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Byung-Tae Kim

Publications and source records attributed to Byung-Tae Kim.

At least 37 records · Page 2Linked to original sources
PubMed2006

Evidence that myocardial Na/I symporter gene imaging does not perturb cardiac function.

UNLABELLED: Adenoviral Na/I symporter (NIS) gene transfer has emerged as a promising method for myocardial gene imaging but concern over possible perturbation of cardiac function persists. In this study, we addressed this issue with cultured cardiac cells and serial echocardiography, creatine kinase (CK) measurements, and histologic examination of rats intramyocardially injected with an adenovirus that expresses both NIS and enhanced green fluorescent protein (EGFP) (Ad.EGFP.NIS) or a control virus (Ad.EGFP). METHODS: H9C2 cardiac myoblasts differentiated into cardiomyocytes were evaluated for the effect of Ad.EGFP.NIS and Ad.EGFP infection on viable cell number and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Rats injected intramyocardially with 3 x 10(8) plaque-forming units of Ad.EGFP.NIS (n = 9) or Ad.EGFP (n = 8) underwent serial echocardiographic measurements of heart rate, left ventricular (LV) dimensions, ejection fraction (EF), and fractional shortening (FS) on the day before and on days 4 and 9 after gene transfer. Five Ad.EGFP.NIS rats also underwent repeated (123)I imaging from which ratios of cardiac to mediastinal counts (C/M ratios) were obtained. Separate rats underwent serial measurements of serum CK, myocardial myeloperoxidase assays, and microscopic assessment of inflammation. RESULTS: Cultured cardiac cells showed no change in cell viability or proliferation at 4 and 9 d after Ad.EGFP.NIS or Ad.EGFP infection compared with controls. (123)I scintigraphy demonstrated high cardiac radiouptake at Ad.EGFP.NIS injection sites by days 2 and 4 (C/M ratios, 5.0 +/- 0.6 and 5.1 +/- 1.0, respectively), followed by a complete loss of uptake by day 9 (C/M ratio, 1.4 +/- 0.0). Serial echocardiography revealed no difference in heart rate, LV dimensions, or functional parameters between Ad.EGFP.NIS and Ad.EGFP groups at any given time. Mild reductions in LVEF and LVFS by day 9 compared with baseline were similar for both Ad.EGFP (88.2% +/- 6.4% vs. 79.6% +/- 5.0% for LVEF and 0.55 +/- 0.10 vs. 0.44 +/- 0.05 for LVFS) and Ad.EGFP.NIS groups (88.0% +/- 5.4% vs. 78.7% +/- 4.6% for LVEF and 0.54 +/- 0.09 vs. 0.42 +/- 0.05 for LVFS). Serial serum CK and myocardial myeloperoxidase activities were not elevated in either group, in contrast to substantial increases found after ischemia-reperfusion injury. Histology revealed similar mild inflammatory cell infiltration restricted to the injection site for both groups. CONCLUSION: The results of this study demonstrate that myocardial NIS gene imaging does not cause significant myocardial injury or perturbed cardiac function, other than mild effects likely due to adenoviral vector-associated host response. Thus, this practical and convenient reporter gene strategy can be used safely for noninvasive myocardial gene imaging in living subjects.

Adenoviridae↗
PubMed2005

Improved detection of second primary cancer using integrated [18F] fluorodeoxyglucose positron emission tomography and computed tomography for initial tumor staging.

PURPOSE: This study evaluated prospectively the value of integrated whole-body positron emission tomography and computed tomography (PET/CT) using [18F] fluorodeoxyglucose (FDG) in detecting a second primary cancer at the time of the initial staging in comparison with a conventional staging work-up (CSW). METHODS: The participants were 547 patients diagnosed with cancer who underwent FDG PET/CT imaging for the initial staging. An additional diagnostic evaluation was performed when there were abnormal findings indicative of a second primary cancer on either PET/CT or CSW considering the site and the biologic behavior of the alleged primary tumor. RESULTS: A total of 27 second primary malignant tumors were identified in 26 of the 547 patients (4.8%). FDG PET/CT found 45 lesions indicative of a second primary cancer, of which 24 lesions were proved to be a second primary cancer, seven were clinically unexpected metastases, and 14 lesions were benign. Therefore, sensitivity and positive predictive value of FDG PET/CT in detecting a second primary cancer or an unexpected metastasis were 91% (31 of 34) and 69% (31 of 45), respectively. In contrast, CSW could not identify 16 second primary cancers and one metastatic lesion. CONCLUSION: FDG PET/CT at the time of the initial staging is useful for screening a second primary cancer with a high sensitivity. An additional diagnostic work-up is essential when abnormal findings, which are indicative of a second primary cancer, are obtained on PET/CT images to rule out the presence of either a second primary cancer or an unexpected metastasis.

