• 대한방사성의약품학회지
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• 제8권1호
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• pp.3-8
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• 2022

Alteration of the mGluR5 density is closely related to various brain diseases including schizophrenia, depression, Parkinson's disease, and Alzheimer's disease. Therefore, mGluR5 is considered as a valuable imaging biomarker for brain disease and many radiopharmaceuticals have been developed so far. Among them, [¹⁸F]FPEB has favorable pharmacokinetic characteristics, and this is the most frequently used radiopharmaceutical for preclinical and clinical studies. In the present study, we want to introduce the optimized radiosynthetic method for the routine production of [¹⁸F]FPEB using a GE TRACERlabTM FXFN pro module. In addition, the entire process was monitored with a webcam to solve the problems arising from the synthetic process. As a result, [¹⁸F]FPEB was prepared by nucleophilic substitution from its nitro- precursor at 120℃ for 20 min in dimethyl sulfoxide. Radiochemical yield was 13.7 ± 5.1% (decay-corrected, n = 91) with the molar activity of 84 ± 17 GBq/µmol at the end of synthesis. The radiochemical purity was determined to be above 96%. The manufactured [¹⁸F]FPEB injection for quality controls were carried out in accordance with an KIRAMS approved protocol, as per ICH and USP guidelines.

• Journal of Korean Neurosurgical Society
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• 제57권6호
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• pp.415-421
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• 2015

Moyamoya disease (MMD) is an arteriopathy of the intracranial circulation predominantly affecting the branches of the internal carotid arteries. Heterogeneity in presentation, progression and response to therapy has prompted intense study to improve the diagnosis and prognosis of this disease. Recent progress in the development of moyamoya-related biomarkers has stimulated marked interest in this field. Biomarkers can be defined as biologically derived agents-such as specific molecules or unique patterns on imaging-that can identify the presence of disease or help to predict its course. This article reviews the current categories of biomarkers relevant to MMD-including proteins, cells and genes-along with potential limitations and applications for their use.

• 대한방사성의약품학회지
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• 제6권2호
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• pp.139-145
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• 2020

Polo-like kinase 1 (Plk1) is a key protein in mitosis and has been validated as a target for tumor therapy. It is well known to highly overexpress in many kinds of tumor, which has been implicated as a potential biomarker for tumor treatment and diagnosis. Plk1 consists of two domains, the N-terminus kinase domain and the C-terminus polo-box domain (PBD). The inhibitors have been developed for PBD of Plk1, which were shown a high level of affinity and selectivity for Plk1 that led to mitotic arrest and apoptotic cell death. This review discusses the inhibitors for PBD of Plk1 that are suitable for in vivo tumor treatment. They can be further extended for developing in vivo imaging probes for early diagnosis of tumor.

• Investigative Magnetic Resonance Imaging
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• 제21권3호
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• pp.125-130
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• 2017

Purpose: To evaluate the clinical significance of T1 high signal intensity on the globus pallidus as a predictor of severe hepatic encephalopathy in patients with acute-on-chronic liver failure (ACLF), which is a distinct syndrome characterized by multi-organ dysfunction including cerebral failure. Materials and Methods: From January 2002 to April 2014, we retrospectively reviewed the magnetic resonance imaging (MRI) findings and clinical and magnetic resonance (MR) features of 74 consecutive patients (44 men and 30 women; mean age, 59.5 years) with liver cirrhosis. The chronic liver failure-sequential organ failure assessment score was used to diagnose ACLF. The pallidal index (PI), calculated by dividing the mean signal intensity of the globus pallidus by that of the subcortical frontal white matter were compared according to ACLF. The PI was compared with the Model for End-Stage Liver Disease (MELD) score in predicting the development of ACLF. Results: Fifteen patients who were diagnosed with ACLF had higher hepatic encephalopathy grades (initial, P = 0.024; follow-up, P = 0.002), MELD scores (P < 0.001), and PI (P = 0.048). In the ACLF group, the mean PI in patients with cerebral failure was significantly higher than that in the patients without cerebral failure (1.33 vs. 1.20, P = 0.039). In patients with ACLF, the area under the curve (AUC) for PI was 0.680 (95% confidence intervals [CI], 0.52-0.85), which was significantly lower than that for the MELD score (AUC, 0.88; 95% CI, 0.77-0.99) (P = 0.04). Conclusion: The PI can be an ancillary biomarker for predicting the development of ACLF and severe hepatic encephalopathy.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권6호
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• pp.555-563
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• 2021

