Prognostic impact of LAT1 and CD98 expression in cutaneous angiosarcoma.

L-type amino acid transporter 1 (LAT1) and CD98 are frequently expressed in various human cancers, and closely correlated with tumor aggressiveness and survival. However, little is known about the expression of LAT1 and CD98 in cutaneous angiosarcoma. The aim of this study is to investigate the clinicopathological significance of these markers in the dismal disease. A total of 52 patients with cutaneous angiosarcoma were retrospectively reviewed. Immunohistochemical staining of tumor specimens were evaluated using anti-LAT1, CD98 and Ki-67 antibodies. The rates of high expression for LAT1 and CD98 were 56% (29/52) and 79% (41/52), respectively. The frequency of high expression for CD98 was significantly higher than that for LAT1 (p=0.021). The low expression of CD98 was significantly associated with distant metastasis (p=0.044) and was identified as a significant prognostic predictor by multivariate analysis. The expression level of LAT1 was not significantly correlated with prognosis. The low expression of CD98 is a novel biomarker for predicting poor prognosis in patients with cutaneous angiosarcoma.

GAD65/GAD67 double knockout mice exhibit intermediate severity in both cleft palate and omphalocele compared with GAD67 knockout and VGAT knockout mice.

Inhibitory neurotransmitters, γ-aminobutyric acid (GABA) and glycine, are transported into synaptic vesicles by the vesicular GABA transporter (VGAT). Glutamate decarboxylase (GAD) is a GABA-synthesizing enzyme and two isoforms of GAD, GAD65 and GAD67 are encoded by two independent genes. There was virtually no GABA content in GAD65/GAD67 double knockout (GADs DKO) mouse brains. Neither GABAergic nor glycinergic inhibitory postsynaptic currents were almost detected in VGAT knockout (KO) mouse cultured neurons and spinal cords. GAD67 KO and VGAT KO mice displayed developmental abnormalities, cleft palate and omphalocele, suggesting that GABAergic transmission is involved in palate and abdominal wall formations. However, the incidence and severity of both failures in GAD67 KO mice were lower and less than those in VGAT KO mice. These results raise the possibility that GABAergic transmission mediated by GAD65-produced GABA and/or glycinergic transmission contributed to both palate and abdominal wall formations. However, it still remains unclear whether GABAergic transmission mediated by GAD65 and glycinergic transmission contribute to those formations. Here, to answer these questions, we generated GADs DKO mice and compared the phenotypes of GADs DKO mice with those of GAD67 KO and VGAT KO mice. Our anatomical analyses demonstrated that the incidence of cleft palate and omphalocele in GAD67 KO mice was 65.8% and 58.9%, respectively, but the incidence of both phenotypes in GADs DKO and VGAT KO mice was 100%. The severity of cleft palate and omphalocele was evaluated by elevation of palate shelves and size and liver inclusion of omphalocele, respectively. We observed that the phenotypes of cleft palate and omphalocele in GADs DKO mice were more and less severe than those in GAD67 KO and VGAT KO mice, respectively. These results indicate the significant contribution of not only GAD65-mediated GABAergic but also glycinergic transmissions to both palate and abdominal wall formations.

Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer.

BACKGROUND: Amino-acid transporters are necessary for the tumour cell growth and survival, and have a crucial role in the development and invasiveness of cancer cells. But, it remains unclear about the prognostic significance of L-type amino-acid transporter 1 (LAT1), system ASC amino-acid transporter-2 (ASCT2), and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino-acid transporters in tongue cancer. METHODS: Eighty-five patients with surgically resected tongue cancer were evaluated. Tumour sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67, and microvessel density (MVD) determined by CD34, and p53. RESULTS: L-type amino-acid transporter 1 and 4F2hc were highly expressed in 61% (52 out of 85) and 45% (38 out of 47), respectively. ASC amino-acid transporter-2 and xCT were positively expressed in 59% (50 out of 85) and 21% (18 out of 85), respectively. The expression of both LAT1 and ASCT2 was significantly associated with disease staging, lymph-node metastasis, lymphatic permeation, 4F2hc expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumour factor. By univariate analysis, disease staging, lymphatic permeation, vascular invasion, LAT1, ASCT2, 4F2hc, and Ki-67 had a significant relationship with overall survival. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis. CONCLUSIONS: L-type amino-acid transporter 1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may have an important role in the development and aggressiveness of tongue cancer.

