• Journal of Radiopharmaceuticals and Molecular Probes
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• v.6 no.1
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• pp.27-38
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• 2020

Alzheimer's disease (AD) is one of the challenging conditions that have no cure, yet early diagnosis can help to control the disease. PET imaging of tau has several advantages, such as being a noninvasive, safe diagnostic technique that correlates directly with the disease progression. Many tau tracers have been reported to date; however, the chemical scaffolds of them fall in a narrow chemical window, and none was approved yet as none is entirely selective and sensitive to tau. These problems are being solved as new tracers emerge constantly. In this report, the first-generation tau tracers such as [¹¹C]PBB3, 2-arylquinoline (THK) series, [¹⁸F]T808, and [¹⁸F]AV-1451 ([¹⁸F]T807) are reviewed from an organic and radiochemistry perspective; thus the most effective chemical approach to synthesize these tracers is discussed. This would help to design novel tracers which can meet the challenges faced by the current tracers.

• Journal of the Korean Society of Radiology
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• v.83 no.3
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• pp.453-472
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• 2022

Over the past decades, the immense clinical need for early detection methods and treatments for dementia has become a priority worldwide. The advances in PET biomarkers play increasingly important roles in understanding disease mechanisms by demonstrating the protein pathology underlying dementia in the brain. Amyloid-β and tau deposition in PET images are now key diagnostic biomarkers for the Alzheimer's disease continuum. The inclusion of biomarkers in the diagnostic criteria has achieved a paradigm shift in facilitating early differential diagnosis, predicting disease prognosis, and influencing clinical management. Furthermore, in vivo images showing pathology could become prognostic as well as surrogate biomarkers in therapeutic trials. In this review, we focus on recent developments in radiotracers for amyloid-β and tau PET imaging in Alzheimer's disease and other neurodegenerative diseases. Further, we introduce their potential application as future perspectives.

• Dementia and Neurocognitive Disorders
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• v.17 no.3
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• pp.110-119
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• 2018

Background and Purpose: To analyze $^{18}F-THK5351$ positron emission tomography (PET) scans of patients with clinically diagnosed nonfluent/agrammatic variant primary progressive aphasia (navPPA). Methods: Thirty-one participants, including those with Alzheimer's disease (AD, n=13), navPPA (n=3), and those with normal control (NC, n=15) who completed 3 Tesla magnetic resonance imaging, $^{18}F-THK5351$ PET scans, and detailed neuropsychological tests, were included. Voxel-based and region of interest (ROI)-based analyses were performed to evaluate retention of $^{18}F-THK5351$ in navPPA patients. Results: In ROI-based analysis, patients with navPPA had higher levels of THK retention in the Broca's area, bilateral inferior frontal lobes, bilateral precentral gyri, and bilateral basal ganglia. Patients with navPPA showed higher levels of THK retention in bilateral frontal lobes (mainly left side) compared than NC in voxel-wise analysis. Conclusions: In our study, THK retention in navPPA patients was mainly distributed at the frontal region which was well correlated with functional-radiological distribution of navPPA. Our results suggest that tau PET imaging could be a supportive tool for diagnosis of navPPA in combination with a clinical history.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.3 no.2
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• pp.91-97
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• 2017

$^{18}F-THK-5351$ is a PET radiotracer to image the hyperphosphorylated tau fibrillar aggregates in human brain. This protocol describes the optimized radiosynthesis of $^{18}F-THK-5351$ using a commercial GE $TRACERlab^{TM}$ $FX_{FN}$ radiosynthesis module. $^{18}F-THK-5351$ was prepared by nucleophilic [$^{18}F$]fluorination from its protected tosylate precursors, (S)-(2-(2-methylaminopyrid-5-yl)-6-[[2-(tetrahydro-2H-pyran-2-yloxy)-3-tosyloxy]propoxy] quinolone(THK-5352), at $110^{\circ}C$ for 10 min in dimethyl sulfoxide, followed by deprotection with 1 N HCl. The average radiochemical yield of $^{18}F-THK-5351$ was $31.9{\pm}6.7%$(decay-corrected, n = 10), with molar activity of $198.1{\pm}33.9GBq/{\mu}mol$($5.4{\pm}0.9Ci/{\mu}mol$, n = 10). The radiochemical purity was determined to be above 98%. The overall production time including HPLC purification is approximately 70 min. This fully-automated protocol is validated for clinical use.