Purpose: The aim of this study was to evaluate the pancreatic fat fraction (PFF) using magnetic resonance imaging (MRI) in children with and without obesity and to correlate PFF with body mass index (BMI) z-score, hepatic fat fraction (HFF), and ultrasonography-derived pancreato-perihepatic fat index (PPHFI). Methods: This prospective study included 45 children with obesity and 19 without obesity (control group). PFF and HFF were quantitatively assessed using the abdominal multi-echo Dixon method for MRI. The PPHFI was assessed using transabdominal ultrasonography. Anthropometric, MRI, and ultrasonographic characteristics were compared between the two groups. Correlations between PFF, HFF, PPHFI, and BMI z-scores in each group were also analyzed. Results: The PFF, HFF, PPHFI, and BMI z-score were higher in the group with obesity than in the control group (PFF: 6.65±3.42 vs. 1.78±0.55, HFF: 19.5±13.0 vs. 2.31±1, PPHFI: 3.65 ±1.63 vs. 0.94±0.31, BMI z-score: 2.27±0.56 vs. 0.42±0.54, p<0.01, respectively). PFF was correlated with BMI z-scores, PPHFI, and HFF in the obesity group, and multivariate analysis showed that PFF was strongly correlated with BMI z-score and PPHFI (p<0.05). The BMI z-score was strongly correlated with PFF in the control group (p<0.01). Conclusion: These results suggest that MRI-derived PFF measures are associated with childhood obesity. PFF and PPHFI were also highly correlated in the obesity group. Therefore, PFF may be an objective index of pancreatic fat content and has the potential for clinical utility as a non-invasive biomarker for the assessment of childhood obesity.

• Korean Journal of Radiology
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• 제20권5호
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• pp.801-811
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• 2019

Objective: To determine whether diffusion kurtosis imaging (DKI) is effective in monitoring tumor response to neoadjuvant chemotherapy in patients with osteosarcoma. Materials and Methods: Twenty-nine osteosarcoma patients (20 men and 9 women; mean age, 17.6 ± 7.8 years) who had undergone magnetic resonance imaging (MRI) and DKI before and after neoadjuvant chemotherapy were included. Tumor volume, apparent diffusion coefficient (ADC), mean diffusivity (MD), mean kurtosis (MK), and change ratio (ΔX) between pre-and post-treatment were calculated. Based on histologic response, the patients were divided into those with good response (≥ 90% necrosis, n = 12) and those with poor response (< 90% necrosis, n = 17). Several MRI parameters between the groups were compared using Student's t test. The correlation between image indexes and tumor necrosis was determined using Pearson's correlation, and diagnostic performance was compared using receiver operating characteristic curves. Results: In good responders, MD_post, ADC_post, and MK_post values were significantly higher than in poor responders (p < 0.001, p < 0.001, and p = 0.042, respectively). The ΔMD and ΔADC were also significantly higher in good responders than in poor responders (p < 0.001 and p = 0.01, respectively). However, no significant difference was observed in ΔMK (p = 0.092). MD_post and ΔMD showed high correlations with tumor necrosis rate (r = 0.669 and r = 0.622, respectively), and MD_post had higher diagnostic performance than ADC_post (p = 0.037) and MK_post (p = 0.011). Similarly, ΔMD also showed higher diagnostic performance than ΔADC (p = 0.033) and ΔMK (p = 0.037). Conclusion: MD is a promising biomarker for monitoring tumor response to preoperative chemotherapy in patients with osteosarcoma.

• 대한치매학회지
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• 제23권2호
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• pp.95-106
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• 2024

Background and Purpose: Ventricle enlargement has been implicated in the pathophysiology of Alzheimer's disease (AD). We studied the relationship between ventricular size and cognitive function in patients with AD. We focused on the effect of the initial ventricle size on the rate of cognitive decline in patients with AD. Methods: A retrospective analysis of probable clinical AD participants with more than 2 magnetic resonance imaging images was performed. To measure ventricle size, we used visual rating scales of (1) Cardiovascular Health Study (CHS) score and (2) conventional linear measurement method. Results: Increased clinical dementia rating (CDR) was correlated with a decreased Mini-Mental Status Examination (MMSE) score, and increased medial temporal lobe atrophy (MTLA) and global ventricle size (p<0.001, p<0.001, p=0.021, respectively). There was a significant correlation between the change in cognitive function in the group (70%-100%ile) with a large initial ventricle size (p=0.021 for ∆CDR, p=0.01 for ∆MMSE), while the median ventricle size (30%-70%ile) showed correlation with other brain structural changes (MTLA, frontal atrophy [FA], and white matter) (p=0.036 for initial MTLA, p=0.034 for FA). Conclusions: In this study, the initial ventricle size may be a potential new imaging biomarker for initial cognitive function and clinical progression in AD. We found a relationship between the initial ventricle size and initial AD-related brain structural biomarkers.

