted AGE values stratified by TBR tertiles were compared using ANCOVA, a significant trend was observed (P < 0.01). In addition, the changes in AGEs after OHA treatment were positively (r = 0.50, P < 0.05) correlated with those in TBR value. CONCLUSIONS The current study reveals that serum AGE level is independently associated with vascular inflammation evaluated by FDG-PET, suggesting that circulating AGE value may be a biomarker that could reflect vascular inflammation within an area of atherosclerosis.

Value of fusing PET plus CT images in hepatocellular carcinoma and combined hepatocellular and cholangiocarcinoma patients with extrahepatic metastases: preliminary findings.

Abstract: Background/Aims: This study aimed to evaluate the usefulness of 18F‐fluoro‐2‐deoxy‐d‐glucose positron emission tomography (PET) and PET plus computed tomography (CT) fusion images for the detection of extrahepatic metastases of hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (combined HCC/CC).

Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy

BACKGROUND [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET) imaging has been employed as a non-invasive diagnostic tool for malignant tumors. Total lesion glycolysis (TLG) on FDG-PET is calculated by multiplying the mean standardized uptake value (SUVmean) by the tumor volume. Unlike the maximum standardized uptake value (SUVmax), which represents the point of greatest metabolic activity within tumors, TLG has been suggested to reflect global metabolic activity in whole tumors. METHODS We retrospectively examined whether or not FDG-PET measurements, including SUVmean, SUVmax, and TLG, could predict progression-free survival (PFS) or overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. RESULTS This study involved 81 consecutive patients with NSCLC who received chemotherapy. All of the patients underwent FDG-PET examination before treatment. SUVmean, SUVmax, and TLG on FDG-PET were significantly associated with gender, smoking status, and tumor histology. With adjustment for several other variables, Cox regression analysis showed that TLG was significantly prognostic for both PFS [hazard ratio=2.34; 95% confidence interval, 1.18-4.64; P=0.015] and OS (hazard ratio=2.80; 95% confidence interval, 1.12-6.96; P=0.003), whereas SUVmean and SUVmax had no significant association with PFS (P=0.693 and P=0.322, respectively) or OS (P=0.587 and P=0.214, respectively). CONCLUSIONS Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting PFS and OS in NSCLC patients receiving chemotherapy. The TLG measurement on FDG-PET imaging could be routinely recommended to advanced NSCLC patients.

Pioglitazone Decreases Coronary Artery Inflammation in Impaired Glucose Tolerance and Diabetes Mellitus : Evaluation by FDG-PET/CT Imaging

OBJECTIVES The aim of this study was to compare the effect of pioglitazone with glimepiride on coronary arterial inflammation with serial (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT) angiography. BACKGROUND Recent studies have shown that FDG-PET combined with CT is a reliable tool to visualize and quantify vascular inflammation. Although pioglitazone significantly prevented the progression of coronary atherosclerosis and reduced the recurrence of myocardial infarction in patients with type 2 diabetes mellitus (DM), it remains unclear whether pioglitazone could attenuate coronary artery inflammation. METHODS Fifty atherosclerotic patients with impaired glucose tolerance or type 2 DM underwent determination of blood chemistries, anthropometric and inflammatory variables, and FDG-PET/CT angiography, and then were randomized to receive either pioglitazone or glimepiride for 16 weeks. Effects of the treatments on vascular inflammation of the left main trunk were evaluated by FDG-PET/CT angiography at baseline and end of the study. Vascular inflammation of the left main trunk was measured by blood-normalized standardized uptake value, known as a target-to-background ratio. RESULTS Three patients dropped out of the study during the assessment or treatment. Finally, 25 pioglitazone-treated patients and 22 glimepiride-treated patients (37 men; mean age: 68.1 ± 8.3 years; glycosylated hemoglobin: 6.72 ± 0.70%) completed the study. After 16-week treatments, fasting plasma glucose and glycosylated hemoglobin values were comparably reduced in both groups. Changes in target-to-background ratio values from baseline were significantly greater in the pioglitazone group than in the glimepiride group (-0.12 ± 0.06 vs. 0.09 ± 0.07, p = 0.032), as well as changes in high-sensitivity C-reactive protein (pioglitazone vs. glimepiride group: median: -0.24 [interquartile range (IQR): -1.58 to -0.04] mg/l vs. 0.08 [IQR: -0.07 to 0.79] mg/l, p = 0.031). CONCLUSIONS Our study indicated that pioglitazone attenuated left main trunk inflammation in patients with impaired glucose tolerance or DM in a glucose-lowering independent manner, suggesting that pioglitazone may protect against cardiac events in patients with impaired glucose tolerance or DM by suppressing coronary inflammation. (Anti-Inflammatory Effects of Pioglitazone; NCT00722631).

Effects of pioglitazone on visceral fat metabolic activity in impaired glucose tolerance or type 2 diabetes mellitus.