• Korean Journal of Remote Sensing
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• v.30 no.4
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• pp.525-536
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• 2014

In this study, a method to assess and monitor hydrological drought using remote sensing was investigated for use in regions with limited observation data, and was applied to the Upper Namhangang basin in South Korea, which was seriously affected by the 2008-2009 drought. Drought information may be obtained more easily from meteorological data based on water balance than hydrological data that are hard to estimate. Air temperature data at 2 m above ground level (AGL) were estimated using remotely sensed data, evapotranspiration was estimated from the air temperature, and the correlations between precipitation minus evapotranspiration (P-PET) and streamflow percentiles were examined. Land Surface Temperature data with $1{\times}1km$ spatial resolution as well as Atmospheric Profile data with $5{\times}5km$ spatial resolution from MODIS sensor on board Aqua satellite were used to estimate monthly maximum and minimum air temperature in South Korea. Evapotranspiration was estimated from the maximum and minimum air temperature using the Hargreaves method and the estimates were compared to existing data of the University of Montana based on Penman-Monteith method showing smaller coefficient of determination values but smaller error values. Precipitation was obtained from TRMM monthly rainfall data, and the correlations of 1-, 3-, 6-, and 12-month P-PET percentiles with streamflow percentiles were analyzed for the Upper Namhan-gang basin in South Korea. The 1-month P-PET percentile during JJA (r = 0.89, tau = 0.71) and SON (r = 0.63, tau = 0.47) in the Upper Namhan-gang basin are highly correlated with the streamflow percentile with 95% confidence level. Since the effect of precipitation in the basin is especially high, the correlation between evapotranspiration percentile and streamflow percentile is positive. These results indicate that remote sensing-based P-PET estimates can be used for the assessment and monitoring of hydrological drought. The high spatial resolution estimates can be used in the decision-making process to minimize the adverse impacts of hydrological drought and to establish differentiated measures coping with drought.

• Dementia and Neurocognitive Disorders
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• v.17 no.4
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• pp.163-173
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• 2018

Background and Purpose: Behavioral variant frontotemporal dementia (bvFTD) is a subtype of frontotemporal dementia, which has clinical symptoms of progressive personality and behavioral changes with deterioration of social cognition and executive functions. The pathology of bvFTD is known to be tauopathy or TDP-43 equally. We analyzed the $^{18}F-THK5351$ positron emission tomography (PET) scans, which were recently developed tau PET, in patients with clinically-diagnosed bvFTD. Methods: Forty-eight participants, including participants with behavioral variant frontotemporal dementia (bvFTD, n=3), Alzheimer's disease (AD, n=21) and normal cognition (NC, n=24) who completed 3T magnetic resonance images, $^{18}F-THK5351$ PET scans, and detailed neuropsychological tests were included in the study. Voxel-wise statistical analysis and region of interest (ROI)-based analyses were performed to evaluate the retention of THK in bvFTD patients. Results: In the voxel-based and ROI-based analyses, patients with bvFTD showed greater THK retention in the prefrontal, medial frontal, orbitofrontal, anterior cingulate, insula, anterior inferior temporal and striatum regions compared to NC participants. Left-right asymmetry was noted in the bvFTD patients. A patient with extrapyramidal symptoms showed much greater THK retention in the brainstem. Conclusions: The distribution of THK retention in the bvFTD patients was mainly in the frontal, insula, anterior temporal, and striatum regions which are known to be the brain regions corresponding to the clinical symptoms of bvFTD. Our study suggests that $^{18}F-THK5351$ PET imaging could be a supportive tool for diagnosis of bvFTD.

