Functional connectivity between the amygdala and subgenual cingulate gyrus predicts the antidepressant effects of ketamine in patients with treatment-resistant depression.

AIM: Approximately one-third of patients with major depressive disorder develop treatment-resistant depression. One-third of patients with treatment-resistant depression demonstrate resistance to ketamine, which is a novel antidepressant effective for this disorder. The objective of this study was to examine the utility of resting-state functional magnetic resonance imaging for the prediction of treatment response to ketamine in treatment-resistant depression. METHODS: An exploratory seed-based resting-state functional magnetic resonance imaging analysis was performed to examine baseline resting-state functional connectivity differences between ketamine responders and nonresponders before treatment with multiple intravenous ketamine infusions. RESULTS: Fifteen patients with treatment-resistant depression received multiple intravenous subanesthetic (0.5 mg/kg/40 minutes) ketamine infusions, and nine were identified as responders. The exploratory resting-state functional magnetic resonance imaging analysis identified a cluster of significant baseline resting-state functional connectivity differences associating ketamine response between the amygdala and subgenual anterior cingulate gyrus in the right hemisphere. Using anatomical region of interest analysis of the resting-state functional connectivity, ketamine response was predicted with 88.9% sensitivity and 100% specificity. The resting-state functional connectivity of significant group differences between responders and nonresponders retained throughout the treatment were considered a trait-like feature of heterogeneity in treatment-resistant depression. CONCLUSION: This study suggests the possible clinical utility of resting-state functional magnetic resonance imaging for predicting the antidepressant effects of ketamine in treatment-resistant depression patients and implicated resting-state functional connectivity alterations to determine the trait-like pathophysiology underlying treatment response heterogeneity in treatment-resistant depression.

Prognostic value of dual-point fluorine-18 fluorodeoxyglucose PET imaging, partial volume correction and glucose transporter-1 expression in resected nonsmall cell lung cancer patients.

OBJECTIVE: To investigate the relationship between the prognosis and glucose transporter-1 (Glut-1) expression or fluorine-18 fluorodeoxyglucose uptake using partial volume correction and dual-point imaging in surgically resected nonsmall cell lung cancer (NSCLC) patients. METHODS: Our patient population consisted of 108 NSCLC cases. The early maximum standardized uptake value (ESUVmax), delayed SUVmax (DSUVmax), partial volume correction SUVmax (cSUVmax) and retention index of primary lesions were calculated. Cox proportional hazard model was applied to evaluate the effects of PET parameters and Glut-1 expression. Overall survival (OS) and disease-free survival (DFS) were evaluated by Kaplan-Meier methods, and the difference in survival between subgroups was analyzed by log-rank test. RESULTS: On the Cox regression analysis, ESUVmax, DSUVmax, cSUVmax and Glut-1 were significantly related to DFS [ESUVmax, hazard ratio = 2.301, 95% confidential interval (CI) = 1.146-4.618, P = 0.019; DSUVmax, hazard ratio = 2.483, 95% CI = 1.257-4.905, P = 0.009; cSUVmax, hazard ratio = 2.205, 95% CI = 1.038-4.686, P = 0.04; Glut-1, hazard ratio = 2.095, 95% CI = 1.086-4.041, P = 0.001] and OS (ESUVmax, hazard ratio = 3.197, 95% CI = 1.339-7.633, P = 0.009; DSUVmax, hazard ratio = 3.599, 95% CI = 1.521-8.516, P = 0.004; cSUVmax, hazard ratio = 8.655, 95% CI = 2.048-36.658, P = 0.003; Glut-1, hazard ratio = 2.427, 95% CI = 5.140, P = 0.021). Retention index had no significant association with DFS or OS. On the Kaplan-Meier survival curves, the patients with high ESUVmax, DSUVmax, cSUVmax and Glut-1 showed significantly worse prognosis than those with low values (ESUVmax: DFS, P = 0.001, OS, P = 0.003; DSUVmax: DFS, P = 0.002, OS, P = 0.004; cSUVmax: DFS, P < 0.001, OS, P = 0.013; Glut-1: DFS, P = 0.012, OS, P = 0.002). CONCLUSIONS: cSUVmax, ESUVmax, DSUVmax and Glut-1 may be more useful biomarkers than retention index for predicting outcomes in NSCLC patients.