Aged↗
PubMed2005

Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging.

PURPOSE: To evaluate prospectively the accuracy of integrated positron emission tomography (PET) and computed tomography (CT) with use of fluorodeoxyglucose (FDG), compared with that of stand-alone CT, for the preoperative staging of non-small cell lung cancer, with surgical and histologic findings used as the reference standard. MATERIALS AND METHODS: Institutional review board approval and patient informed consent were obtained. From November 2003 to February 2004, 106 patients (78 men, 28 women; mean age, 56 years) with non-small cell lung cancer underwent curative surgical resection (tumor resection and lymph node dissection) after stand-alone CT followed by integrated FDG PET/CT. Tumor stages were determined by using the TNM and American Joint Committee on Cancer staging systems. Histopathologic results served as the reference standard. Statistically significant differences in tumor staging between integrated PET/CT and stand-alone CT were determined with P < .05 obtained by using the McNemar test or with a generalized estimating equation. RESULTS: The primary tumor was correctly staged in 84 patients (79%) at stand-alone CT and in 91 patients (86%) at integrated FDG PET/CT (P = .25). For the depiction of malignant nodes, the sensitivity, specificity, and accuracy of CT were 70% (23 of 33 nodal groups), 69% (248 of 360), and 69% (271 of 393), respectively, whereas those of PET/CT were 85% (28 of 33), 84% (302 of 360), and 84% (330 of 393) (P = .25, P < .001, and P < .001, respectively). There were 112 false-positive interpretations at CT for 54 hilar, 16 subcarinal, 29 paratracheal, 10 subaortic, and two pulmonary ligament nodal groups and one upper paratracheal group, compared with only 58 false-positive interpretations at PET/CT for 32 hilar, seven subcarinal, 13 lower paratracheal, and six subaortic nodal groups. There were 10 false-negative interpretations at CT for four hilar, two lower paratracheal, and two subcarinal nodal groups, one prevascular and retrotracheal group, and one inferior pulmonary group, but only five false-negative interpretations at PET/CT (one each for paratracheal, subaortic, subcarinal, inferior pulmonary, and hilar nodal groups). CONCLUSION: Integrated FDG PET/CT is significantly better than stand-alone CT for lung cancer staging and provides enhanced accuracy and specificity in nodal staging.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Simple devices for dispensing [18F]FDG.

High dose [18F]FDG is prepared routinely using an automated synthesizer. Accordingly, an automated dispenser is needed to dispense [18F]FDG at the desired dose while reducing the operator's radiation exposure, and no dispenser capable of vial-to-vial and vial-to-syringe dispensing in one system is commercially available. Here, we describe simple devices for the vial-to-vial and vial-to-syringe dispensing of [18F]FDG.

Fluorodeoxyglucose F18↗
PubMed2005

Synthesis and evaluation of 2-[18F]fluoro-CP-118,954 for the in vivo mapping of acetylcholinesterase.

5,7-Dihydro-3-[2-[1-(2-fluorobenzyl)-4-piperidinyl]ethyl]-6H-pyrrolo[3,2,f]-1,2-benzisoxazol-6-one (2-flouro-CP-118,954; 1), a potent acetylcholinesterase (AChE) inhibitor, was prepared as a radioligand by reductive alkylation of CP-144,885 the debenzylated form of CP 118,954, with 2-[18F]fluorobenzaldehyde. The decay-corrected radiochemical yield was 25-30% and the effective specific activity was 41-53 GBq/micromol. Tissue distribution studies of 2-[18F]fluoro-CP-118,954 ([18F]1) in mice showed that the regional brain distribution correlated well with the known density of AChE in the mouse brain. A high level of uptake in the striatum was also shown at all time points in the olfactory tubercle, which is known to have dopaminergic neurons. Blocking studies showed that radioligand uptake in all brain regions was not altered by either the dopamine receptor antagonists or the sigma receptor agonist. On the other hand, radioligand uptake in both the striatum and the olfactory tubercle was significantly blocked (80%) by ligand 1. The low level of bone uptake over time suggested that [18F]1 underwent little in vivo metabolic defluorination. The lack of metabolite formation in the mouse brain indicated that the regional distribution was attributed to [18F]1. These results demonstrated that [18F]1 binds specifically and selectively to AChE in mice and appears to be a suitable radioligand for the in vivo mapping of AChE.