• The Korean Journal of Nuclear Medicine Technology
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• v.22 no.1
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• pp.51-54
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• 2018

Purpose $^{18}F-THK5351$ is the newly developed PET probe for tau imaging in alzheimer's disease. The purpose of study was to establish the automated production of $^{18}F-THK5351$ on a commercial module. Materials and Methods Two different approaches were evaluated for the synthesis of $^{18}F-THK5351$. The first approach (method I) included the nucleophilic $^{18}F$-fluorination of the tosylate precursor, subsequently followed by pre-HPLC purification of crude reaction mixture with SPE cartridge. In the second approach (method II), the crude reaction mixture was directly introduced to a semi-preparative HPLC without SPE purification. The radiosynthesis of $^{18}F-THK5351$ was performed on a commercial GE $TRACERlab^{TM}$ $FX-_{FN}$ module. Quality control of $^{18}F-THK5351$ was carried out to meet the criteria guidelined in USP for PET radiopharmaceuticals. Results The overall radiochemical yield of method I was $23.8{\pm}1.9%$ (n=4) as the decay-corrected yield (end of synthesis, EOS) and the total synthesis time was $75{\pm}3min$. The radiochemical yield of method II was $31.9{\pm}6.7%$ (decay-corrected, n=10) and the total preparation time was $70{\pm}2min$. The radiochemical purity was>98%. Conclusion This study shows that method II provides higher radiochemical yield and shorter production time compared to the pre-SPE purification described in method I. The $^{18}F-THK5351$ synthesis by method II will be ideal for routine clinical application, considering short physical half-life of fluorine-18 ($t_{1/2}=110min$).

• Textile Coloration and Finishing
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• v.13 no.6
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• pp.33-33
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• 2001

The physical properties and the dyeability of the easily dyeable polyester yarn(EDY) were investigated and compared with those of regular polyester (REG-PET). The EDY, copolymerized with small amount of polyethylene glycol(PEG), showed higher intensity of aliphatic CH peak in IR spectrum, lower density and lower compactness than those of the REG-PET from the analysis of IR, density gradient column and XRD respectively. In the physical properties, the EDY has lowers $T_g,\;T_m$, specific stress and initial modulus, and also has higher strain than that of the REG-PET. The EDY can be dyed under atmospheric pressure and its dyeing rate was faster than REG-PET due to low $T_d$, and this seems to be caused by the increased flexibility of Polymer chain in amorphous region of the EDY due to the copolymerization of PEG.ns being within the experimental error, the average values of lifetim.
$\tau$(t) are taken for further calculations. Rate constants such as Stern-Volmer quenching constants K$_{sv}$, quenching rate parameters k$_q$ and k''$_q$, static quenching constant V and kinetic distance r are determined using the modified Stern-Volmer eq.
tion and sphere of action static quenching model. In order to see whether the reactions are diffusion limited, equations k$_q$ = e$^{-Eq/RT}$ and k''$_q$ = e$^{-Eq/RT}$ are used to determine the values of E$_q$ and E''$_q$, the activati.
energies for collisional quenching and the values of E$_q$ are 14.53, 17.28 and 16.20 kJ mole$^{-1}$ for MPNO1, MPNO2 and 2-PI respectively and the values of E''$_q$ are 14.62 and 17.73 for MPNO1 and MPNO2 respectively. From the magnitudes of various quantities it has.
een concluded that the reactions are diffusion limited and the observed positive deviations in the S-V plot are due to static and dynamic quenching.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.6 no.2
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• pp.61-68
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• 2020