Biological significance of fluorine-18-α-methyltyrosine (FAMT) uptake on PET in patients with oesophageal cancer.

PURPOSE: (18)F-FAMT as an amino-acid tracer for positron emission tomography (PET) is useful for detecting human neoplasms. (18)F-FAMT is accumulated in tumour cells solely via L-type amino-acid transporter 1 (LAT1). This study was conducted to investigate the biological significance of (18)F-FAMT uptake in patients with oesophageal cancer. METHODS: From April 2008 to December 2011, 42 patients with oesophageal cancer underwent both (18)F-FAMT PET/CT and (18)F-FDG PET/CT before surgical treatment. The immunohistochemical analysis of LAT1, CD98, Ki-67, CD34, p53, p-Akt and p-mTOR was performed on the primary lesions. In vitro experiments were performed to examine the mechanism of (18)F-FAMT uptake. RESULTS: High uptake of (18)F-FAMT was significantly associated with advanced stage, lymph node metastasis and the expression of LAT1, CD98, Ki-67 and CD34. LAT1 expression yielded a statistically significant correlation with CD98 expression, cell proliferation, angiogenesis and glucose metabolism. In vitro experiments revealed that (18)F-FAMT was specifically transported by LAT1. CONCLUSIONS: The uptake of (18)F-FAMT within tumour cells is determined by the LAT1 expression and correlated with cell proliferation and angiogenesis in oesophageal cancer. The present experiments also confirmed the presence of LAT1 as an underlying mechanism of (18)F-FAMT accumulation.

ASC amino-acid transporter 2 (ASCT2) as a novel prognostic marker in non-small cell lung cancer.

BACKGROUND: ASC amino-acid transporter 2 (ASCT2) is a major glutamine transporter that has an essential role in tumour growth and progression. Although ASCT2 is highly expressed in various cancer cells, the clinicopathological significance of its expression in non-small cell lung cancer (NSCLC) remains unclear. METHODS: One hundred and four patients with surgically resected NSCLC were evaluated as one institutional cohort. Tumour sections were stained by immunohistochemistry (IHC) for ASCT2, Ki-67, phospho-mTOR (mammalian target of rapamycin), and CD34 to assess the microvessel density. Two hundred and four patients with NSCLC were also validated by IHC from an independent cohort. RESULTS: ASC amino-acid transporter 2 was expressed in 66% of patients, and was closely correlated with disease stage, lymphatic permeation, vascular invasion, CD98, cell proliferation, angiogenesis, and mTOR phosphorylation, particularly in patients with adenocarcinoma (AC). Moreover, two independent cohorts confirmed that ASCT2 was an independent marker for poor outcome in AC patients. CONCLUSIONS: ASC amino-acid transporter 2 expression has a crucial role in the metastasis of pulmonary AC, and is a potential molecular marker for predicting poor prognosis after surgery.

Prognostic significance of L-type amino-acid transporter 1 expression in surgically resected pancreatic cancer.

BACKGROUND: The expression of L-type amino-acid transporter 1 (LAT1) is tumour-specific and has been shown to have essential roles in cell growth and survival. However, little is known regarding the clinical significance of LAT1 expression in pancreatic cancer. This study was conducted to determine the prognostic significance of LAT1 expression. METHODS: A total of 97 consecutive patients with surgically resected pathological stage I-IV pancreatic ductal adenocarcinoma were retrospectively reviewed. Tumour sections were stained by immunohistochemistry for LAT1, CD98, Ki-67 and vascular endothelial growth factor (VEGF), and microvessel density was determined by CD34 and p53. RESULTS: L-type amino-acid transporter 1 and CD98 were highly expressed in 52.6% (51/97) and 56.7% (55/97) of cases, respectively (P=0.568). The expression of LAT1 within pancreatic cancer cells was significantly associated with disease stage, tumour size, Ki-67, VEGF, CD34, p53 and CD98. L-type amino-acid transporter 1 expression was confirmed to be a significant prognostic factor for predicting poor outcome by multivariate analysis. CONCLUSION: L-type amino-acid transporter 1 expression is a promising pathological marker for the prediction of outcome in patients with pancreatic cancer.

