• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.386-394
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• 2019

Trypanosoma cruzi infection results in debilitating cardiomyopathy, which is a major cause of mortality and morbidity in the endemic regions of Chagas disease (CD). The pathogenesis of Chagasic cardiomyopathy (CCM) has been intensely studied as a chronic inflammatory disease until recent observations reporting the role of cardio-metabolic dysfunctions. In particular, we demonstrated accumulation of lipid droplets and impaired cardiac lipid metabolism in the hearts of cardiomyopathic mice and patients, and their association with impaired mitochondrial functions and endoplasmic reticulum (ER) stress in CD mice. In the present study, we examined whether treating infected mice with an ER stress inhibitor can modify the pathogenesis of cardiomyopathy during chronic stages of infection. T. cruzi infected mice were treated with an ER stress inhibitor 2-Aminopurine (2AP) during the indeterminate stage and evaluated for cardiac pathophysiology during the subsequent chronic stage. Our study demonstrates that inhibition of ER stress improves cardiac pathology caused by T. cruzi infection by reducing ER stress and downstream signaling of phosphorylated eukaryotic initiation factor ($P-elF2{\alpha}$) in the hearts of chronically infected mice. Importantly, cardiac ultrasound imaging showed amelioration of ventricular enlargement, suggesting that inhibition of ER stress may be a valuable strategy to combat the progression of cardiomyopathy in Chagas patients.

• The Korean Journal of Pain
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• v.34 no.4
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• pp.427-436
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• 2021

Background: Pharmacological and non-pharmacological therapies have been used to treat patients with chemotherapy-induced peripheral neuropathy (CIPN). However, the effect of therapies in cancer patients has yet to be investigated comprehensively. We hypothesized that cyclic thermal therapy would improve blood flow and microcirculation and improve the symptoms driven by CIPN. Methods: The criteria of assessment were blood volume in region of interest (ROI) in the images, and European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 questionnaire scores. The blood volume was quantified by using red blood cell (RBC) scintigraphy. All patients were treated 10 times during 10 days. The thermal stimulations, between 15° and 41°, were repeatedly delivered to the patient's hands. Results: The total score of the questionnaires, the score of questions related to the upper limbs, the score of questions closely related to the upper limbs, and the score excluding the upper limbs questions was decreased. The blood volume was decreased, and the variance of blood volume was decreased. During cooling stimulation, the blood volume was decreased, and its variance was decreased. During warming stimulation, the blood volume was decreased, and its variance was decreased. Conclusions: We suggest that cyclic thermal therapy is useful to alleviate CIPN symptoms by blood circulation improvement. RBC scintigraphy can provide the quantitative information on blood volume under certain conditions such as stress, as well as rest, in peripheral tissue.

• Korean Journal of Radiology
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• v.22 no.3
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• pp.384-394
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• 2021

Objective: To quantitatively assess biochemical alterations in the cartilage of the subtalar and midtarsal joints in chronic lateral ankle instability (CLAI) patients with isolated anterior talofibular ligament (ATFL) injuries and combined calcaneofibular ligament (CFL) injuries using MRI T2 mapping. Materials and Methods: This study was performed according to regulations of the Committee for Human Research at our institution, and written informed consent was obtained from all participants. Forty CLAI patients (26 with isolated ATFL injuries and 14 with combined ATFL and CFL injuries) and 25 healthy subjects were recruited for this study. All participants underwent MRI scans with T2 mapping. Patients were assessed with the American Orthopedic Foot and Ankle Society (AOFAS) rating system. The subtalar and midtarsal joints were segmented into 14 cartilage subregions. The T2 value of each subregion was measured from T2 mapping images. Data were analyzed with ANOVA, the Student's t test, and Pearson's correlation coefficient. Results: T2 values of most subregions of the subtalar joint and the calcaneal facet of the calcaneocuboid joint in CLAI patients with combined CFL injuries were higher than those in healthy controls (all p < 0.05). However, there were no significant differences in T2 values in subtalar and midtarsal joints between patients with isolated ATFL injuries and healthy controls (all p > 0.05). Moreover, T2 values of the medial talar subregions of the posterior subtalar joint in patients with combined CFL injuries showed negative correlations with the AOFAS scores (r = -0.687, p = 0.007; r = -0.609, p = 0.021, respectively). Conclusion: CLAI with combined CFL injuries can lead to cartilage degeneration in subtalar and calcaneocuboid joints, while an isolated ATFL injury might not have a significant impact on the cartilage in these joints.