The assessment of correlation and prognosis among 18F-FDG uptake parameters, Glut1, pStat1 and pStat3 in surgically resected non-small cell lung cancer patients.

INTRODUCTION: To assess the correlation among 18F-FDG uptake, Glut1, pStat1 and pStat3, and to investigate the relationship between the prognosis and 18F-FDG uptake and these molecular markers in surgically resected non-small cell lung cancer (NSCLC) patients. RESULTS: Knockdown of Glut1 led to a significant increase in pStat1 expression. Glut1 expression positively correlated with the SUVmax, SUVmean, and TLG significantly (P<0.001). pStat3 expression negatively correlated with all PET parameters significantly (P<0.001). pStat1 had positive weak correlations with the SUVmax and SUVmean. All PET parameters and Glut1 were significantly associated with DFS (P<0.05). TLG, MTV, Glut1 and pStat1 were significantly associated with OS (P<0.05). CONCLUSION: pStat3 and Glut1 may be associated with 18F-FDG uptake mechanism. TLG, MTV, and Glut1 may be independent prognostic factors. METHODS: The SUVmax, SUVmean, MTV and TLG of primary lesions were calculated in 140 patients. The expressions of Glut1 and Stat pathway proteins in NSCLC cell lines were examined by immune blots. Excised tumor tissue was analyzed by immunohistochemistry. OS and DFS were evaluated by the Kaplan-Meier method. The difference in survival between subgroups was analyzed by log-rank test. The prognostic significance of clinicopathological, molecular and PET parameters was assessed by Cox proportional hazard regression analysis.

Correlations between dual-phase 18F-FDG uptake and clinicopathologic and biological markers of breast cancer.

OBJECTIVE: To assess the correlations between dual-phase fluorine-18 fluorodeoxyglucose (18F-FDG) uptake and clinicopathological and immunohistochemical prognostic factors in patients with surgically resected breast cancer. SUBJECTS AND METHODS: We retrospectively analyzed the cases of 105 patients. We calculated the maximum standardized uptake value (SUVmax) at 85min (SUV1), SUVmax at 125min (SUV2) and the retention index [RI]. Spearman's rank correlation test, the Kruskal-Wallis test and receiver operating characteristic (ROC) analysis were performed to assess the association between 18F-FDG uptake and the clinicopathological and immunohistochemical factors: glucose transporter-1 (Glut-1), estrogen receptor alpha (ERα), ERß, progesterone receptor (PR), human epidermal growth factor 2 (Her2), mammalian target of rapamycin (mTOR), and P70S6kinase (P70S6). RESULTS: The SUV1 and SUV2 values were correlated with Glut-1, pathological tumor size, ERα negativity, and pathological stage (all P values were <0.05), but not with mTOR, P70S6, ERß, PR, Her2 or other factors. The SUV1 and SUV2 in the triple negative subtype were significantly higher than those of the hormone receptor-positive subtype (P<0.05). The RI was associated with pathological tumor size alone. In the ROC analysis of Glut-1, the areas under the curve for SUV1 and SUV2 were significantly larger than that for RI (SUV1, P=0.032, SUV2, P=0.022). CONCLUSION: Glucose transporter-1, estrogen receptor alpha negativity and nuclear grade might affect the high 18F-FDG uptake in breast cancer. The SUVmax might be more useful than the RI for predicting the Glut-1 expression and the aggressiveness of breast cancer.

Tumoricidal effect and pain relief after concurrent therapy by strontium-89 chloride and zoledronic acid for bone metastases.