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.113-125
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• 2018

Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells. Theragnosis is a concept in next-generation medicine that simultaneously combines accurate diagnostics with therapeutic effects. Molecular components in exosomes have been found to be related to certain diseases and treatment responses, indicating that they may have applications in diagnosis via molecular imaging and biomarker detection. In addition, recent studies have reported that exosomes have immunotherapeutic applications or can act as a drug delivery system for targeted therapies with drugs and biomolecules. In this review, we describe the formation, structure, and physiological roles of exosomes. We also discuss their roles in the pathogenesis and progression of diseases including neurodegenerative diseases, cardiovascular diseases, and cancer. The potential applications of exosomes for theragnostic purposes in various diseases are also discussed. This review summarizes the current knowledge about the physiological and pathological roles of exosomes as well as their diagnostic and therapeutic uses, including emerging exosome-based therapies that could not be applied until now.

• Korean Journal of Radiology
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• 제23권4호
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• pp.446-454
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• 2022

Objective: To evaluate whether hyperoxia-induced ΔR₁ (hyperO₂ΔR₁) can accurately identify histological infarction in an acute cerebral stroke model. Materials and Methods: In 18 rats, MRI parameters, including hyperO₂ΔR₁, apparent diffusion coefficient (ADC), cerebral blood flow and volume, and ¹⁸F-fluorodeoxyglucose uptake on PET were measured 2.5, 4.5, and 6.5 hours after a 60-minutes occlusion of the right middle cerebral artery. Histological examination of the brain was performed immediately following the imaging studies. MRI and PET images were co-registered with digitized histological images. The ipsilateral hemisphere was divided into histological infarct (histological cell death), non-infarct ischemic (no cell death but ADC decrease), and nonischemic (no cell death or ADC decrease) areas for comparisons of imaging parameters. The levels of hyperO₂ΔR₁ and ADC were measured voxel-wise from the infarct core to the non-ischemic region. The correlation between areas of hyperO₂ΔR₁-derived infarction and histological cell death was evaluated. Results: HyperO₂ΔR₁ increased only in the infarct area (p ≤ 0.046) compared to the other areas. ADC decreased stepwise from non-ischemic to infarct areas (p = 0.002 at all time points). The other parameters did not show consistent differences among the three areas across the three time points. HyperO₂ΔR₁ sharply declined from the core to the border of the infarct areas, whereas there was no change within the non-infarct areas. A hyperO₂ΔR₁ value of 0.04 s^-1 was considered the criterion to identify histological infarction. ADC increased gradually from the infarct core to the periphery, without a pronounced difference at the border between the infarct and non-infarct areas. Areas of hyperO₂ΔR₁ higher than 0.04 s^-1 on MRI were strongly positively correlated with histological cell death (r = 0.862; p < 0.001). Conclusion: HyperO₂ΔR₁ may be used as an accurate and early (2.5 hours after onset) indicator of histological infarction in acute stroke.

• Molecules and Cells
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• 제38권7호
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• pp.624-629
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• 2015

Since the emergence of proteomics methods, many proteins specific for renal cell carcinoma (RCC) have been identified. Despite their usefulness for the specific diagnosis of RCC, such proteins do not provide spatial information on the diseased tissue. Therefore, the identification of cancer-specific proteins that include information on their specific location is needed. Recently, matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) based imaging mass spectrometry (IMS) has emerged as a new tool for the analysis of spatial distribution as well as identification of either proteins or small molecules in tissues. In this report, surgical tissue sections of papillary RCC were analyzed using MALDI-IMS. Statistical analysis revealed several discriminative cancer-specific m/z-species between normal and diseased tissues. Among these m/z-species, two particular proteins, S100A11 and ferritin light chain, which are specific for papillary RCC cancer regions, were successfully identified using LC-MS/MS following protein extraction from independent RCC samples. The expressions of S100A11 and ferritin light chain were further validated by immunohistochemistry of human tissues and tissue microarrays (TMAs) of RCC. In conclusion, MALDI-IMS followed by LC-MS/MS analysis in human tissue identified that S100A11 and ferritin light chain are differentially expressed proteins in papillary RCC cancer regions.