• Biomedical Science Letters
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• v.11 no.1
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• pp.23-29
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• 2005

Molecular imaging with targeted contrast agents enables tissues to be distinguished by detecting specific cell-surface receptors. In the present study, a ligand-targeted acoustic nanoparticle system is used to identify angioplasty-induced expression of tissue factor by smooth muscle cell within carotid arteries. Pig carotid arteries were overstretched with balloon catheters, treated with tissue factor-targeted or a control nanoparticle system, and imaged with intravascular ultrasound before and after treatment. Tissue factor-targeted emulsion bound and increased the echogenicity and gray-scale levels of overstretched smooth muscle cell within the tunica media, versus no change in contralateral control arteries. Expression of stretch-induced tissue factor in carotid artery media was confirmed by immunohistochemistry. The potential for abnormal thrombogenicity of balloon-injured arteries, as reflected by smooth muscle expression of tissue factor, was imaged using a novel, targeted, nanoparticulate ultrasonic contrast agent.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.1
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• pp.25-32
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• 2022

Malignant melanoma has an aggressive nature and high metastatic potential that result in one of the highest cancer mortality rates. Over the past three decades, primary and metastatic melanoma incidence has rapidly increased. The recent advances in diagnostic technology have shown promise, but there is still an enormous need for specific detection methods to diagnose malignant melanoma. Positron emission tomography can visualize a particular biomarker of malignant melanoma and promise a noninvasive image of micrometastases. However, the development of PET radiopharmaceuticals remains necessary for diagnosing malignant melanoma by using positron emission tomography. In this review, the history and a general overview of PET radionuclide labeled benzamide derivatives, including their radiosynthesis, in vivo characterization, and evaluation, are provided as imaging agents for malignant melanoma.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.6
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• pp.425-434
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• 2008

Dopamine transporter imaging is useful in the diagnosis of Parkinson's disease and the most successful technique in the clinical use of neuroreceptor imaging. Recently, several radiopharmaceuticals including I-123 FP-CIT, Tc-99m TRODAT, and F-18 FP-CIT for dopamine transporter imaging have been approved for the routine clinical use in several European countries, Taiwan and Korea, respectively. This review summarized the practical issue for the routine clinical examination of dopamine transporter imaging.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.5
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• pp.487-494
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• 2009

Purpose: Small size of recombinant scFv antibody has many advantages such as rapid blood clearances and improved targeting antibodies to tumor region. On the other hand owing to small size, number of amino group is insufficient in conjugation with chelator and fluorescence labeling. This study is to introduce poly lysine tag to the C-terminal end of scFv lym-1 sequence for fluorescence chelator conjugation. Materials and Methods: Poly lysine scFv lym-1 gene, cloned into pET-22b (+) vector, was expressed in E. coli BL21 (DE3) strain. Antibody purification was performed with Ni-NTA column and then size exclusion column chromatography. Expression and purification levels of poly lysine tagged scFv lym-1 antibody were confirmed by western blot analysis. I-124, I-125, I-131 and Tc-99m were used for radiolabeling of purified poly lysine scFv lym-1. Flow cytometry analysis of FIT( conjugated poly lysine scFv lym-1 was performed for confirmation of immunoreactivity of human Burkitt's lymphoma cells. Results: Poly lysine scFv lym-1 antibody was purified through two steps and identified as molecular weight of 48 KDa. Radiolabeling yields of I-124, I-125, I-131 and Tc-99m into poly lysine scFv lym-1 were >99%, >99%, >95% and >99%, respectively. Flow cytometry analysis of poly lysine scFv and scFv lym-1 was showed similar immunoreactivity to human Burkitt's lymphoma cells. Conclusion: Poly lysine tag was useful for the sufficient number of amino groups to scFv lym-1 antibody for chelator conjugation with minimizing loss of immunoreactivity.