Acetylcholinesterase↗
PubMed2005

PMA-enhanced neutrophil [18F]FDG uptake is independent of integrin occupancy but requires PI3K activity.

OBJECTIVE: While respiratory burst enhances neutrophil glucose utilization, many neutrophil functions are critically influenced by extracellular matrix interaction and phosphoinositide-3-OH kinase (PI3K) signaling. We thus evaluated the role of RGD integrin occupancy and PI3K inhibition on respiratory burst and [(18)F]fluorodeoxyglucose ([(18)F]FDG) uptake of stimulated neutrophils. METHODS: Human neutrophils were stimulated by 100 ng/ml phorbol-myristate-acetate (PMA), and respiratory burst was measured by cumulative luminescence with lucigenin. [(18)F]FDG uptake and total hexokinase activity was measured 20 min after PMA stimulation in the presence or absence of soluble RGD peptides (200 microg/ml) and/or the PI3K inhibitor wortmannin (200 nM). RESULTS: Phorbol-myristate-acetate induced a 71.7+/-0.9 fold increase in neutrophil oxygen intermediate generation. [(18)F]FDG uptake was increased to 194.6+/-3.7% and hexokinase activity to 145.0+/-2.0% of basal levels (both P<.0005). RGD peptides attenuated respiratory burst activation to 35.6+/-0.2% (P<.005) but did not inhibit stimulated [(18)F]FDG uptake or hexokinase activity. In contrast, without affecting respiratory burst activation, wortmannin inhibited PMA-stimulated [(18)F]FDG uptake to 66.9+/-1.6% and hexokinase activity to 81.0+/-4.2% (both P<.0005), demonstrating its dependence on PI3K activity. Neither RGD nor wortmannin reversed the other's inhibitory effect on stimulated [(18)F]FDG uptake and hexokinase activity or respiratory burst, which suggests the involvement of distinct signaling pathways. CONCLUSION: Neutrophil [(18)F]FDG uptake is enhanced by PMA through a mechanism that requires PI3K activity but is independent of integrin receptor occupancy or respiratory burst activation.

Acridines↗
PubMed2005

Distribution and pharmacokinetic analysis of angiostatin radioiodine labeled with high stability.

OBJECTIVE: Radiotracers of anticancer agents provide important information on its in vivo handling. Angiostatin (AST) is a promising anticancer drug with potent antiangiogenic effects, but reported AST radiotracers suffer from poor in vivo stability. In this study, we synthesized an AST probe radioiodinated via the Bolton-Hunter reagent (125I-BH-AST) and investigated its stability and biokinetics in mice. METHODS: 125I-BH-AST and conventional direct radioiodinated 125I-AST were evaluated for human endothelial cell binding characteristics. In vivo stability of the radiotracers was compared by biodistribution studies in normal ICR mice. Angiostatin pharmacokinetics was analyzed by serial blood sampling after intravenous injection of 125I-BH-AST with varying AST concentrations in mice. RESULTS: Both 125I-AST and 125I-BH-AST retained selective endothelial binding as demonstrated by dose-dependent inhibition by nonradiolabeled AST. 125I-BH-AST was substantially more stable in mice than 125I-AST, with 28- and 7-fold lower 24-h thyroid and blood activities, respectively (15.5+/-1.5 vs. 430.9+/-32.2 and 0.1+/-0.0 vs. 0.8+/-0.0 %ID/g; both P<.005). Using (125)I-BH-AST, we found that 24-h AST accumulation was highest in the kidneys, followed by the liver and lungs. Kinetic analysis of 125I-BH-AST revealed AST to have linear pharmacokinetics with a T(1/2) of 5.8+/-2.6 h, volume of distribution (V(d)) of 6.8+/-1.3 ml and clearance of 0.8+/-0.1 ml/h. CONCLUSION: Radioiodine-labeled AST prepared by the BH method provides a radioprobe with superior stability and improved in vivo biokinetics that is useful for distribution and pharmacokinetic studies.

