Publications (19)76.19 Total impact
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Article: (4S)-4-(3-18F-Fluoropropyl)-L-Glutamate for Imaging of xC Transporter Activity in Hepatocellular Carcinoma Using PET: Preclinical and Exploratory Clinical Studies.
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ABSTRACT: (4S)-4-(3-(18)F-fluoropropyl)-l-glutamate ((18)F-FSPG, or BAY 94-9392) is a new tracer to assess system x(C)(¯) transporter activity with PET. The aim of this study was to explore the tumor detection rate of (18)F-FSPG, compared with that of (18)F-FDG, in patients with hepatocellular carcinoma (HCC). METHODS: Preclinically, in vivo HCC models of orthotopically implanted Huh7 and MH3924a cancer cells were studied with (18)F-FSPG in Naval Medical Research Institute nude mice (n = 3) and August-Copenhagen Irish rats (n = 4), respectively. Clinically, 5 patients with HCC who had hyper- or isometabolic lesions on (18)F-FDG PET were enrolled for evaluation of the tracer. Dynamic whole-body PET images with (18)F-FSPG were acquired for up to 120 min after injection of approximately 300 MBq of (18)F-FSPG. Immunohistochemical expression levels of the xCT subunit of the system x(C)(¯) and CD44 of HCC were studied in 4 patients with HCC. RESULTS: Strong tumor uptake and low background from nontarget tissue allowed excellent tumor visualization in animal models with orthotopically implanted liver tumors. (18)F-FSPG PET procedures were well tolerated in all patients. (18)F-FSPG PET and (18)F-FDG detected lesions in 5 of 5 and 3 of 5 patients, respectively. The maximal standardized uptake values (SUV) were comparable ((18)F-FSPG, 4.7 ± 3.2; (18)F-FDG, 6.1 ± 2.9). The ratios of maximal SUV of the tumor to mean SUV of normal liver were also comparable ((18)F-FSPG, 3.6 ± 2.2; (18)F-FDG, 2.7 ± 1.3), but the mean SUV of normal liver of (18)F-FSPG was significantly lower than that of (18)F-FDG (P < 0.05). Two patients with HCC who showed both xCT and CD44 expression had moderate or intense accumulation of (18)F-FSPG, but the remaining 2 patients with negative CD44 expression showed mild uptake. CONCLUSION: (18)F-FSPG was successfully translated from preclinical evaluation into patients with HCC. (18)F-FSPG may be a promising tumor PET agent with a high cancer detection rate in patients with HCC.Journal of Nuclear Medicine 12/2012; · 6.38 Impact Factor -
Article: Carnitine sensitizes TRAIL-resistant cancer cells to TRAIL-induced apoptotic cell death through the up-regulation of Bax.
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ABSTRACT: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family with apoptosis-inducing activity. Given that TRAIL selectively induces cell death in various tumors but has little or no toxicity to normal cells, TRAIL agonists have been considered as promising anti-cancer therapeutic agents. However, the resistance of many primary tumors and cancer cells to TRAIL poses a challenge. In our present study, we found that carnitine, a metabolite that transfers long-chain fatty acids into mitochondria for beta-oxidation and modulates protein kinase C activity, sensitizes TRAIL-resistant cancer cells to TRAIL. Combination of carnitine and TRAIL was found to synergistically induce apoptotic cell death through caspase activation, which was blocked by a pan caspase inhibitor, but not by an inhibitor of autophagy or an inhibitor of necrosis. The combination of carnitine and TRAIL reversed the resistance to TRAIL in lung cancer cells, colon carcinoma cells, and breast carcinoma cells. We further demonstrate that carnitine, either alone or in combination with TRAIL, enhances the expression of the pro-apoptotic Bcl-2 family protein, Bcl-2-associated X protein (Bax). The down-regulation of Bax expression by small interfering RNA reduced caspase activation when cells were treated with TRAIL, and experiments with cells from Bax-mice confirmed this result. Taken together, our current results suggest that carnitine can reverse the resistance of cancer cells to TRAIL by up-regulating Bax expression. Thus, a combined delivery of carnitine and TRAIL may represent a new therapeutic strategy to treat TRAIL-resistant cancer cells.Biochemical and Biophysical Research Communications 10/2012; · 2.48 Impact Factor -
Article: A pilot study for the early assessment of the effects of BMS-754807 plus gefitinib in an H292 tumor model by [(18)F]fluorothymidine-positron emission tomography.
