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.

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.

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.

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.

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.

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.

Isolated limb perfusion in the sarcoma-bearing rat: a novel preclinical gene delivery system.

Reliable site-specific delivery of genetic constructs remains a challenging component of gene-based therapy of solid tumors. Isolated limb perfusion (ILP) continues to be evaluated for treatment of locally advanced soft tissue sarcomas because this approach uniquely directs therapeutic agents into the tumor-bearing extremity without significant systemic leak. In light of these considerations, we tested the hypothesis that ILP could be used to deliver genes carried in viral vectors to the sarcoma-bearing rat extremity, resulting in demonstrable gene transfer into the tumor. ILP was performed in rats by cannulating the femoral artery and vein, isolating the hind limb from systemic circulation by tourniquet, and cycling perfusate for 15 min at a rate of 2.4 ml/min. Leakage into the systemic circulation was 7.5% of the total perfusate concentrated in the isolated limb, as determined by perfusion with technetium 99m-tagged RBCs. We used the ILP technique to perfuse rat hind limbs bearing syngeneic fibrosarcoma tumor nodules with the replication-defective adenovirus Ad5LacZ, which expresses the bacterial beta-galactosidase. 5-Bromo-4-chloro-3-indolyl-beta-D-galactoside staining of the perfused limb tissues confirmed gene transfer to the tumor and peritumoral tissue, demonstrating that the tumor was part of the perfusion circuit and that gene therapy delivered via this method was feasible. These results suggest that adaptation of this preclinical gene delivery model to administer genetic constructs aimed at controlling tumor growth may prove beneficial to patients with extremity sarcomas.

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.

Presurgical diagnosis of a primary carcinoid tumor of the thymus with MIBG.

A primary carcinoid tumor of the thymus showing ectopic ACTH syndrome was evaluated scintigraphically with four radiopharmaceuticals and a fluorescence method. Iodine-123-MIBG and 201Tl-Cl scintigraphy clearly demonstrated the tumor. Gallium-67-citrate and 99mTc(V)-DMSA showed no tumor uptake. The fluorescence method confirmed numerous storage granules of norepinephrine. Iodine-123-MIBG scintigraphy could be useful in the presurgical diagnosis of carcinoid tumors of the thymus.

Grade II astrocytoma visualized by technetium-99m-ECD SPECT.

We present a case of primary brain tumor demonstrating increased uptake of 99mTc-ECD. Astrocytoma (Grade II) showed significantly increased cerebral blood perfusion on dynamic images and homogeneously increased uptake on static images with 99mTc-ECD brain SPECT. There seems to be some difference in perfusion and mechanism of tumor uptake among the cerebral blood flow imaging agents (99mTc-ECD, 99mTc-HMPAO and [123I]-IMP) and 201TI-chloride.

Direct labeling of macroaggregated albumin with indium-111-chloride using acetate buffer.

UNLABELLED: Indium-111-labeled macroaggregated albumin (MAA) would be suitable for combined pulmonary perfusion and ventilation scan using a 99mTc ventilation agent. METHODS: MAA suspended in 0.1 M sodium acetate buffer, pH 5.8, was incubated with 111In-chloride for 30 min at room temperature. An in vitro study of the obtained 111In-MAA was performed for labeling efficiency and stability in human normal serum. The 111In-MAA was intravenously injected into normal mice, and the biodistribution was studied at 15 and 180 min postinjection. A gamma camera image was obtained at 15 min after injection. RESULTS: MAA was directly and stably labeled with 111In-chloride, and the labeling efficiency of the preparation was more than 96%. More than 90% of the administered 111In-MAA was caught in the murine lung. The scintigraphy with 111In-MAA showed a clearly visualized murine lung. CONCLUSION: Indium-111-MAA can be conveniently prepared by direct labeling at room temperature. It provides an alternative perfusion tracer for combined perfusion-ventilation imaging.

Immunoscintigraphy of aortic dissection with 99mTc-labeled murine anti-smooth muscle myosin monoclonal antibody in rats.