Angiostatins↗
PubMed2005

Nitric oxide stimulates 18F-FDG uptake in human endothelial cells through increased hexokinase activity and GLUT1 expression.

UNLABELLED: The endothelium constitutes a functionally active organ critically involved in angiogenesis. Nitric oxide (NO) is an important regulator of vascular homeostasis and angiogenesis and stimulates glucose metabolism in certain cells. We thus investigated the effect of exogenous NO on (18)F-FDG transport in human endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with the NO donors sodium nitroprusside (SNP) or diethylenetriamine (DETA), in concentrations of 1 micromol/L-1 mmol/L for up to 24 h. (18)F-FDG uptake levels corrected for protein content were determined by cellular radioactivity measured after 30-min incubation. Cells were evaluated for total hexokinase activity and plasma membrane glucose transporter 1 (GLUT1) levels, and involvement of potential signaling pathways was investigated by cotreatment with respective protein kinase inhibitors. RESULTS: Both SNP and DETA stimulated HUVEC (18)F-FDG uptake, which began at 16 h and peaked at 24 h. The increase in (18)F-FDG uptake was dose dependent, reaching 464.0% +/- 49.8% and 254.5% +/- 10.8% of control levels at 24 h with 1 mmol/L SNP and DETA, respectively. Exposure of HUVECs to 1 mmol/L SNP resulted in a 3.5 +/- 0.3-fold elevation in hexokinase activity (P < 0.01) and a significant increase in GLUT1 levels. SNP-stimulated (18)F-FDG uptake was abolished by cotreatment with cycloheximide, the tyrosine kinase inhibitor genistein, the phosphatidylinositol-3 kinase (PI3K) inhibitor wortmannin, or the protein kinase C inhibitor staurosporine. CONCLUSION: NO stimulates (18)F-FDG uptake in HUVECs through an increase in GLUT1 expression and hexokinase activity, which appears to involve both protein kinase C and PI3K pathways.

Cells, Cultured↗
PubMed2005

Radiolabeled RGD uptake and alphav integrin expression is enhanced in ischemic murine hindlimbs.

UNLABELLED: Radiolabeled RGD peptides that target alpha(v)beta3 integrin are promising tracers for imaging tumor angiogenesis. Integrins and angiogenesis also play important roles in healing of ischemic lesions. Thus, we investigated the biodistribution of radiolabeled RGD and expression of alpha(v) integrin in a mouse model of hindlimb ischemia. METHODS: 125I-3-Iodo-D-Tyr4-cyclo(-Arg-Gly-Asp-D-Tyr-Val-) (125I-c(RGD(I)yV)) was synthesized and tested for endothelial binding. Hindlimb ischemia was induced in ICR mice through femoral artery ablation, and perfusion was measured with laser Doppler blood flowmetry. 125I-c(RGD(I)yV) biodistribution was evaluated in control animals (n = 7) and ischemic models on day 3, 8, or 14 (n = 6 each). Control experiments were performed using a radiolabeled peptide with a scrambled amino acid sequence (125I-GfVGV). Microsections of hindlimb tissue were immunostained for alpha(v) integrin expression and stained with alkaline phosphatase to localize vascular endothelial cells. RESULTS: 125I-c(RGD(I)yV) retained specific binding to human umbilical vein endothelial cells. Perfusion in ischemic hindlimbs immediately fell to 10% +/- 4% of contralateral levels and gradually recovered to 22% +/- 11% and 64% +/- 9% on days 8 and 14, respectively. 125I-c(RGD(I)yV) uptake in ischemic muscles significantly increased from a control level of 0.16 +/- 0.05 %ID/g (percentage injected dose per gram of tissue) to 0.85 +/- 0.76 %ID/g at day 3, 0.43 +/- 0.23 %ID/g at day 8, and 0.43 +/- 0.28 %ID/g at day 14 (all P < 0.05). Ischemic muscle-to-lung count ratios had a virtually identical trend: 0.42 +/- 0.25 for controls, 2.34 +/- 1.70 at day 3 (P < 0.02), 1.46 +/- 0.52 at day 8 (P < 0.001), and 1.39 +/- 0.94 at day 14 (P < 0.02). In contrast, uptake of the control peptide in ischemic hindlimbs was not different from that of controls. Immunohistochemistry revealed substantially increased alpha(v) integrin staining in ischemic hindlimb tissue. CONCLUSION: Radioiodine RGD uptake is significantly enhanced in ischemic hindlimbs of a mouse model, and is accompanied by an increase in alpha(v) integrin expression. Further investigation is thus warranted to illuminate the potential role of radiolabeled RGD for noninvasive monitoring of peripheral ischemic lesions.