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ABSTRACT: BMS-754807 is an inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor that also represses aurora kinase. Cancers that express high levels of IGF-1/IGF-1R are sensitive to BMS-754807; however, it shows limited efficacy in non-small cell lung cancer (NSCLC) in which IGF-1R-driven signals may not be dominant factors in cell proliferation. In this study, we investigated whether a combination of BMS-754807 and gefitinib would be synergistic in H292 NSCLC and whether [(18)F]fluorothymidine ([(18)F]FLT)-positron emission tomography (PET) could predict the effects. We found that BMS-754807 synergized with gefitinib in reducing cell viability (combination index = 0.38) and Akt phosphorylation, and increasing the subG(1) fraction in H292 cells. BMS-754807 alone and in combination with gefitinib increased the cells in G(2)M phase and polyploid cells and decreased the phosphorylation of IGF-1R and histone H3. The inhibition of tumor growth by gefitinib was increased by BMS-754807 (%T/C, 17.5 % vs. 58.0 % for gefitinib alone and combined treatment, respectively), although BMS-754807 alone had little effect. The standardized uptake value by [(18)F]FLT-PET were increased in vehicle-treated mice by 73 %, minimally changed in gefitinib- or BMS-754807-treated mice, whereas decreased in co-treated mice by -48.8 % between day 0 and day 3. The combination therapy with BMS-754807 and gefitinib might be a more effective anticancer strategy than BMS-754807 alone in tumors that are less IGF-1R-dependent and that [(18)F]FLT-PET can be used to assess early therapeutic responses.Investigational New Drugs 09/2012; · 3.36 Impact Factor -
Article: Use of drug-eluting stent with provisional T-stenting technique in the treatment of renal artery bifurcation stenosis; long-term angiographic follow-up.
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ABSTRACT: Atherosclerotic renal artery stenosis (RAS) usually involves the ostium and the proximal one-third of the renal artery main branch. Percutaneous renal artery angioplasty with stent placement is a well recognized treatment for atherosclerotic RAS. Occasionally, atherosclerotic RAS involves renal artery bifurcations. However, stent implantation in atherosclerotic RAS involving bifurcation is not only troublesome, but also challenging because of side branch occlusion and in-stent restenosis (ISR). In the present report, we describe the use of drug-eluting stents (DES) with provisional T-stenting technique for the treatment of renal artery bifurcation lesion. Follow-up angiogram showed no significant ISR 18 months after the procedure. In the treatment of renal bifurcation lesions, a two-stent strategy using DES could be a viable option in selected patients.Journal of Korean medical science 11/2011; 26(11):1512-4. · 0.84 Impact Factor -
Article: p34 (SEI-1) inhibits ROS-induced cell death through suppression of ASK1.
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ABSTRACT: Apoptosis signal-regulating kinase 1 (ASK1) is a key factor for controlling several cellular events including the cell cycle, senescence and apoptosis, in response to reactive oxygen species (ROS). However, the mechanisms that regulate ASK1 protein levels remain largely unexplored. In this study, we demonstrate that p34 (SEI-1) , a positive cell cycle regulator with an oncogenic potential, inhibits ROS-induced cell death by suppressing ASK1. We first found that p34 (SEI-1) -expressing cells have enhanced resistance to hydrogen peroxide (H 2O 2). Moreover, ectopic expression of p34 (SEI-1) clearly inhibited H 2O 2-induced phosphorylation of ASK1 in the colon cancer cell lines- HCT116 and SW620-in association with a decrease in ASK1 protein levels. Interestingly, p34 (SEI-1) induced ubiquitination of ASK1, however, no direct interaction was found between p34 (SEI-1) and ASK1. These results suggest that p34 (SEI-1) inhibits ROS-induced cell death through by indirectly inducing ubiquitination of ASK1.Cancer biology & therapy 09/2011; 12(5):421-6. · 2.64 Impact Factor -
Article: Transcatheter arterial embolization as treatment for a life-threatening retroperitoneal hemorrhage complicating heparin therapy.