• Molecules and Cells
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• v.41 no.7
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• pp.676-683
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• 2018

Cilia are highly specialized antennae-like organelles that extend from the cell surface and act as cell signaling hubs. Intraflagellar transport (IFT) is a specialized form of intracellular protein trafficking that is required for the assembly and maintenance of cilia. Because cilia are so important, mutations in several IFT components lead to human disease. Thus, clarifying the molecular functions of the IFT proteins is a high priority in cilia biology. Live imaging in various species and cellular preparations has proven to be an important technique in both the discovery of IFT and the mechanisms by which it functions. Live imaging of Drosophila cilia, however, has not yet been reported. Here, we have visualized the movement of IFT in Drosophila cilia using time-lapse live imaging for the first time. We found that NOMPB-GFP (IFT88) moves according to distinct parameters depending on the ciliary segment. NOMPB-GFP moves at a similar speed in proximal and distal cilia toward the tip (${\sim}0.45{\mu}m/s$). As it returns to the ciliary base, however, NOMPB-GFP moves at ${\sim}0.12{\mu}m/s$ in distal cilia, accelerating to ${\sim}0.70{\mu}m/s$ in proximal cilia. Furthermore, while live imaging NOMPB-GFP, we observed one of the IFT proteins required for retrograde movement, Oseg4 (WDR35), is also required for anterograde movement in distal cilia. We anticipate our time-lapse live imaging analysis technique in Drosophila cilia will be a good starting point for a more sophisticated analysis of IFT and its molecular mechanisms.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.1
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• pp.61-68
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• 2019

Purine type compounds has been recently reported to cause the death for lung cancer cell, related to microtubules-targeting agents (MTAs). Therefore it can be used to develop as theranostic radiopharmceuticals in nuclear medicine or gadolinium-based MRI imaging agents by chelate chemistry. In the study, we tried to chemically bind a DOTA chelate on the end of purine compound and obtained a specific conjugate of DOTA-purine for metal coordination. In particular, radiometal like Cu-64, for the development of MRI imaging agents, can be utilized to choice good candidates before the synthesis of gadolinium complexes. By the screening of radioisotope technique, Gd-DOTA-purine type complex was successfully prepared and showed MRI imaging for lung cancer cell into the mouse model.

• Progress in Medical Physics
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• v.21 no.2
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• pp.145-152
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• 2010

Inveon PET is a recently developed preclinical PET system for small animal. This study was conducted to measure the performance of Inveon PET as recommended by the NEMA NU 4-2008. We measured the spatial resolution, the sensitivity, the scatter fraction and the NECR using a F-18 source. A 3.432 ns coincidence window was used. A $1\;mm^3$ sized F-18 point source was used for the measurement of spatial resolution within an energy window of 350~625 keV. PET acquisition was performed to obtain the spatial resolution from the center to the 5 cm offset toward the edge of the transverse FOV. Sensitivity, scatter fraction, and NECR were measured within an energy window of 350~750 keV. For measuring the sensitivity, a F-18 line source (length: 12.7 cm) was used with concentric 5 aluminum tubes. For the acquisition of the scatter fraction and the NECR, two NEMA scatter phantoms (rat: 50 mm in diameter, 150 mm in length; mouse: 25 mm in diameter, 70 mm in length) were used and the data for 14 half-lives (25.6 hr) was obtained using the F-18 line source (rat: 316 MBq, mouse: 206 MBq). The spatial resolution of the F-18 point source was 1.53, 1.50 and 2.33 mm in the radial, tangential and axial directions, respectively. The volumetric resolution was $5.43\;mm^3$ in the center. The absolute sensitivity was 6.61%. The peak NECR was 486 kcps @121 MBq (rat phantom), and 1056 kcps @128 MBq (mouse phantom). The values of the scatter fraction were 20.59% and 7.93% in the rat and mouse phantoms, respectively. The performances of the Inveon animal PET scanner were measured in this study. This scanner will be useful for animal imaging.