Animals↗
PubMed2005

Accuracy of myocardial sodium/iodide symporter gene expression imaging with radioiodide: evaluation with a dual-gene adenovirus vector.

UNLABELLED: The sodium/iodide symporter (NIS) gene allows convenient reporter imaging with gamma-cameras and free radioiodide. In this study, we investigated the accuracy of this technique for assessing myocardial gene expression in living rats by using a dual-gene adenovirus that expresses both NIS protein and enhanced green fluorescent protein (EGFP). METHODS: Rats underwent myocardial injection with the dual-gene adenovirus (Ad.EGFP.NIS) or a control virus (Ad.EGFP). 123I scintigraphy was performed at day 4, and ratios of cardiac counts to mediastinal count were measured. The site of radiouptake was localized by use of dual-isotope 201Tl images, and radioiodide efflux rates were evaluated by dynamic imaging. The dependence of cardiac radiouptake on viral titers and the sensitivity of detection of cardiac radiouptake were investigated at various viral titers. The radioactivity, EGFP, and NIS protein expression sites were compared microscopically. The correlation of image-based uptake with fluorometric measurements of EGFP concentrations was assessed by regression analysis. RESULTS: 123I scintigraphy demonstrated clear focal myocardial uptake at the Ad.EGFP.NIS injection site, with relatively slow washout rates (3.3% +/- 0.8%/h), despite the absence of organification. Image-based cardiac uptake increased in a viral titer-dependent manner, with a detection threshold of between 3 x 10(6) and 1 x 10(7) plaque-forming units. Western blotting showed titer-dependent increases in myocardial NIS protein expression. Tissue radioactivity levels approached 12.5-fold control levels and correlated closely with image-based uptake (r = 0.91; P < 0.0001). Histologic analysis confirmed the colocalization of radiouptake, EGFP fluorescence, and NIS staining. Image-based uptake showed a strong correlation with fluorometric measurements of myocardial EGFP concentrations (r = 0.81; P < 0.0001). CONCLUSION: Our results demonstrate that convenient myocardial gene imaging with gamma-cameras and radioiodide is feasible with the NIS gene. Moreover, the use of this technique with a dual-gene vector appears to allow accurate assessment of the level of myocardial expression of a second gene of interest.

Adenoviridae↗
PubMed2005

Effects of anesthetic agents and fasting duration on 18F-FDG biodistribution and insulin levels in tumor-bearing mice.

UNLABELLED: Small-animal PET has opened the way for imaging (18)F-FDG uptake in murine tumor models, but the need for anesthesia raises concern over its potential influence on (18)F-FDG kinetics. We thus investigated such effects on cultured cells and on tumor-bearing mice after short- and long-term fasting. METHODS: Lewis lung carcinoma (LLC) cells and cardiomyoblasts were treated for 2 h with a 100 micromol/L concentration of xylazine, ketamine, xylazine plus ketamine (Xy/Ke), or pentobarbital and were measured for (18)F-FDG uptake. LLC tumor-bearing C57BL6 mice that had been kept fasting for either 4 or 20 h were injected with Xy/Ke, pentobarbital, or saline and were administered 1.8 MBq of (18)F-FDG 15 min later. Biodistribution studies and plasma glucose and insulin assays were performed 45 min after injection. Separate anesthetized and control mice underwent (18)F-FDG PET. RESULTS: (18)F-FDG uptake in LLC cells was unaffected by anesthetic agents, whereas xylazine and ketamine caused a small increase of uptake in cardiomyoblasts. In mice kept fasting 4 h, Xy/Ke induced a marked elevation of (18)F-FDG activity (percentage injected dose [%ID]) in blood (6.8 +/- 0.9%ID/g vs. 1.1 +/- 0.6%ID/g) and kidneys while decreasing myocardial uptake (2.3 +/- 1.3%ID/g vs. 4.7 +/- 1.8%ID/g). Target-to-blood ratios were significantly reduced. Pentobarbital caused a moderate increase in blood activity (2.5 +/- 0.8%ID/g), decreased myocardial uptake (2.8 +/- 0.5%ID/g), and reduced target-to-blood ratios. PET images of mice kept fasting 4 h were consistent with the biodistribution data. Insulin levels were lower with Xy/Ke and higher with pentobarbital. In mice kept fasting 20 h, Xy/Ke and pentobarbital increased blood (18)F-FDG activity (5.5 +/- 2.2 and 4.9 +/- 0.9%ID/g vs. 2.4 +/- 0.3%ID/g) and reduced target-to-blood ratios, but these changes were substantially attenuated, compared with those in mice kept fasting 4 h. In addition, insulin levels were low and unaffected by anesthesia. CONCLUSION: Xy/Ke anesthesia markedly elevates blood (18)F-FDG activity and reduces tumor uptake ratios through inhibition of insulin release in mice kept fasting 4 h, whereas pentobarbital induces a similar but less severe response through insulin resistance. These metabolic effects, however, are substantially attenuated after 20 h of fasting. Hence both the choice of anesthetic and the duration of fasting have important effects on (18)F-FDG kinetics and PET images of tumor-bearing mice and should be considered when such studies are performed.