The role of the ADC value in the characterisation of renal carcinoma by diffusion-weighted MRI.

The purpose of this study is to evaluate the role of diffusion-weighted imaging (DWI) in combination with T(1) and T(2) weighted MRI for the characterisation of renal carcinoma. The institutional review board approved the study protocols and waived informed consent from all of the patients. 47 patients (32 male and 15 female; age range, 21-85 years; median age, 65 years) who had suspected renal lesions on abdominal CT underwent MRI for further evaluation and characterisation of the lesions from April 2005 to August 2007 in our university hospital. A region of interest was drawn around the tumour area on apparent diffusion coefficient (ADC) maps. Final diagnosis was confirmed by histological examination of surgical specimens from all patients. The ADC value was significantly higher in renal cell carcinoma (RCC) than in transitional cell carcinoma (2.71+/-2.35 x 10(-3) mm(2) s(-1) vs 1.61+/-0.80 x 10(-3) mm(2) s(-1); p = 0.022). While analysing the histological subtypes of RCC, a significant difference in ADC values between clear cell carcinoma and non-clear cell carcinoma was found (1.59+/-0.55 x 10(-3) mm(2) s(-1) vs 6.72+/-1.85 x 10(-3) mm(2) s(-1); p = 0.0004). Similarly, ADC values of RCC revealed a significant difference between positive and negative metastatic lesions (1.06+/-0.38 x 10(-3) mm(2) s(-1) vs 3.02+/-2.44 x 10(-3) mm(2) s(-1); p = 0.0004), whereas intensity on T(1) and T(2) weighted imaging did not reach statistical significance. In conclusion, DWI has clinical value in the characterisation of renal carcinomas and could be applied in clinical practice for their management.

Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I-III nonsmall cell lung cancer.

The clinical significance of L-type amino acid transporter 1 (LAT1) expression remains unclear, whereas many experimental studies have demonstrated that LAT1 is associated with the proliferation of cancer cells. The purpose of this study was to evaluate the prognostic value of LAT1 in patients with nonsmall cell lung cancer (NSCLC). A total of 321 consecutive patients with completely resected pathologic stage I-III NSCLC were retrospectively reviewed. Expression of LAT1 and proliferative activity, as determined by the Ki-67 labelling index, was also evaluated immunohistochemically and correlated with the prognosis of patients who underwent complete resection of the tumour. Expression of LAT1 was positive in 163 patients (51%) (29% of adenocaricnoma (58 of 200 patients), 91% of squamous cell carcinoma (91 of 100 patients), and 67% of large cell carcinoma (14 of 21 patients)). The 5-year survival rate of LAT1-positive patients (51.8%) was significantly worse than that of LAT1-negative patients (87.8%; P<0.001). L-type amino acid transporter 1 expression was significantly associated with lymph node metastasis and disease stage. Multivariate analysis confirmed that positive expression of LAT1 was an independent factor for predicting a poor prognosis. There was a significant correlation between LAT1 expression and Ki-67 labelling index. LAT1 expression is a promising pathological factor to predict the prognosis in patients with resectable stage I-III NSCLC.

Brain metabolic changes associated with predispotion to onset of major depressive disorder and adjustment disorder in cancer patients--a preliminary PET study.