OBJECTIVE: The purpose of this study was to investigate the palliative and tumoricidal effects of concurrent therapy of strontium-89 chloride (89SrCl2) and zoledronic acid (ZA) for painful bone metastases. SUBJECTS AND METHODS: Fifty-one patients with painful bone metastases prostate cancer (n=17), lung cancer (n=13), breast cancer (n=12), other cancers (n=9) were treated. Bone metastases was confirmed in all patients by technetium-99m hydroxymethylene diphosphonate (99mTc-HMDP) bone scintigraphy. The numeric rating scale (NRS) and performance status (PS) were used to assess the degree of pain and patients' physical condition. The extent of bone metastases was assessed with imaging modalities including CT, MRI and/or 99mTc bone scintigraphy before treatment and 2 or 3 months after. RESULTS: The pain relief response of 89SrCl2 with ZA for bone metastases was 94% (48/51) from 1 to 3 months after treatment. The tumoricidal effect of concurrent therapy by 89SrCl2 with ZA for painful bone metastases was 8/22 as shown by imaging modalities and the rate of non-progressive disease (non-PD) was 19/22. Pain due to bone metastases assessed with the NRS was significantly improved (P<0.001) in many types of primary cancer, including prostate, breast and lung cancers. CONCLUSION: Concurrent therapy of 89SrCl2 with ZA may offer not only pain relief, but also a tumoricidal effect for painful bone metastases.

The correlation between FDG uptake and biological molecular markers in pancreatic cancer patients.

PURPOSE: We examined whether fluorine-18 fluorodeoxyglucose (FDG) uptake is related to the mammalian target of rapamycin (mTOR) signal pathway and its related proteins in pancreatic cancer patients. METHODS: We retrospectively studied 53 pancreatic cancer patients who underwent FDG positron emission tomography (PET) or FDG PET/CT, and complete curative surgical resection. The SUV max, the tumor to nontumor activity of pancreas [T/N (P)] ratio and the T/N of liver [T/N (L)] ratio were calculated. The expressions of glucose transporter-1(Glut-1) and mTOR pathway proteins in pancreas cell lines were examined by immune blots. Excised tumor tissue was analyzed by immunohistochemistry using monoclonal antibodies for Glut-1, epidermal growth factor receptor (EGFR), mTOR, p70S6kinase (p70S6) and S6 ribosomal protein (S6). RESULTS: The expressions of Glut-1, EGFR and p70S6 were significantly correlated with the SUV max, T/N (P) ratio and T/N (L) ratio. The expressions of mTOR and S6 were not correlated with all parameters. The expression of Glut-1 was positively correlated with the expressions of EGFR and p70S6, but not with mTOR or S6. S6 was positively correlated with p70S6. CONCLUSIONS: Glut-1, EGFR and p70S6 expressions are associated with the FDG uptake mechanism of pancreatic cancer. FDG uptake may predict the levels of EGFR and p70S6 expressions, and FDG uptake reflects glucose metabolism and cancer progression.

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.

Altered SPECT (123)I-iomazenil Binding in the Cingulate Cortex of Children with Anorexia Nervosa.

Several lines of evidence suggest that anxiety plays a key role in the development and maintenance of anorexia nervosa (AN) in children. The purpose of this study was to examine cortical GABA(A)-benzodiazepine receptor binding before and after treatment in children beginning intensive AN treatment. Brain single-photon emission computed tomography (SPECT) measurements using (123)I-iomazenil, which binds to GABA(A)-benzodiazepine receptors, was performed in 26 participants with AN who were enrolled in a multimodal treatment program. Sixteen of the 26 participants underwent a repeat SPECT scan immediately before discharge at conclusion of the intensive treatment program. Eating behavior and mood disturbances were assessed using Eating Attitudes Test with 26 items (EAT-26) and the short form of the Profile of Mood States (POMS). Clinical outcome scores were evaluated after a 1-year period. We examined association between relative iomazenil-binding activity in cortical regions of interest and psychometric profiles and determined which psychometric profiles show interaction effects with brain regions. Further, we determined if binding activity could predict clinical outcome and treatment changes. Higher EAT-26 scores were significantly associated with lower iomazenil-binding activity in the anterior and posterior cingulate cortex. Higher POMS subscale scores were significantly associated with lower iomazenil-binding activity in the left frontal, parietal cortex, and posterior cingulate cortex (PCC). "Depression-Dejection" and "Confusion" POMS subscale scores, and total POMS score showed interaction effects with brain regions in iomazenil-binding activity. Decreased binding in the anterior cingulate cortex and left parietal cortex was associated with poor clinical outcomes. Relative binding increases throughout the PCC and occipital gyrus were observed after weight gain in children with AN. These findings suggest that cortical GABAergic receptor binding is altered in children with AN. This may be a state-related change, which could be used to monitor and guide the treatment of eating disorders.