Anesthetics↗
PubMed2004

Performance improvement of small gamma camera using NaI(Tl) plate and position sensitive photo-multiplier tubes.

The purpose of this study was to improve the performance of a small gamma camera, utilizing a NaI(Tl) plate and a 5" position sensitive PMT. We attempted to build a NaI(Tl) plate crystal system which retained all its advantages, while at the same time integrating some of the advantages inherent in an array-type scintillation crystal system. Flood images were obtained with a lead hole mask, and position mapping was performed by detecting hole positions in the flood image. Energy calibration was performed using the energy spectra obtained from each hole position. Flood correction was performed using a uniformity correction table containing the relative efficiency of each image element. The spatial resolution was improved about 16% after correction at the centre field of view. Resolution deterioration at the outer field of view (OFOV) was considerably ameliorated, from 6.7 mm to 3.2 mm after correction. The sensitivity at the OFOV was also increased after correction, from 0.7 cps microCi(-1) to 2.0 cps microCi(-1). The correction also improved uniformity, from 5.2% to 2.1%, and linearity, from 0.5 mm to 0 mm. The results of this study indicate that the revised correction method can be employed to considerably improve the performance of a small gamma camera using a NaI(Tl) plate-type crystal. This method also provides high spatial resolution and linearity, like array-type crystals do, while retaining the specific advantages of plate-type crystals.

Electronics, Medical↗
PubMed2004

Synthesis and evaluation of fluorine-substituted 1H-pyrrolo[2,3-b]pyridine derivatives for dopamine D4 receptor imaging.

Seven fluorine-substituted 1H-pyrrolo[2,3-b]pyridine derivatives were synthesized based on a lead ligand, 3-[[4-(4-iodophenyl)piperazin-1-yl]-methyl]-1H-pyrrolo[2,3-b]pyridine (L-750,667) and evaluated as potential dopamine D(4) receptor imaging agents by positron emission tomography (PET). Binding affinities of these ligands for the dopamine D(2), D(3), and D(4) receptor subtypes were measured in vitro. Most ligands showed high and selective binding for the D(4) receptor. Ligand 7 had high affinity for the D(4) receptor, whereas ligands 1, 2, and 6 showed high selectivity for the D(4) receptor. LogP values were calculated for the ligands in this series and ligand 6 had the lowest lipophilicity. (18)F-labeled ligand 7 demonstrated a uniform regional brain distribution and a rapid washout in mice, probably due to nonspecific binding. Based on their in vitro binding properties and calculated logP values, ligand 6 appears to have the most promise for dopamine D(4) receptor imaging.

Animals↗
PubMed2004

Characterization of dual layer phoswich detector performance for small animal PET using Monte Carlo simulation.