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ABSTRACT: Spontaneous retroperitoneal hemorrhage is a distinct clinical entity that can present in the absence of specific underlying pathology or trauma and is typically associated with anticoagulation therapy. We report a case of a 74-year-old female patient with a cerebral infarction related to atrial fibrillation who developed a spontaneous lumbar arterial hemorrhage complicating heparin therapy. The diagnosis was suggested by a computed tomography scan and confirmed by angiography. She was treated successfully with transcatheter embolization.The Korean Journal of Internal Medicine 09/2011; 26(3):352-5. -
Article: Randomized comparison of everolimus-eluting stent versus sirolimus-eluting stent implantation for de novo coronary artery disease in patients with diabetes mellitus (ESSENCE-DIABETES): results from the ESSENCE-DIABETES trial.
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ABSTRACT: Drug-eluting stents significantly improved angiographic and clinical outcomes compared with bare metal stents in diabetic patients. However, a comparison of everolimus-eluting stents and sirolimus-eluting stents in diabetic patients has not been evaluated. Therefore we compared effectiveness of everolimus-eluting stents and sirolimus-eluting stents in patients with diabetes mellitus. This prospective, multicenter, randomized study compared everolimus-eluting stent (n=149) and sirolimus-eluting stent (n=151) implantation in diabetic patients. The primary end point was noninferiority of angiographic in-segment late loss at 8 months. Clinical events were also monitored for at least 12 months. Everolimus-eluting stents were noninferior to sirolimus-eluting stents for 8-month in-segment late loss (0.23 ± 0.27 versus 0.37 ± 0.52 mm; difference, -0.13 mm; 95% confidence interval, -0.25 to -0.02; upper 1-sided 95% confidence interval, -0.04; P<0.001 for noninferiority), with reductions in in-stent restenosis (0% versus 4.7%; P=0.029) and in-segment restenosis (0.9% versus 6.5%; P=0.035). However, in-stent late loss (0.11 ± 0.26 versus 0.20 ± 0.49 mm; P=0.114) was not statistically different between the 2 groups. At 12 months, ischemia-driven target lesion revascularization (0.7% versus 2.6%; P=0.317), death (1.3% versus 3.3%; P=0.448), and myocardial infarction (0% versus 1.3%; P=0.498) were not statistically different between the 2 groups. Major adverse cardiac events, including death, myocardial infarction, and ischemia-driven target lesion revascularization (2.0% versus 5.3%; P=0.218), were also not statistically different between the 2 groups. Everolimus-eluting stents were noninferior to sirolimus-eluting stents in reducing in-segment late loss and reduced angiographic restenosis at 8 months in patients with diabetes mellitus and coronary artery disease.Circulation 08/2011; 124(8):886-92. · 14.74 Impact Factor -
Article: Long QT syndrome and torsade de pointes associated with Takotsubo cardiomyopathy.
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ABSTRACT: Prolongation of QTc interval associated with Takotsubo cardiomyopathy (TC) has previously been reported in published case series. We report an unusual case of a patient who presented with TC associated with long-QT syndrome and developed cardiac arrest secondary to torsade de pointes. Since QT prolongation and bradycardia persisted after the resolution of TC, the patient received permanent pacemaker. Since then additional event did not occur. QT prolongation and bradycardia could be persistent even after recovery of TC, and permanent pacemaker insertion may be a treatment option of long QT syndrome related with TC.Journal of Korean medical science 07/2011; 26(7):959-61. · 0.84 Impact Factor -
Article: Quantitative analysis of thymidine kinase 1 and 5'(3')-deoxyribonucleotidase mRNA expression: the role of fluorothymidine uptake.
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ABSTRACT: Thymidine kinase 1 (TK1) and 5'(3')-deoxyribonucleotidase (dNT1) regulate the metabolism of thymidine and its analogs. However, the expression patterns and roles of these enzymes in fluorothymidine (FLT) uptake have not been systemically studied. TK1 and dNT1 mRNAs were determined by quantitative PCR in 20 asynchronously growing lung and colon cancer cell lines. [3H]FLT uptake and doubling time were measured. The TK1/GAPDH values varied from 3.09×10(-3)±6.62×10(-4) to 2.44×10(-2)±8.49×10(-4) and dNT1/GAPDH values from 5.84×10(-4)±4.88×10(-5) to 1.59×10(-2)±1.20×10(-3). The correlation coefficient of TK1/GAPDH versus dNT1/GAPDH was 0.669 (p<0.001). [3H]FLT uptake showed negative moderate correlation with dNT1/GAPDH levels (r=-0.563; p<0.01), but no significance with TK1/GAPDH levels. Doubling time had no relationship with the TK1 or dNT1 expression. This study profiled correlative expression of TK1 and dNT1 in cancer cell lines, and showed that dNT1 expression determines the lower uptake of FLT, providing a basis for understanding deoxyribonucleotide metabolism.Anticancer research 06/2011; 31(6):2135-9. · 1.73 Impact Factor -
Article: Early assessment of tumor response to JAC106, an anti-tubulin agent, by 3'-deoxy-3'-[¹⁸F]fluorothymidine in preclinical tumor models.