Assessment of cell proliferation in renal cell carcinoma using dual-phase 18F-fluorodeoxyglucose PET/CT.

The present study aimed to examine the association between 18F-fluorodeoxyglucose (18F-FDG) uptake and cell proliferation markers; in addition, the correlation between 18F-FDG uptake and biological characteristic in patients with renal cell carcinoma (RCC) was investigated using dual-phase 18F-FDG-positron emission tomography/computed tomography (PET/CT). Dual-phase 18F-FDG PET/CT was performed on 31 RCC patients and the maximum standardized uptake values at 1 h (SUV1) and 2 h (SUV2) as well as the retention index (RI; %) in the primary tumors were calculated. Monoclonal antibodies for Ki-67, minichromosome maintenance 2 (MCM2) and topoisomerase II α (topo II α) were used to assess the expression levels of their respective proteins in excised tumor tissue using immunohistochemistry. The results demonstrated that RI and SUV2 in patients with Stage I/II + grade 1 (G1) RCC were significantly decreased compared with all patients with other stages/grades (RI, P=0.0065; SUV2, P=0.043); in addition, significantly increased uptake and RI were detected in patients with metastases compared with patients without metastases (SUV1, P=0.029; SUV2, P=0.0003; RI, P<0.001). All proliferation markers significantly correlated with RI (Ki-67, r=0.501, P=0.004; MCM2, r=0.359, P=0.047; topo II α, r=0.402, P=0.024), while SUV1 and SUV2 correlated with Ki-67 only. In conclusion, the results of the present study demonstrated that dual-phase 18F-FDG-PET/CT was more useful for predicting cell proliferation in RCC compared with single-phase imaging alone. However, follow-ups are required in order to determine whether dual-phase 18F-FDG-PET/CT provides independent prognostic information.

¹8F-FDG PET/CT and contrast enhanced CT in differential diagnosis between leiomyoma and gastrointestinal stromal tumor.

In a 49 years old woman a large abdominal tumor was diagnosed by abdominal ultrasound. Dynamic contrast-enhanced computed tomography (CECT) showed a large tumor with minute calcification and poor contrast enhancement in the left abdominal cavity. The fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (¹8F-FDG PET/CT) scan showed low ¹8F-FDG uptake in the tumor. The SUV max (early image) was 1.90, and that of the delayed image was 2.86. A gastrointestinal stromal tumor (GIST) was suspected. Tumor resection revealed that it was a leiomyoma originating in the major curvature of the stomach. In conclusion, the findings of low ¹8F-FDG uptake on ¹8F-FDG PET and poor contrast enhancement on CECT in a gastric submucosal tumor suggested of a gastric leiomyoma rather than GIST.

Upregulated GABA Inhibitory Function in ADHD Children with Child Behavior Checklist-Dysregulation Profile: 123I-Iomazenil SPECT Study.

The child behavior checklist-dysregulation profile (CBCL-DP) refers to a pattern of elevated scores on the attention problems, aggression, and anxiety/depression subscales of the child behavior checklist. The aim of the present study was to investigate the potential role of GABA inhibitory neurons in children with attention deficit/hyperactivity disorder (ADHD) and dysregulation assessed with a dimensional measure. Brain single photon emission computed tomography (SPECT) was performed in 35 children with ADHD using 123I-iomazenil, which binds with high affinity to benzodiazepine receptors. Iomazenil binding activities were assessed with respect to the presence or absence of a threshold CBCL-DP (a score ≥210 for the sum of the three subscales: Attention Problems, Aggression, and Anxiety/Depression). We then attempted to identify which CBCL-DP subscale explained the most variance with respect to SPECT data, using "age," "sex," and "history of maltreatment" as covariates. Significantly higher iomazenil binding activity was seen in the posterior cingulate cortex (PCC) of ADHD children with a significant CBCL-DP. The Anxiety/Depression subscale on the CBCL had significant effects on higher iomazenil binding activity in the left superior frontal, middle frontal, and temporal regions, as well as in the PCC. The present brain SPECT findings suggest that GABAergic inhibitory neurons may play an important role in the neurobiology of the CBCL-DP, in children with ADHD.

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.