OBJECTIVES: To explore neurobiological risk factors for major depressive disorder (MDD) and adjustment disorder in cancer patients by examining regional brain metabolism before psychiatric manifestation using positron emission tomography and by prospectively observing depressive and anxiety symptoms. METHOD: Cancer patients who showed no psychiatric symptoms when they underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) were followed up for one year using the Hospital Anxiety and Depression Scale (HADS). Fourteen patients who showed high HADS scores and 14 patients who showed low HADS scores were assessed by a psychiatrist 2 years after the PET scan and grouped into the deterioration group (n=10) and the no-change group (n=9). 18F-FDG PET images were analyzed to examine the difference in local brain glucose metabolism between the two groups. RESULTS: The deterioration group showed a decreased glucose metabolism in the right medial frontal gyrus (BA6) and an increased glucose metabolism in the right posterior cingulate (BA29), right anterior cingulate (BA25), left subcallosal gyrus (BA25), and left caudate compared with the no-change group. CONCLUSION: Cancer patients who later developed MDD or adjustment disorder showed regional brain metabolic changes. These regions may be associated with vulnerability to the onset of MDD or adjustment disorder in cancer patients.

HPA axis normalization, estimated by DEX/CRH test, but less alteration on cerebral glucose metabolism in depressed patients receiving ECT after medication treatment failures.

OBJECTIVE: To examine the clinical effects of electroconvulsive therapy (ECT) on depressed patients with medication treatment failures, we investigated the alterations in hypothalamic-pituitary-adrenocortical (HPA) function and regional cerebral metabolism rate of glucose (rCMRGlu) after ECT in these patients. METHOD: Before and after ECT, the combined dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test was administered to seven patients who were referred for ECT. In the same patients, (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) was also assessed. RESULTS: Cortisol response in the DEX/CRH test significantly decreased after a successful ECT. A significant hypometabolism in various frontal regions and hypermetabolism in the parietal regions of these patients when compared with controls remained after ECT. CONCLUSION: Depressed patients who failed trials of antidepressant medication showed a remission with ECT that was accompanied by resolution of HPA dysregulation. However, measures of cerebral brain metabolism did not resolve.

PET in the follow-up of differentiated thyroid cancer.

Fluorine-18-fluorodeoxyglucose (FDG) PET has become an increasingly important functional imaging modality in clinical oncology. This article will focus primarily on the role of FDG PET during treatment and follow-up of thyroid cancer. The major role of FDG PET is in patients with elevated thyroglobulin (Tg) levels where thyroid cancer tissue does not concentrate radioiodine rendering false-negative results on I-131 scanning. FDG PET imaging takes advantage of the increased uptake of FDG in cancer cells and is sensitive (60-94%) to the detection of recurrent or metastatic cancer in patients who have negative radioiodine scans. The specificity (25-90%) of PET imaging is relatively less than its sensitivity because some inflammatory processes avidly accumulate FDG. PET can fail to localize the tumour sites in some patients with well-differentiated thyroid cancer that retain good iodine ability. This can result the well recognized phenomenon of "flip-flop" depending on the differentiation of the thyroid cancer. Several studies have documented the higher accuracy of PET, compared with other imaging modalities in the evaluation of patients with recurrent or metastatic differentiated thyroid cancer. The value of thyroid stimulating hormone stimulation for FDG PET has recently been reported. Therefore, if available, this method should be considered in all patients of differentiated thyroid cancer with suspected recurrence and/or metastasis.

Gliomatosis cerebri evaluated by 18Falpha-methyl tyrosine positron-emission tomography.

Gliomatosis cerebri is a rare condition in which an infiltrative glial neoplasm spreads through the brain with preservation of the underlying structure. CT and MRI show diffuse abnormal density or signal, without mass effect, and because these findings are nonspecific, it is difficult to make a definitive diagnosis. Our purpose was to assess the usefulness of a new tumour-detecting amino acid tracer for positron-emission tomography (PET), L-[3-(18)F] alpha-methyl tyrosine (FMT), in patients with gliomatosis cerebri. We performed FMT PET, fluorodeoxyglucose FDG PET and MRI eight patients with gliomatosis cerebri and six with non-neoplastic disease, whose MRI also showed diffuse high signal on T2-weighted images. Standardised uptake (SUV) of FMT and FDG in the area of gliomatosis was obtained and the tumour-to-normal cortex (T/N) ratio of this was compared. The tumours were shown on FMT PET as areas of increased uptake, except in one patient with severe intracranial hypertension. There were significant differences between the SUV of FMT and the T/N ratio of FMT in patients and in controls (both P<0.01), and between the T/N ratio of FMT and FDG in patients ( P<0.01). Increased uptake of FMT PET strongly suggests neoplasia. FMT PET is valuable for differentiating gliomatosis cerebri from non-neoplastic diseases showing similar diffuse high signal on T2-weighted images and little contrast enhancement.