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ABSTRACT: We determined whether [(18)F]fluorothymidine (FLT) positron emission tomography (PET) can detect early effects on tumor proliferation of JAC106, a new anti-tubulin agent. Inhibition of tubulin polymerization and [(3)H]colchicine binding were assessed in vitro. The effects of JAC106 on cytotoxicity, mitotic arrest, [(18)F]FLT uptake, and thymidine kinase 1 (TK1) activity were examined in SW620 and KB-V1 cells. Dose-dependent antitumor effects of JAC106 were monitored by measuring tumor growth and by dynamic [(18)F]FLT PET imaging in mice bearing SW620 and KB-V1 tumors. The proliferation status of tumors was examined. JAC106 potently inhibited tubulin polymerization and decreased the viability of SW620 (p < 0.001, half maximal inhibitory concentration, IC(50) = 3.15 ± 1.4) and KB-V1 (p < 0.01, IC(50) = 21.84 ± 24.59) cells. Exposure to JAC106 induced mitotic arrest starting at 18 h and dose-dependently increased [(18)F]FLT uptake/1 × 10(5) cells (p < 0.05) and TK1 activity and expression in vitro. Administration of 30 mg/kg JAC106 to mice inhibited the growth of SW620 and KB-VI tumors (%T/C 3.34 and 20.6%, respectively). The baseline standardized uptake values (SUV) of SW620 and KB-V1 tumors were 0.96 ± 0.31 and 2.29 ± 0.70, respectively, with a significant difference (p < 0.01). After 3 days of treatment with 30 mg/kg JAC106, the [(18)F]FLT SUVs of SW620 and KB-V1 tumors, normalized to those before treatment, were 77.9 ± 22.4% (p = 0.059) and 43.2 ± 14.0% (p < 0.01), respectively. JAC106 significantly decreased the number of Ki-67-positive cells, TK1 activity, cell fraction in G(0)G(1) phase, and tumor expression of cyclins E, A, and B1 on day 3. [(18)F]FLT PET can be used to monitor JAC106 inhibition of tumor growth, beginning 3 days after treatment. Incorporation of [(18)F]FLT PET may be useful in the early clinical development of JAC106.European Journal of Nuclear Medicine 04/2011; 38(8):1436-48. · 4.53 Impact Factor -
Article: A randomized, double-blind, multicenter comparison study of triple antiplatelet therapy with dual antiplatelet therapy to reduce restenosis after drug-eluting stent implantation in long coronary lesions: results from the DECLARE-LONG II (Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients with Long Coronary Lesions) trial.
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ABSTRACT: The purpose of this study was to determine whether cilostazol reduces intimal hyperplasia in patients undergoing long zotarolimus-eluting stent implantation (stent length: ≥ 30 mm) for native long coronary lesions (length: ≥ 25 mm). Restenosis after drug-eluting stent implantation remains a significant clinical problem in long coronary lesions. Patients (n = 499) were assigned randomly to triple (aspirin, clopidogrel, and cilostazol, triple group: n = 250) or dual antiplatelet therapy (aspirin and clopidogrel and placebo, dual group: n = 249) for 8 months after long zotarolimus-eluting stent implantation. The primary end point was in-stent late loss at the 8-month angiography according to the intention-to-treat principle. The 2 groups had similar baseline characteristics. The in-stent (0.56 ± 0.55 mm vs. 0.68 ± 0.59 mm, p = 0.045) and in-segment (0.32 ± 0.54 mm vs. 0.47 ± 0.54 mm, p = 0.006) late loss were significantly lower in the triple versus dual group, as were 8-month in-stent restenosis (10.8% vs. 19.1%, p = 0.016), in-segment restenosis (12.2% vs. 20.0%, p = 0.028), and 12-month ischemic-driven target lesion revascularization (5.2% vs. 10.0%, p = 0.042) rates. At 12 months, major adverse cardiac events including death, myocardial infarction, and ischemic-driven target lesion revascularization tended to be lower in the triple group than the dual group (7.2% vs. 12.0%, p = 0.07). Percent intimal hyperplasia volume by volumetric intravascular ultrasound analysis was reduced from 27.1 ± 13.2% for the dual group to 22.1 ± 9.9% for the triple group (p = 0.017). Patients receiving triple antiplatelet therapy after long zotarolimus-eluting stent implantation had decreased extent of late luminal loss, percent intimal hyperplasia volume, and angiographic restenosis, resulting in a reduced risk of 12-month target lesion revascularization compared with patients receiving dual antiplatelet therapy. (Triple Versus Dual Antiplatelet Therapy after ABT578-Eluting Stent; NCT00589927).Journal of the American College of Cardiology 03/2011; 57(11):1264-70. · 14.16 Impact Factor -
Article: The impact of hyperuricemia on in-hospital mortality and incidence of acute kidney injury in patients undergoing percutaneous coronary intervention.