A positron emission tomograph dedicated to small animal imaging should have high spatial resolution and sensitivity, and dual layer scintillators have been developed for this purpose. In this study, simulations were performed to optimize the order and the length of each crystal of a dual layer phoswich detector, and to evaluate the possibility of measuring signals from each layer of the phoswich detector. A simulation tool GATE was used to estimate the sensitivity and resolution of a small PET scanner. The proposed scanner is based on dual layer phoswich detector modules arranged in a ring of 10 cm diameter. Each module is composed of 8 x 8 arrays of phoswich detectors consisting of LSO and LuYAP with a 2 mm x 2 mm sensitive area coupled to a Hamamatsu R7600-00-M64 PSPMT. The length of the front layer of the phoswich detector varied from 0 to 10 mm at 1 mm intervals, and the total length (LSO + LuYAP) was fixed at 20 mm. The order of the crystal layers of the phoswich detector was also changed. Radial resolutions were kept below 3.4 mm and 3.7 mm over 8 cm FOV, and sensitivities were 7.4% and 8.0% for LSO 5 mm-LuYAP 15 mm, and LuYAP 6 mm-LSO 14 mm phoswich detectors, respectively. Whereas, high and uniform resolutions were achieved by using the LSO front layer, higher sensitivities were obtained by changing the crystal order. The feasibilities for applying crystal identification methods to phoswich detectors consisting of LSO and LuYAP were investigated using simulation and experimentally derived measurements of the light outputs from each layer of the phoswich detector. In this study, the optimal order and lengths of the dual layer phoswich detector were derived in order to achieve high sensitivity and high and uniform radial resolution.

Animals↗
PubMed2004

Synthesis of 7'-[123I]iodo-D-luciferin for in vivo studies of firefly luciferase gene expression.

D-(-)-2-(6'-hydroxy-7'-[(123)I]iodobenzothiazolyl)-delta(2)-thiazoline-4-caroxylic acid (7'-[(123)I]iodo-D-luciferin) was synthesized as a novel reporter probe for in vivo studies of firefly luciferase gene expression. 7'-Iodo-D-luciferin, a nonradioactive standard, was synthesized and showed the binding property (K(M)=4.28 microM) similar to that of D-luciferin (2.53 microM) for firefly luciferase in luminescence assay.

Animals↗
PubMed2004

Identification of proximal left anterior descending artery stenosis with thallium-201 defect patterns in patients with angina pectoris.

We determined the accuracy of perfusion defect patterns in predicting the presence of proximal left anterior descending (LAD) artery stenosis in patients with angina pectoris. The development population consisted of 80 patients with single-vessel LAD stenosis and reversible LAD territory defects on thallium-201 tomography. The types of defect patterns associated with angiographic proximal LAD stenosis in this population were categorized as "proximal LAD patterns." The accuracy of these patterns for identifying proximal LAD stenosis was evaluated in a separate validation population of 152 patients with angina pectoris. The development population demonstrated LAD territory defects of type I (most of the LAD territory; n = 12); type II (apex, apicoanterior, and most of the septum; n = 26), type III (septum; n = 19); type IV (anteroseptum; n = 6); type V (apex; n = 10); and type VI patterns (anterolateral wall; n = 7). Patients with type I, II, and IV patterns were highly associated with proximal LAD stenosis (38 of 44 segments), whereas those with type III, V, and VI patterns were mostly related to distal LAD disease (29 of 36 segments). In the validation population, proximal LAD patterns had a sensitivity, specificity, and accuracy of 72%, 95%, and 91%, respectively, for identifying patients with proximal LAD stenosis. Test sensitivity was 86% when patients without LAD territory defects were excluded from analysis. Results were virtually identical in the subgroup of 84 patients with stable angina. Thus, recognition of LAD territory thallium defect patterns is useful for identifying patients with angina who are likely to have proximal LAD stenosis.

Aged↗
PubMed2004

Synthesis of radioiodine labeled dibenzyl disulfide for evaluation of tumor cell uptake.

Benzyl 4-halobenzyl and ally benzyl disulfide were synthesized as diallyl disulfide analogues and their tumor growth inhibitory effects on the cancer cells (SNU C5 and MCF-7) were comparable to that of diallyl disulfide, indicating that the disulfide functional group was responsible for the tumor growth inhibitory effects. Cu(I)-assisted radioiodination of benzyl 4-bromobenzyl disulfide gave benzyl 4-[123I/125I]iodobenzyl disulfide in 30-40% radiochemical yield. The radiolabeled disulfide was taken up by the cancer cells in a time-dependent manner, and the uptake was inhibited by the pretreatment of S-methyl methanethiosulfonate (MMTS), phorone and diallyl disulfide. This study suggested that the radiolabeled dibenzyl disulfide was taken up by the cancer cells via thiol-disulfide exchange and retained inside the cells.

Antineoplastic Agents↗