UNLABELLED: Aortic dissection is among the most common of fatal conditions of the aorta. Prompt and accurate diagnosis of the site and extent of the lesion is necessary for adequate therapy. However, this catastrophic disease, characterized by extensive damage to smooth muscle cells, lacks specific signs and symptoms. As a result, the diagnosis is still frequently missed today and a new diagnostic method to specifically identify aortic dissection would be attractive. The purpose of this study was to examine the feasibility of radioimmunoscintigraphy using 99mTc-anti-smooth muscle myosin monoclonal antibody (SM-MAb) for the noninvasive diagnosis of aortic dissection in the rat experimental model. METHODS: The accumulation of 99mTc-anti-SM-MAb was studied, and scintigraphic imaging with 99mTc-anti-SMMAb was performed in rats immediately after experimental aortic dissection and 1 and 2 wk later. RESULTS: The radioactivity of 99mTc-anti-SM-MAb in the dissected aorta showed a significant increase compared both with the normal portion of the aorta and with blood 6 h after injection of the radiotracer; the ratio of the percentage injected dose per gram (%lD/g) in the lesion to that retained in the normal portion was 4.17 +/- 1.47. Scintigraphic imaging with 99mTc-anti-SM-MAb allowed distinct visualization of the dissected aorta with specific accumulation of antibody 6 h after tracer injection. Selective accumulation of the tracer in the dissected portion of the aorta persisted even 1 wk after aortic injury, allowing clear visualization of the dissected lesion by scintigraphy. CONCLUSION: Radioimmunoscintigraphy using anti-SM-MAb is a potentially useful noninvasive diagnostic method for imaging aortic dissection.

Semiquantitative SPECT tumor uptake of technetium-99m-labeled anti-CEA monoclonal antibody in colorectal tumor.

UNLABELLED: Technetium-99m-BW431/26 images were compared to images of resected tumor specimens to evaluate the efficacy and accuracy of SPECT imaging of colorectal carcinoma. METHODS: Immunoscintigraphy with 99mTc-BW431/26 was performed on seven patients with colorectal carcinoma and one patient with a benign colorectal tumor. Accumulation of 99mTc-BW431/26 in the tumor was expressed as the tumor-to-normal tissue count ratio (SPECT T/N ratio) calculated by a region of interest method on the SPECT images obtained 24 hr after administration of 99mTc-BW431/26. All patients underwent research of the tumor immediately after 24-hr imaging, and the radioactivity in tumor specimen and normal tissue was measured to calculate the tissue T/N ratio. RESULTS: SPECT demonstrated definite increased tracer uptake by the tumor in all colorectal cancer patients. The benign lesion showed tracer uptake to a lesser extent. SPECT, however, failed to visualize a 10-mm lesion in a patient with familial adenomatous polyposis despite a tissue T/N ratio of 4.8, while autoradiography showed radioactivity uptake in the polyps. CONCLUSION: Although SPECT has limitations in detecting small lesions because of its limited spatial resolution, T/N ratios could be measured exactly by SPECT if the lesion is of a certain volume. SPECT imaging with 99mTc-BW431/26 can precisely evaluate tracer uptake in tumors and predict the efficacy of radioimmunotherapy in patients with colorectal cancer.

Effect of inhaled furosemide on lung clearance of technetium-99m-DTPA.

UNLABELLED: The diuretic furosemide has been reported to have a protective effect on allergic asthmatic reactions. This study was performed to investigate the effect of aerosolized furosemide on the lung clearance of 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA). METHODS: Pulmonary clearance rates of 99mTc-DTPA were measured by a computerized gamma camera with and without the inhalation of aerosol furosemide in 6 nonsmoking normal volunteers (Group 1), 7 smokers without pulmonary disease (Group 2) and 11 patients with asthma (Group 3). RESULTS: None of the six normal volunteers showed significant effects of inhaled furosemide on the 99mTc-DTPA clearance rates. Three of seven smokers presented an accelerated 99mTc-DTPA clearance by inhaled furosemide and the other four showed no significant change of 99mTc-DTPA clearance by furosemide inhalation. However, in 10 of 11 patients with asthma, there was significant suppression of 99mTc-DTPA clearance by furosemide inhalation. CONCLUSION: Asthmatics possess a furosemide-sensitive mechanism. Pulmonary aerosol scintigraphy with 99mTc-DTPA will be useful in predicting the effect of inhaled furosemide therapy.