Positive correlation between malondialdehyde-modified low-density lipoprotein cholesterol and vascular inflammation evaluated by 18F-FDG PET/CT.

OBJECTIVE: The purpose of this study was to investigate the relationship between serum levels of malondialdehyde-modified low-density lipoprotein cholesterol (MDA-LDL) and vascular inflammation evaluated by fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT). METHODS/RESULTS: The study involved 106 consecutive patients (75 males and 31 female, mean age 62.5 ± 7.7 years) who visited our hospital for cardiovascular risk screening and underwent carotid ultrasonography, (18)F-FDG PET/CT, complete history, physical examinations, and determination of blood chemistry including high-sensitivity C-reactive protein (hsCRP), asymmetric dimethylarginine (ADMA), and MDA-LDL. Vascular inflammation, was measured as blood-normalized standardized (18)F-FDG uptake value, known as the target-to-background ratio (TBR) of carotid arteries. Univariate and multiple stepwise regression analyses were performed for determining independent correlates of carotid TBR values. Median MDA-LDL, mean carotid TBR values and carotid intima-media thickness (IMT) were 127.5 (IQR 92.0-147.8) U/l, 1.55 ± 0.22, and 0.72 ± 0.15 mm, respectively. Univariate analysis revealed that carotid TBR values positively correlated with MDA-LDL (p = 0.043) and carotid IMT (p = 0.049). Multiple stepwise regression analysis demonstrated that MDA-LDL (p = 0.043) and carotid IMT (p = 0.038) were independently associated with carotid TBR values. CONCLUSION: The present study reveals that serum levels of MDA-LDL are independently associated with vascular inflammation evaluated by (18)F-FDG PET/CT. Circulating MDA-LDL may be a more useful clinical biomarker for vascular inflammation within the atherosclerotic plaques than hsCRP or ADMA.

Maximum standardized uptake value on 18F-fluoro-2-deoxy-glucose positron emission tomography/computed tomography and glucose transporter-1 expression correlates with survival in invasive ductal carcinoma of the pancreas.

OBJECTIVES: The purpose of this study was to assess the correlations among the maximum standardized uptake value (SUVmax) on 18F-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT); the expressions of glucose transporter 1 (GLUT-1), glucose transporter 3, and epidermal growth factor receptor (EGFR); as well as prognosis in patients with invasive ductal carcinoma of the pancreas. METHODS: A total of 41 patients with surgically resected and histologically proven invasive ductal carcinoma of the pancreas who underwent preoperative FDG-PET/CT were assessed. The SUVmax at the primary tumor site was measured by FDG-PET/CT, and immunohistochemical staining of tumor sections was performed for GLUT-1, glucose transporter 3, and EGFR. RESULTS: Higher FDG uptake (SUVmax, >3.40) and GLUT-1 expression were significantly associated with shorter overall survival (P < 0.05). The SUVmax was not found to be significantly correlated with clinicopathological characteristics such as TNM classification, lymph node metastasis, and tumor differentiation. The EGFR expression was significantly correlated with the SUVmax (P = 0.024). CONCLUSIONS: Higher FDG uptake and GLUT-1 expression in invasive ductal carcinoma of the pancreas seems to be an important prognostic factor. In addition, the EGFR expression was significantly correlated with the SUVmax.

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.

A serial ¹8FDG-PET study of a patient with SSPE who had good prognosis by combination therapy with interferon alpha and ribavirin.

We describe a 15-year-old girl with subacute sclerosing panencephalitis (SSPE) in stage II who was treated with isoprinosine, intraventricular interferon alpha (IFN-α), and ribavirin for 3 years. She is alive at three years from onset and studies at school with the assistance of a special educational teacher. To assess residual brain function, serial (18)FDG-positron emission tomography (PET) was performed three times to measure cortical metabolism: at onset, a year later, and three years later. At onset, PET study revealed preserved glucose metabolism of the cerebral cortex. In serial PET study, glucose metabolism of the cerebral cortex was also preserved even after three years. Although SSPE is a progressive disease of the neuronal system, and typically leads to death in approximately 2-3 years, the neurological prognosis of our case was good. We consider that combination therapy in the very early stage without hypometabolism in the cerebral cortex may be effective for SSPE.

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.

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.