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ABSTRACT: There is very little information about the relationship between hyperuricemia, acute kidney injury (AKI) and in-hospital mortality. With a retrospective analysis of the medical records, 1,247 patients who had percutaneous coronary intervention (PCI) were investigated. AKI was defined as an increase in serum creatinine of ≥0.5mg/dl or ≥50% over baseline within 7 days of PCI. The association of AKI with clinical, biochemical and procedural variables were examined. In addition, the association of hyperuricemia with in-hospital mortality was also examined. Of the 1,247 patients in the study population, 51 (4.1%) experienced AKI after PCI, 15 of whom required hemodialysis. In-hospital mortality occurred in 1.6% (20 of 1,247) in 19.6% (10 of 51) of AKI individuals, and 0.8% (10 of 1,186) of the non-AKI participants (odd ratios, 28.927; 95% confidence intervals, 11.411-73.328; P<0.001). In our study, the most powerful predictors of these variables were acute myocardial infarction, baseline estimated glomerular filtration rate (eGFR) <60 ml·min(-1)·1.73 m(-2), diabetics mellitus, anemia and hyperuricemia. Notably, the incidence of AKI after PCI markedly increased in diabetic or hyperuricemic patients with a baseline eGFR of <60 ml·min(-1)·1.73 m(-2). It is clear that AKI develops due to multiple risk factors. Our results indicate that hyperuricemia is independently associated with an increased risk of in-hospital mortality and AKI in patients treated with PCI.Circulation Journal 01/2011; 75(3):692-7. · 3.77 Impact Factor -
Article: Induction of thymidine kinase 1 after 5-fluorouracil as a mechanism for 3'-deoxy-3'-[18F]fluorothymidine flare.
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ABSTRACT: Imaging the pharmacodynamics of anti-cancer drugs may allow early assessment of anti-cancer effects. Increases in 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) uptake early after thymidylate synthase inhibition (TS) inhibition, the so-called flare response, is considered to be largely due to an increase in binding sites for type-1 equilibrative nucleoside transporter. We investigated the induction of thymidine kinase 1 (TK1) after 5-fluorouracil (5-FU) treatment as one of mechanisms for [(18)F]FLT flare. Exposure of nine cancer cell lines to 5-FU for 24h induced a 2.5- to 3.5-fold increase in [(18)F]FLT uptake, significantly higher than the 1.5-fold increase observed 2h after treatment. The increase of [(18)F]FLT uptake 24h after 5-FU exposure accompanied TK1 induction in most cell lines. In representative cell lines (A431 and HT29), 5-FU time-dependently increased [(18)F]FLT uptake, kinase activity and the levels of protein and mRNA for TK1, sequential cyclin E and A induction, and G(1)-S phase transition. Cycloheximide treatment and knockdown of TK1 completely inhibited 5-FU-induced [(18)F]FLT flare. On the other hand, HCT8 cells showed a biphasic [(18)F]FLT flare with lacked TK1 induction in response to the dosage of 5-FU. Cycloheximide did not inhibit 5-FU-induced [(18)F]FLT flare in this cells. In vivo dynamic [(18)F]FLT-PET and ex vivo analysis in HT29 tumor-bearing mice showed significantly increased [(18)F]FLT flux and TK1 activity of tumor tissue 24h after 5-FU administration (P<0.05). Conclusively, 5-FU induced TK1 and TK1-mediated high [(18)F]FLT flare in most of cell lines. [(18)F]FLT-PET may be used to assess pharmacodynamics of TS inhibitor by a mechanism involving TK1 induction.Biochemical pharmacology 11/2010; 80(10):1528-36. · 4.25 Impact Factor -
Article: An extremely rare variety of anomalous coronary artery: right coronary artery originating from the distal left circumflex artery.