Clinical evaluation of thallium-201 SPECT in supratentorial gliomas: relationship to histologic grade, prognosis and proliferative activities.

We performed 201Tl SPECT and cell kinetic studies on 28 presurgical patients with supratentorial gliomas by administering bromodeoxyuridine (BUdR). All patients had surgery and had follow-up for more than 25 mo. In patients with grade IV glioma (198.1% +/- 32.8%, n = 10), the 201Tl index, expressed as the count rate of the tumor site to the count rate over the contralateral normal region, was significantly higher than that in patients with grade III glioma (140.5% +/- 15.1%, n = 4, p < 0.01) or low-grade glioma (104.1% +/- 22.6%, n = 14, p < 0.001). A significant correlation was observed between the 201Tl index and BUdR-positive cells in excised tumor specimens (r = 0.67, p < 0.001). The 201Tl index of the 12 patients who died was higher than those who survived (173.2% versus 122.4%, p < 0.01). These results show the clinical utility of 201Tl brain SPECT in imaging supratentorial glioma and that the 201Tl index is representative of proliferative activity of the tumor.

CaNa2EDTA for improvement of radioimmunodetection and radioimmunotherapy with 111In and 90Y-DTPA-anti-CEA MAbs in nude mice bearing human colorectal cancer.

UNLABELLED: 111In and 90Y, dissociated from 111In-labeled-monoclonal antibody (MAb) and 90Y-labeled MAb, may cause deterioration of the image quality in radioimmunodetection (RID) and undesirable irradiation of nontargeted tissue in radioimmunotherapy (RIT), respectively. The aim of this study was to investigate any improvement in RID and RIT with 111In-MAb and 90Y-MAb by pre- and postadministration of calcium disodium ethylenetriaminetetraacetic acid (CaNa2EDTA). METHODS: Murine MAb F33-104 against carcinoembryonic antigen (CEA) was labeled with 111In or 90Y by the diethylenetriamine pentaacetic (DTPA)-anhydride method. The influence of CaNa2EDTA on loss of radioactivity from 111In-MAb or 90Y-MAb in serum was investigated in vitro. The effects of CaNa2EDTA, administered before and after 111In-MAb or 90Y-MAb, on the biodistribution of radioactive isotopes in nude mice bearing human colon adenocarcinoma LS 180 tumor expressing CEA, or human pulmonary carcinoma PC 9 tumor expressing no CEA, were then examined. As a control, 0.9% NaCl was used in both the in vitro and in vivo studies. RESULTS: CaNa2EDTA did not cause any decrease in levels of radioactivity of radiolabeled MAbs. Pre- and post-treatment with CaNa2EDTA reduced radioctivity in both specific and nonspecific tumors at 72 h after 111In-MAb injection resulting in an increase of the specific tumor-to-nonspecific tumor radioactivity ratio. The levels of hepatic and renal radioactivity were also subsequently decreased by CaNa2EDTA. On the other hand, CaNa2EDTA pre- and post-treatment reduced levels of bony, hepatic, and renal radioactivity at 24, 72, and 72 h, respectively, after 90Y-MAb injection, although it had no effect on tumor radioactivity. CONCLUSION: Pre- and post-treatment with CaNa2EDTA would be of great use in humans who undergo RID or RIT with 111In-MAb and 90Y-MAb accompanied by disassociation of the labeled radionuclides.

18F alpha-methyl tyrosine PET studies in patients with brain tumors.