A comparative study of 11C-choline PET and [18F]fluorodeoxyglucose PET in the evaluation of lung cancer.

The purpose of this study was to compare the diagnostic value of 11C-choline positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) PET imaging in the detection of primary lung cancer and mediastinal lymph node metastases. Seventeen patients with histologically proven primary lung cancer were examined with both 11C-choline and FDG PET within a week of each study. Lung cancers were analysed visually and semiquantitatively using the ratio of tumour-to-normal radioactivity (T/N ratio) and standardized uptake value (SUV). Mediastinal lymph node metastases were analysed visually. Although both techniques delineated focal lesions with an increase in tracer accumulation in 13 patients, FDG PET identified three additional patients in whom 11C-choline PET did not visualize any lesion. In the detection of lung cancer <2 cm in size, FDG PET provided higher sensitivity (six of seven, 85.7%) than 11C-choline PET (four of seven, 57.1%). The T/N ratio and SUV were significantly higher with FDG PET (T/N ratio, 7.43+/-6.22; SUV, 4.05+/-3.05) than these were with 11C-choline PET (T/N ratio, 2.93+/-1.19; SUV, 2.93+/-0.79) (P<0.001). There was a significant positive correlation between the T/N ratios and SUVs of FDG and 11C-choline. In the assessment of mediastinal lymph node involvement, FDG PET detected lymph node metastases in two patients who were negative on 11C-choline PET, whereas both techniques could not detect tumour involvement in one patient. Both techniques have clinical value for the non-invasive detection of primary lung cancer that is 2 cm or greater in size. However, FDG PET is superior to 11C-choline PET in the detection of lung cancer that is less than 2 cm in diameter and in mediastinal lymph node metastases.

Assessment of myocardial viability with a positron coincidence gamma camera using fluorodeoxyglucose in comparison with dedicated PET.

The use of dual-head gamma camera modified positron coincidence detection (PCD) is a new, alternative method of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) imaging. This study investigated the potential ability of evaluating myocardial viability in patients with ischaemic heart disease by FDG imaging using PCD. A total of 21 patients (18 male, three female; mean age 59.7+/-8.5 years) with a history of previous myocardial infarction and confirmed coronary angiography underwent FDG PCD and FDG PET after oral glucose loading (75 g). Quantitative analysis was compared between images of FDG PCD and FDG PET. A significant linear correlation between the segmental percentage of FDG uptake obtained by PCD and PET was observed (r=0.63, P<0.001). By receiver operating characteristic (ROC) analysis, using FDG PET as the 'gold standard', at the 50% threshold value in PET, FDG PCD showed a sensitivity of 92% and specificity of 63% in detecting myocardial viability. Regional analysis showed lower agreement of FDG PCD and FDG PET in the inferior (79%) and septal (70%) walls compared with the other walls. Quantitative evaluation of myocardial viability using FDG PCD yielded comparable clinical results in apex, anterior and lateral walls to that of FDG PET. However, the agreement was lower in the inferior and septal walls. Therefore, results of FDG PCD should be carefully interpreted in evaluating myocardial viability in the inferior and septal walls. The application of a measured attenuation correction and scatter correction are needed to improve the detectability of myocardial viability in FDG imaging by coincidence gamma camera.

11C-choline PET for the detection of bone and soft tissue tumours in comparison with FDG PET.