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ABSTRACT: A single coronary artery (SCA) is a rare congenital anomaly of the coronary circulation, which is often associated with myocardial ischemia and other congenital cardiac anomalies. A 77-year-old woman visited our hospital complaining of typical chest pain. Coronary angiography revealed an isolated SCA. The right coronary artery did not originate from the aorta, but instead emerged from the distal left circumflex artery, with significant stenosis at the proximal portion of the left anterior descending artery. A stent was successfully implanted at the culprit lesion. There was no perfusion defect detected by a cardiac SPECT study.Korean Circulation Journal 09/2010; 40(9):465-7. -
Article: Transient complete atrioventricular block associated with curcumin intake.
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ABSTRACT: Curcumin is a polyphenol responsible for the yellow color of turmeric, a curry spice. A large body of evidence showed that curcumin possessed a variety of beneficial activities. We report a case of transient complete atrioventricular block in a 38-year-old man, after intake of curcumin containing pills for on 1 month. Since all other possible causes of conduction disturbance were excluded and causal relation was achieved by re-intake of the same amount of turmeric containing pills, side-effect of the curcumin containing pills was identified as the most likely diagnosis. After cessation of the pills, no further conduction disturbances and associated symptoms were noticed for the ensuing 6 months since discharge.International journal of cardiology 11/2009; 150(2):e50-2. · 7.08 Impact Factor -
Article: The association between left ventricular hypertrophy and biomarkers in patients on continuous ambulatory peritoneal dialysis.
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ABSTRACT: Left ventricular hypertrophy (LVH) is a major cardiovascular complication and an important predictor of mortality in patients with end stage renal disease. Some studies have shown that the serum aldosterone levels are correlated with LVH in non-diabetic patients undergoing hemodialysis. The objective of this study was to elucidate the relationships between serum biomarkers, including aldosterone, and echocardiographic findings, such as LVH, in patients on peritoneal dialysis. Thirty patients on continuous ambulatory peritoneal dialysis (CAPD) for >12 months at Soonchunhyang University Cheonan Hospital were included. Transthoracic echocardiography was performed and the left ventricular mass index (LVMI) was calculated using the Devereux formula. Serum biomarkers {N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin T, C-reactive protein, renin, and aldosterone} were measured. Sixteen of 30 patients had LVH on the basis of the LVMI. The mean serum aldosterone level was 62.53+/-60.73 pg/mL (range, 5.03-250.68 pg/mL). LVH, on the basis of the LVMI, was not correlated with the serum aldosterone level. The serum aldosterone levels were not associated with echocardiographic findings, even with co-existing diabetes mellitus. The LVMI had a negative correlation with the hemoglobin (r=-0.405, p=0.029) and hematocrit (r=-0.374, p=0.042), and a positive correlation with NT-proBNP (r=0.560, p=0.002). The other biomarkers (renin, aldosterone, troponin T, and C-reactive protein) were not correlated with the LVMI. The LVMI was correlated with the left atrium volume index (r=0.675, p<0.001). NT-proBNP is a good marker to predict LVH in patients undergoing CAPD. The serum aldosterone level is not correlated with LVMI, even with co-existing diabetes mellitus.Korean Circulation Journal 11/2009; 39(11):488-93. -
Article: Reproducibility of the kinetic analysis of 3'-deoxy-3'-[(18)F]fluorothymidine positron emission tomography in mouse tumor models.