UNLABELLED: We have developed 18F-labeled alpha-methyl tyrosine (FMT) for PET imaging. The aim of this study was to evaluate the clinical application potential of FMT for patients with brain tumors. METHODS: Eleven healthy volunteers and 20 patients with brain tumors were injected with 185 MBq (5 mCi) FMT. In 3 healthy volunteers, whole-body imaging and urinary and plasma analysis were conducted for the assessment of the biodistribution of FMT. The normal range of cortical standardized uptake value (SUV) as a reference for comparing tumor SUV of FMT was estimated by using PET data obtained at 30 min postinjection in 8 healthy volunteers. Dynamic PET scans were conducted for 100 min in 4 healthy volunteers and for 30 min in 15 patients with brain tumors. The 10-min static images in another 4 volunteers and all patients were obtained at 30 min postinjection. In 13 patients, FMT uptake in the brain tumor was compared with 18F-fluorodeoxyglucose (FDG). Tumor-to-normal cortex count (T/N) ratio and tumor-to-white matter count (T/W) ratio and SUVs of brain tumors were determined on FMT and FDG PET images. RESULTS: Approximately 1480 MBq (40 mCi) FMT were produced in one radiosynthesis. Percentage injected dose (%ID) of FMT in the brain ranged from 2.8% to 4.9%, and approximately 50%ID of FMT was excreted in urine during 60 min postinjection, of which 86.6% was unmetabolized FMT. A faint physiological brain uptake with SUV of 1.61 +/- 0.32 (mean +/- SD, n = 8) was observed in healthy volunteers. Tumor SUV of FMT ranged from 1.2 to 8.2, with mean value of 2.83 +/- 1.57 (n = 23), which was significantly higher than that of the cortical area in healthy volunteers (P < 0.01). T/N and T/W ratios of FMT were significantly higher than those of FDG (2.53 +/- 1.31 versus 1.32 +/- 1.46, P < 0.001; 3.99 +/- 2.10 versus 1.39 +/- 0.65, P < 0.0001, respectively). CONCLUSION: FMT, like other radiolabeled amino acids, can provide high-contrast PET images of brain tumors.

Independent thallium-201 accumulation and fluorine-18-fluorodeoxyglucose metabolism in glioma.

UNLABELLED: SPECT with 201TI is an effective procedure for evaluating the malignancy of glioma. Our goal was to investigate the diagnostic relevance of both 201TI SPECT and [18F]fluorodeoxyglucose (FDG) PET and the relation between 201TI uptake and glucose metabolism in glioma using comparative SPECT and PET studies. METHODS: Thallium-201 SPECT and FDG dynamic PET studies were performed in 20 patients with untreated glioma (5 with glioblastoma, 5 with anaplastic glioma, 10 with low-grade glioma). Thallium-201 uptake in the tumor was estimated using the 201TI index, defined as the ratio of 201TI uptake in the tumor to that in the contralateral normal brain on SPECT images obtained 15 min after intravenous injection. We measured regional glucose metabolic parameters, including rate constants and regional cerebral metabolic rate of glucose utilization (rCMRgl), in the tumor. We then compared the regional 201TI index and glucose metabolic parameters with the histologic characteristics, malignancy and computed tomographic/ magnetic resonance imaging findings. In addition, we investigated the correlation between the 201TI index and glucose metabolic parameters. RESULTS: Thallium-201 SPECT showed abnormal 201TI uptake in all patients with glioblastoma and anaplastic glioma. Thallium-201 indices of glioblastoma (202.6 +/- 22.1%) and anaplastic glioma (176.6% +/- 26.6%) were significantly higher than that for low-grade glioma (106.7% +/- 13.8%). The rCMRgl value of glioblastoma (17.6 +/- 3.5 mumole/100 g/min) was also significantly higher than that for low-grade glioma (10.8 +/- 4.5 mumole/100 g/min), although rCMRgl showed a large variability in both high- and low-grade glioma. Rate constants of FDG kinetics had no correlation with histological grade of glioma. Some patients with high-grade glioma, however, showed false-negative results with FDG-PET because of high normal brain uptake of FDG. Conversely, most low-grade glioma could not be localized by 201TI SPECT. There was no correlation between the 201TI index and glucose metabolic parameters. CONCLUSION: Thallium-201 indices and rCMRgl values for glioblastoma were higher than those for low-grade glioma. Thallium-201 uptake in the tumor may be independent of increased glucose transport or metabolism. Thallium-201 SPECT and FDG-PET are complementary in the diagnosis of glioma, although 201TI SPECT is more significantly correlated with the malignancy of glioma.