CONTEXT Excess visceral fat is associated with chronic systemic inflammation and cardiovascular complications. Pioglitazone has been reported to variably influence visceral fat volume; however, its effect on metabolic activity of the visceral fat remains uncharacterized. OBJECTIVE The aim of this study was to assess the effects of pioglitazone on glucose metabolism of fat tissue by using (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography imaging. DESIGN, SETTING, AND PARTICIPANTS FDG-PET and computed tomography imaging were performed in 56 patients with impaired glucose tolerance or type 2 diabetes mellitus; lipid and glycemic profiles and inflammatory biomarkers were obtained in all patients. These patients were randomized to treatment with either pioglitazone or glimepiride for 16 weeks. MAIN OUTCOME MEASURES The metabolic activity of the visceral fat tissues as assessed by FDG uptake was expressed as a target-to-background ratio (TBR) of blood-normalized standardized uptake value. RESULTS The study was completed in 32 pioglitazone-treated and 21 glimepiride-treated patients (40 men and 13 women; mean age, 67.7 ± 8.1 y; body mass index, 25.0 ± 3.6 kg/m(2); glycated hemoglobin, 6.78 ± 0.70%). Both treatments were well-tolerated and comparably improved glycemic control. At baseline, visceral fat exhibited a higher TBR value than subcutaneous fat (0.55 ± 0.14 vs 0.30 ± 0.07, P < .001). Pioglitazone, but not glimepiride, significantly decreased the visceral fat volume (130.5 ± 53.0 to 122.1 ± 51.0 cm(2), P = .013) and TBR values (0.57 ± 0.16 to 0.50 ± 0.11, P = .007). Neither pioglitazone nor glimepiride treatment showed any effect on the volume or TBR values of subcutaneous fat. After 16 weeks of treatment with pioglitazone, reduction in visceral fat TBR was correlated to the increase in high-density lipoprotein cholesterol levels. CONCLUSIONS Our study indicated that pioglitazone decreased the visceral fat volume and its metabolic activity in patients with impaired glucose tolerance or type 2 diabetes mellitus. The beneficial effects of pioglitazone on visceral fat may be independent of its glucose-lowering effect.

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 18F-FDG uptake in esophageal squamous cell cancer patients. Materials and Methods: Fifty-seven patients (52 male and 5 female) were included in this study. 18F-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 (SUVmax) 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/SUVmax and between lymph node metastasis (p-N) stage and GLUT-1/VEGF expressions/SUVmax. Results: SUVmax 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). SUVmax 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: 18F-FDG uptake can be determined by GLUT-1 and VEGF. SUVmax would have a connection with the tumor progression and lymph node metastasis.

Prognostic value of SUVmax measurements obtained by FDG-PET in patients with non-small cell lung cancer receiving chemotherapy.

[(18)F]Fluorodeoxyglucose (FDG) uptake has been shown to correlate well with tumor proliferation rates. In patients with non-small cell lung cancer (NSCLC) receiving chemotherapy, we analyzed the relationships between the maximum standardized uptake value (SUVmax) obtained by FDG positron emission tomography (FDG-PET) and other clinical factors, and examined whether or not SUVmax could predict progression-free survival (PFS) and/or overall survival (OS). This retrospective study involved 62 consecutive NSCLC patients (35 male and 27 female: median age, 65 years). All patients underwent FDG-PET examination before treatment. As the first-line treatment, the patients received chemotherapy with (n=15) or without (n=47) radiotherapy. Survival curves were obtained by the Kaplan-Meier method, and differences in survival between subgroups were analyzed by the log-rank test and the Cox proportional hazards model. Significant correlations were observed between SUVmax and gender (P=0.006), histology (P<0.001), smoking status (P=0.049), stage (P=0.015), and treatment modality (P=0.008), but not other factors, including age (P=0.402) and performance status (P=0.421). The median SUVmax was 5.1 (25-75th percentile: 3.45-7.0) in patients with adenocarcinoma and 8.3 (25-75th percentile: 6.9-9.9) in those with other types of NSCLC. Adenocarcinomas showed significantly lower SUVmax than the other tumor types (P<0.001). Cox analysis adjusting for possible confounding factors, including gender, smoking status, histology and stage, demonstrated that the hazard ratios increased as the SUVmax increased in terms of both PFS (P=0.008) and OS (P=0.045), indicating that SUVmax predicts outcome independently of other clinical factors, such as histology and stage. Our findings indicate that FDG-PET examination can provide information useful for prognostication in NSCLC.

Improved detection of breast cancer on FDG-PET cancer screening using breast positioning device

ObjectiveThe aim of this study was to investigate the detection rate of breast cancer by positron emission tomography cancer screening using a breast positioning device.MethodsBetween January 2004 and January 2006, 1,498 healthy asymptomatic individuals underwent cancer screening by fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) at our institution; 660 of 1498 asymptomatic healthy women underwent breast PET imaging in the prone position using the breast positioning device to examine the mammary glands in addition to whole-body PET imaging. All subjects that showed abnormal 18F-FDG uptake in the mammary glands were referred for further examination or surgery at our institution or a local hospital. Our data were compared with the histopathological findings or findings of other imaging modalities in our institution and replies from the doctors at another hospital.ResultsOf the 660 participants, 7 (1.06%) were found to have breast cancers at a curable stage. All the seven cancers were detected by breast PET imaging, but only five of these were detected by whole-body PET imaging; the other two were detected by breast PET imaging using the breast positioning device.ConclusionsIn cancer screening, prone breast imaging using a positioning device may help to improve the detection rate of breast cancer. However, overall cancer including mammography and ultrasonography screening should be performed to investigate the false-negative cases and reduce false-positive cases. The effectiveness of prone breast PET imaging in cancer screening should be investigated using a much larger number of cases in the near future.