We assessed and compared the usefulness of C-choline positron emission tomography (PET) with that of 2-[ F]fluoro-2-deoxy-D-glucose (FDG) PET for the differentiation between benign and malignant bone and soft tissue tumours. A total of 43 patients with 45 lesions were included. C-choline PET and FDG PET were performed from 5 and 40 min, respectively, after injection of 275-370 MBq tracer. PET data were evaluated by using the standardized uptake value (SUV) and were analysed according to the pathological data. C-choline uptake in malignancies was 4.9+/-2.1 (n=14), which was significantly higher than that in benign lesions (2.5+/-1.7, n=31) (P <0.0001). The sensitivity, specificity and accuracy of C-choline PET were 100%, 64.5% and 75.6%, respectively, when 2.59 of the SUV was used as the cut-off value. The FDG uptake in malignancies was 5.1+/-4.2 (n=14) and was also significantly larger than that in benign lesions 2.9+/-2.9 (n=31) (P<0.003). The sensitivity, specificity and accuracy of FDG PET were 85.7%, 41.9% and 55.6%, respectively (cut-off=1.83). The C-choline uptake in the lesions correlated with FDG uptake ( r=0.61, P<0.003). In receiver operating characteristic (ROC) analysis, the area under the ROC curve for C-choline PET (area=0.847) was higher than that for FDG PET (area=0.717). This study showed that C-choline PET was superior to FDG PET in differentiation between malignant and benign lesion in bone and soft tissue tumours. C-choline PET might be useful as a screening method for malignant bone and soft tissue tumours.

Oncological diagnosis using positron coincidence gamma camera with fluorodeoxyglucose in comparison with dedicated PET.

The purpose of this study was to compare the utility of a dual-head positron coincidence detection gamma camera (PCD) with that of dedicated positron emission tomography (PET) in the imaging of various malignancies using (18)F-fluorodeoxyglucose (FDG). 25 patients with known or suspected malignancies at various sites underwent imaging with both methods, and diagnostic performance on a lesion basis was compared. Tumour lesions were analyzed visually and semi-quantitatively using the ratio of tumour-to-background counts (T/B ratio). FDG PCD and FDG PET visually detected 34 (72.3%) lesions and 37 (78.7%) lesions, respectively. The mean T/B ratio and standard deviation (SD) of FDG PCD was 3.5+/-3.3, significantly lower than that of FDG PET (8.4+/-7.1, p<0.001). When tumour lesions were less than 2.0 cm in diameter, the sensitivity of FDG PCD was 37.5%, significantly inferior to that of FDG PET (50.0%, p<0.01). Sensitivity between FDG PCD and FDG PET in lesions of more than 2.0 cm diameter showed no statistically significant difference. This study indicates that FDG imaging with a dual-head coincidence detection gamma camera can provide suitable diagnostic performance for lesions greater than 2.0 cm diameter, but performed significantly worse than dedicated PET for lesions smaller than this.

Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging.

The purpose of this study was to assess the clinical potential of methyl-11C-choline (11C-choline) in the diagnosis of brain tumours. To this end, the results of 11C-choline positron emission tomography (PET) in 22 patients suspected of having brain tumours were compared with the findings of contrast-enhanced magnetic resonance (MR) imaging and fluorine-18 fluorodeoxyglucose PET. A histopathological diagnosis was made for each patient during open surgery. The standardised uptake values of brain tumours and the tumour-to-white matter count (T/W) ratios were determined. The degree of 11C-choline accumulation noted in PET images was compared with the gadolinium-enhanced areas of MR images. The mean T/W ratio of 11C-choline in high-grade gliomas was found to be higher than that in low-grade gliomas. This difference was statistically significant (mean+/-SD: 8.7+/-6.2, n=9 versus 1.5+/-0.7, n=5, P<0.03) when data pertaining to the prominent uptake of 11C-choline in a patient with a pilocytic astrocytoma were excluded. 11C-choline PET failed to detect non-neoplastic lesions in two patients. Areas of 11C-choline accumulation in PET scans were larger than areas enhanced on MR images in five cases involving high-grade gliomas. 11C-choline PET differentiated between low-grade gliomas and high-grade gliomas, but did not differentiate between low-grade gliomas and non-neoplastic lesions. The combination of 11C-choline PET and MR imaging may provide investigators with an accurate means by which to identify high-grade gliomas.