FR167653 ameliorates pulmonary damage in ischemia-reperfusion injury in a canine lung transplantation model.

BACKGROUND: Interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha) are recognized as important factors in ischemia-reperfusion (I/R) injury. FR167653 has been characterized as a potent suppressant of IL-1 and TNF-alpha production. We previously reported that FR167653 suppressed the expression of IL-1 beta mRNA after reperfusion and ameliorated pulmonary I/R injury following 3-hour left lung warm ischemia in dogs. The aim of this study was to investigate the effects of FR167653 on I/R injury in a canine left, single, lung transplantation model. METHODS: We used 10 pairs of weight-matched dogs. We assigned 5 pairs to the FR group, in which each animal received FR167653 (1 mg/kg/hr) IV from 30 minutes before ischemia until 2 hours after reperfusion; we treated the transplanted lungs with FR167653 after the onset of reperfusion. The others were assigned to the control group. After 8-hour preservation with 4 degrees C Euro-Collins solution, orthotopic left, single, lung transplantation was performed. During a 5-minute clamping test at the right pulmonary artery of each recipient, the left (transplanted) pulmonary arterial pressure (L-PAP), left (transplanted) pulmonary vascular resistance (L-PVR), arterial oxygen pressure (PaO(2)), and alveolar-arterial oxygen pressure difference (A-aDO(2)) were measured. We harvested transplanted lung specimens for histologic study, and we counted polymorphonuclear neutrophils (PMNs), which were identified by staining with naphthol AS-D cholroacetate esterase. Pulmonary perfusion and ventilation scintigraphy (Tc-99m-MAA and Xe-133) were performed. We observed the animals for 3 days after transplantation. RESULTS: The PAP, L-PVR, PaO(2), and A-aDO(2) revealed significantly (p < 0.05) better function in the FR group than in the control group. Histologically, lung edema was milder, and PMN infiltration was significantly (p < 0.05) lower in the FR group than in the control group. Xe-133 and Tc-99m-MAA were widely distributed throughout the graft lung in the FR group. Three-day survival rates in FR and control groups were 60% and 20%, respectively. CONCLUSIONS: FR167653 appears to generate a protective effect on I/R injury in lung transplantation in dogs.

The effect of FK409-a nitric oxide donor-on canine lung transplantation.

BACKGROUND: Nitric oxide (NO) is known to have beneficial effects in ischemia-reperfusion (I/R) injury through maintaining endothelial integrity, inhibiting leukocyte adhesion and platelet aggregation, and inducing vasodilation. The effect of FK409 (FK), a spontaneous NO donor, was investigated in a canine lung transplantation model. METHODS: Ten pairs of weight-matched dogs were used. Five pairs were assigned to the FK group, to which FK (5 microg/kg/min) was administered intravenously from 30 minutes prior to ischemia until the induction of ischemia in the donor, and from 15 minutes prior to reperfusion until 45 minutes after reperfusion in the recipient. The others were assigned to the control group. After 8-hour preservation in 4 degrees C Euro-Collins solution, orthotopic single-lung transplantation was performed. During a 5-minute clamping test of the right pulmonary artery, left pulmonary arterial pressure (L-PAP), left pulmonary vascular resistance (L-PVR), arterial oxygen pressure (PaO(2)), and alveolar-arterial oxygen pressure difference (A-aDO(2)) were measured. The lung specimens were harvested for histologic study, and polymorphonuclear neutrophils (PMNs) were counted. Pulmonary perfusion and ventilation scintigraphy (Tc-99m-MAA and Xe-133) were performed. RESULTS: PAP, L-PVR, PaO(2), and A-aDO(2) revealed significantly (p < 0.05) better function in the FK group than in the control group. Histologically, edema was more mild, and PMN infiltration was significantly (p < 0.05) lower in the FK group than in the control group. Xe-133 and Tc-99m-MAA were widely distributed throughout the graft lung in the FK group. The 2-day survival rate was 100% in the FK group, which was significantly (p < 0.05) better than the rate (40%) in the control group. CONCLUSIONS: FK appears to generate a protective effect on I/R injury in lung transplantation.