Aggregated neurofibrillary tangles (NFTs) are a pathological hallmark in Alzheimer's disease (AD) and many radiopharmaceuticals targeting NFTs have been developed so far. Among these, [¹⁸F]flortaucipir (TAUVID^TM) is the first approved radiopharmaceutical in the Food and Drug Administration (FDA) to image tau pathology. In the present study, we describe the optimized radiosynthetic method for the routine production of [¹⁸F] flortaucipir using a commercialized automation module (i.e. GE TRACERlab^TM FX_FN pro). [¹⁸F]Flortaucipir was prepared by nucleophilic substitution from its N-tert-butoxycarbonyl protected nitro precursor, tertbutyl 7-(6-nitropyridin-3-yl)-5H-pyrido[4,3-b]indole-5-carboxylate, at 130℃ for 10 min in dimethyl sulfoxide. The mean radiochemical yield was 20 ± 4.3% (decay-corrected, n = 47) with the molar activity of 218 ± 32 GBq/µmol at the end of synthesis. The radiochemical purity was determined to be above 95%. The overall production time including quality control is approximately 100min. The final produced [¹⁸F]flortaucipir injection meets the USP criteria for quality control. Thus, this fully automated system is validated for clinical use.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.1
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• pp.30-41
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• 2007

Purpose: Bone metastasis in breast cancer patients are usually assessed by conventional Tc-99m methylene diphosphonate whole-body bone scan, which has a high sensitivity but a poor specificity. However, positron emission tomography with $^{18}F-2-deoxyglucose$ (FDG-PET) can offer superior spatial resolution and improved specificity. FDG-PET/CT can offer more information to assess bone metastasis than PET alone, by giving a anatomical information of non-enhanced CT image. We attempted to evaluate the usefulness of FDG-PET/CT for detecting bone metastasis in breast cancer and to compare FDG-PET/CT results with bone scan findings. Materials and Methods: The study group comprised 157 women patients (range: $28{\sim}78$ years old, $mean{\pm}SD=49.5{\pm}8.5$) with biopsy-proven breast cancer who underwent bone scan and FDG-PET/CT within 1 week interval. The final diagnosis of bone metastasis was established by histopathological findings, radiological correlation, or clinical follow-up. Bone scan was acquired over 4 hours after administration of 740 MBq Tc-99m MDP. Bone scan image was interpreted as normal, low, intermediate or high probability for osseous metastasis. FDG PET/CT was performed after 6 hours fasting. 370 MBq F-18 FDG was administered intravenously 1 hour before imaging. PET data was obtained by 3D mode and CT data, used as transmission correction database, was acquired during shallow respiration. PET images were evaluated by visual interpretation, and quantification of FDG accumulation in bone lesion was performed by maximal SUV(SUVmax) and relative SUV(SUVrel). Results: Six patients(4.4%) showed metastatic bone lesions. Four(66.6%) of 6 patients with osseous metastasis was detected by bone scan and all 6 patients(100%) were detected by PET/CT. A total of 135 bone lesions found on either FDG-PET or bone scan were consist of 108 osseous metastatic lesion and 27 benign bone lesions. Osseous metastatic lesion had higher SUVmax and SUVrel compared to benign bone lesion($4.79{\pm}3.32$ vs $1.45{\pm}0.44$, p=0.000, $3.08{\pm}2.85$ vs $0.30{\pm}0.43$, p=0.000). Among 108 osseous metastatic lesions, 76 lesions showed as abnormal uptake on bone scan, and 76 lesions also showed as increased FDG uptake on PET/CT scan. There was good agreement between FDG uptake and abnormal bone scan finding (Kendall tau-b : 0.689, p=0.000). Lesion showed increased bone tracer uptake had higher SUVmax and SUVrel compared to lesion showed no abnormal bone scan finding ($6.03{\pm}3.12$ vs $1.09{\pm}1.49$, p=0.000, $4.76{\pm}3.31$ vs $1.29{\pm}0.92$, p=0.000). The order of frequency of osseous metastatic site was vertebra, pelvis, rib, skull, sternum, scapula, femur, clavicle, and humerus. Metastatic lesion on skull had highest SUVmax and metastatic lesion on rib had highest SUVrel. Osteosclerotic metastatic lesion had lowest SUVmax and SUVrel. Conclusion: These results suggest that FDG-PET/CT is more sensitive to detect breast cancer patients with osseous metastasis. CT scan must be reviewed cautiously skeleton with bone window, because osteosclerotic metastatic lesion did not showed abnormal FDG accumulation frequently.