Alternating myocardial sympathetic neural function of athlete's heart in professional cycle racers examined with iodine-123-MIBG myocardial scintigraphy.

Myocardial sympathetic neural function in professional athletes who had the long-term tremendous cardiac load has not been fully investigated by myocardial iodine-123-metaiodobenzylguanidine (MIBG) uptake in comparison with power spectral analysis (PSA) in electrocardiography. Eleven male professional cycle racers and age-matched 11 male healthy volunteers were enrolled in this study. The low frequency components in the power spectral density (LF), the high frequency components in the power spectral density (HF), the LF/HF ratio and mean R-R interval were derived from PSA and time-domain analysis of heart rate variability in electrocardiography. The mean heart-to-mediastinum uptake ratio (H/M ratio) of the MIBG uptake, in professional cycle racers was significantly lower than that in healthy volunteers (p < 0.01) and HF power in professional cycle racers was significantly higher than that in healthy volunteers (p < 0.05). In the group of professional cycle racers, the H/M ratio showed a significant correlation with the R-R interval, as indices of parasympathetic nerve activity (r = 0.80, p < 0.01), but not with the LF/HF ratio as an index of sympathetic nerve activity. These results may indicate that parasympathetic nerve activity has an effect on MIBG uptake in a cyclist's heart.

Effect of a cyclooxygenase-2 inhibitor, FK3311, in a canine lung transplantation model.

BACKGROUND: In the process of ischemia-reperfusion, inflammatory cytokines and arachidonic acid metabolites are released and followed by tissue damage. FK3311 (FK) is a selective cyclooxygenase-2 inhibitor that inhibits conversion of arachidonic acid into thromboxane A2 or prostaglandin I2. We investigated the effects of FK in canine lung transplantation. METHODS: FK3311 was administered in the FK group, and vehicle was injected in the control group. The left lung was orthotopically transplanted after 12-hour preservation in Euro-Collins solution. After reperfusion, the right pulmonary artery and bronchus were ligated, and the animals were observed. Pulmonary gas exchange and hemodynamics were measured, histopathologic damages were investigated, and technetium-99m-labeled albumin scintigraphy was performed. The serum prostanoid levels were also measured. RESULTS: In the FK group, pulmonary gas exchange and hemodynamics were significantly (p < 0.05) better, histologic damage and neutrophil infiltration was reduced, and technetium-99m-albumin accumulation was considerably suppressed. Also, thromboxane B2 was significantly (p < 0.05) lower, but 6-keto-prostaglandin F1alpha was not significantly reduced. CONCLUSIONS: FK3311 generates protective effects on lung transplantation by a marked inhibition of thromboxane A2.

A basic study on lesion detectability for hot spot imaging of positron emitters with dedicated PET and positron coincidence gamma camera.

The aim of this study was to explore the correlations of detectability and the semi-quantification for hot spot imaging with positron emitters in positron emission tomography (PET) and with a positron coincidence detection system (PCD). Phantom study results for the measurement of the lesion-to-background (L/B) ratio ranged from 2.0 to 30.3, and detectability for hot spot lesion of PET and PCD were performed to correspond to clinical conditions. The detectability and semi-quantitative evaluation of hot spots from 4.4 mm to 36.9 mm in diameter were performed from the PET and PCD images. There were strong correlations between the L/B ratios derived from PET and PCD hot spot images and actual L/B ratios; but the L/B ratio derived from PET was higher than that from PCD with a significant difference of 10% to 54.8%. The detectability of hot spot imaging of PCD was lower than that of PET at 64.8% (PCD) versus 77.8% (PET). Even the actual L/B ratio was 8.0, hot spots more than 10.6 mm in diameter could be clearly identified with PCD imaging. The same identification could be achieved with PET imaging even when the actual L/B ratio was 4.0. This detailed investigation indicated that FDG PCD yielded results comparable to FDG PET on visual analysis and semi-quantitative analysis in detecting hot spots in phantoms, but semi-quantitative analysis of the L/B ratio with FDG PCD was inferior to that with FDG PET and the detectability of PCD in smaller hot spots was significantly poor.