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ABSTRACT: We assessed the reproducibility of the kinetic analysis of 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) positron emission tomography (PET) in A431 human epidermoid carcinoma and murine Lewis lung carcinoma (LLC) tumor models. We injected 7.4 MBq of FLT (n=10 for each group) and acquired 2-h dynamic PET images. A second scan was performed 1 day later. We calculated standardized uptake value (SUV), kinetic rate constants, volume of distribution of phosphorylated FLT (V(dm)), net influx constant (K(FLT-CA)) and influx constant by Patlak graphical analysis (K(FLT-PA)). The percent difference between measurements of a parameter was calculated to compare the reproducibilities of different parameters. FLT phosphorylation was higher in mice with A431 tumors than in mice with LLC tumors (P<.005). Differences in the standard deviations of the percent differences of parameters were statistically significant (P<.001) in each model. In mice with A431 tumors, SUV, V(dm), K(FLT-CA) and K(FLT-PA) had standard deviations of the percent difference of < or = 20%. The most reproducible parameter was K(FLT-PA), although the standard deviation (15.6%) was not statistically different from those of V(dm) (15.8%), K(FLT-CA) (17.5%) and SUV (18.9%). In mice with LLC tumors, K(1), K(1)/k(2) and k(3) had standard deviations of the percent difference of < or = 20%. No macroparameters reflecting a total FLT flux had standard deviations of < or = 20%. Our results show the reproducibility of the kinetic macroparameters of FLT PET in mouse tumors with high FLT phosphorylation.Nuclear Medicine and Biology 10/2009; 36(7):711-9. · 3.02 Impact Factor -
Article: Coronary artery thrombosis associated with Paclitaxel in advanced ovarian cancer.
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ABSTRACT: A 63-year-old woman was diagnosed with ovarian cancer and peritoneal carcinomatosis. The day after paclitaxel was administered, an acute myocardial infarction occurred. Emergency coronary angiography revealed a filling defect in the left main coronary artery and total occlusion in the distal left anterior descending coronary artery, with no luminal irregularity or narrowing. Intravascular ultrasonography showed no significant plaque in the left main coronary artery. A thrombophilia work-up was negative, and the patient was treated with tirofiban, clopidogrel, and aspirin. The follow-up coronary angiogram showed that the occlusion of the distal obtuse marginal branch and distal left anterior descending artery had cleared. Paclitaxel has been associated with acute myocardial infarction. However, the pathogenesis of myocardial infarction associated with paclitaxel is not known. This case raises the possibility that paclitaxel can induce coronary artery thrombosis, resulting in myocardial infarction.Korean Circulation Journal 03/2009; 39(3):124-7. -
Article: Kinetic modeling of 3'-deoxy-3'-18F-fluorothymidine for quantitative cell proliferation imaging in subcutaneous tumor models in mice.
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ABSTRACT: 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a thymidine analog that was developed for measuring tumor proliferation with PET. The aim of this study was to establish a kinetic modeling analysis method for quantitative (18)F-FLT PET studies in subcutaneous tumor models in mice. To explore the validity of an image-derived left ventricular input function, we measured equilibrium constants for plasma and whole blood and metabolite fractions in blood after (18)F-FLT injection. In parallel, dynamic (18)F-FLT PET scans were acquired in 24 mice with a small-animal dedicated PET scanner to compare arterial blood activities obtained by PET and blood sampling. We then investigated kinetic models for (18)F-FLT in human epithelial carcinoma (A431) and Lewis lung carcinoma tumor models in mice. Three-compartment models with reversible phosphorylation (k(4) not equal 0, 3C5P) and irreversible phosphorylation (k(4) = 0, 3C4P) and a 2-compartment model (2C3P) were examined. The Akaike information criterion and F statistics were used to select the best model for the dataset. Gjedde-Patlak graphic analysis was performed, and standardized uptake values in the last frame were calculated for comparison purposes. In addition, quantitative PET parameters were compared with Ki-67 immunostaining results. (18)F-FLT equilibrated rapidly (within 30 s) between plasma and whole blood, and metabolite fractions were negligible during PET scans. A high correlation between arterial blood sampling and PET data was observed. For 120-min dynamic PET data, the 3C5P model best described tissue time-activity curves for tumor regions. The net influx of (18)F-FLT (K(FLT)) and k(3) obtained with this model showed reasonable intersubject variability and discrimination ability for tumor models with different proliferation properties. The K(FLT) obtained from the 60- or 90-min data correlated well with that obtained from the 120-min data as well as with the Ki-67 results. The image-derived arterial input function was found to be feasible for kinetic modeling studies of (18)F-FLT PET in mice, and kinetic modeling analysis with an adequate compartment model provided reliable kinetic parameters for measuring tumor proliferation.Journal of Nuclear Medicine 12/2008; 49(12):2057-66. · 6.38 Impact Factor
Top co-authors
Top Journals
Institutions
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2010–2012
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Asan Medical Center
Seoul, Seoul, South Korea -
Soonchunhyang University
Tenan, South Chungcheong, South Korea
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2009–2012
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Ulsan University Hospital
Ulsan, Ulsan, South Korea
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2008
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Seoul National University
- Department of Nuclear Medicine
Seoul, Seoul, South Korea
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