• Bulletin of the Korean Chemical Society
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• 제26권1호
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• pp.91-96
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• 2005

O-(3-[$^{18}$F]Fluoropropyl)-L-tyrosine (L-[$^{18}$F]FPT) was synthesized by nucleophilic radiofluorination followed by acidic hydrolysis of protective groups and evaluated with 9 L tumor bearing rat. L-[$^{18}$F]FPT is an homologue of O-(2-[$^{18}$F]fluoroethyl)-L-tyrosine (L-[$^{18}$F]FET) which recently is studied as a tracer for tumor imaging using positron emission tomography (PET). [$^{18}$F]FPT was directly prepared from the precursor of O-(3-ptoluenesulfonyloxypropyl)- N-(tert-butoxycarbonyl)-L-tyrosine methyl ester. FPT-PET image was obtained at 60 min in 9 L tumor bearing rats. The radiochemical yield of [$^{18}$F]FPT was 0-45% (decay corrected) and the radiochemical purity was more than 95% after HPLC purification. The total time elapsed for the synthesis of [$^{18}$F]FPT was 100 min from EOB (End-of-bombardment). A comparison of uptake studies between [$^{18}$F]FPT and [$^{18}$F]FET was performed. In biodistribution, [$^{18}$F]FPT showed similar pattern with [$^{18}$F]FET in various tissues, but [$^{18}$F]FPT showed low uptake in brain. Furthermore, [$^{18}$F]FPT showed higher tumor-to-brain ratio than [$^{18}$F]FET. In conclusion, [$^{18}$F]FPT seems to be more useful amino acid tracer than [$^{18}$F]FET for brain tumors imaging with PET.

• Journal of Korean Neurosurgical Society
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• 제54권6호
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• pp.467-476
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• 2013

Objective : This study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction. Methods : Male Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), $T2^*$ weighted image ($T2^*WI$), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining. Results : Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by $T2^*WI$ and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups. Conclusion : In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain.

• Investigative Magnetic Resonance Imaging
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• 제21권2호
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• pp.65-70
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• 2017

Purpose: To optimize the saturation time and maximizing the pH-weighted difference between the normal and ischemic brain regions, on 3-tesla amide proton transfer (APT) imaging using an in vivo rat model. Materials and Methods: Three male Wistar rats underwent middle cerebral artery occlusion, and were examined in a 3-tesla magnetic resonance imaging (MRI) scanner. APT imaging acquisition was performed with 3-dimensional turbo spin-echo imaging, using a 32-channel head coil and 2-channel parallel radiofrequency transmission. An off-resonance radiofrequency pulse was applied with a Sinc-Gauss pulse at a $B_{1,rms}$ amplitude of $1.2{\mu}T$ using a 2-channel parallel transmission. Saturation times of 3, 4, or 5 s were tested. The APT effect was quantified using the magnetization-transfer-ratio asymmetry at 3.5 ppm with respect to the water resonance (APT-weighted signal), and compared with the normal and ischemic regions. The result was then applied to an acute stroke patient to evaluate feasibility. Results: Visual detection of ischemic regions was achieved with the 3-, 4-, and 5-s protocols. Among the different saturation times at $1.2{\mu}T$ power, 4 s showed the maximum difference between the ischemic and normal regions (-0.95%, P = 0.029). The APTw signal difference for 3 and 5 s was -0.9% and -0.7%, respectively. The 4-s saturation time protocol also successfully depicted the pH-weighted differences in an acute stroke patient. Conclusion: For 3-tesla turbo spin-echo APT imaging, the maximal pH-weighted difference achieved when using the $1.2{\mu}T$ power, was with the 4 s saturation time. This protocol will be helpful to depict pH-weighted difference in stroke patients in clinical settings.

• Korean Journal of Radiology
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• 제19권6호
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• pp.1161-1171
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• 2018

Objective: The aim of this study was to investigate diffusion tensor (DT) imaging-derived properties of benign oligemia, true "at risk" penumbra (TP), and the infarct core (IC) during the first 3 hours of stroke onset. Materials and Methods: The study was approved by the local animal care and use committee. DT imaging data were obtained from 14 rats after permanent middle cerebral artery occlusion (pMCAO) using a 7T magnetic resonance scanner (Bruker) in room air. Relative cerebral blood flow and apparent diffusion coefficient (ADC) maps were generated to define oligemia, TP, IC, and normal tissue (NT) every 30 minutes up to 3 hours. Relative fractional anisotropy (rFA), pure anisotropy (rq), diffusion magnitude (rL), ADC (rADC), axial diffusivity (rAD), and radial diffusivity (rRD) values were derived by comparison with the contralateral normal brain. Results: The mean volume of oligemia was $24.7{\pm}14.1mm^3$, that of TP was $81.3{\pm}62.6mm^3$, and that of IC was $123.0{\pm}85.2mm^3$ at 30 minutes after pMCAO. rFA showed an initial paradoxical 10% increase in IC and TP, and declined afterward. The rq, rL, rADC, rAD, and rRD showed an initial discrepant decrease in IC (from -24% to -36%) as compared with TP (from -7% to -13%). Significant differences (p < 0.05) in metrics, except rFA, were found between tissue subtypes in the first 2.5 hours. The rq demonstrated the best overall performance in discriminating TP from IC (accuracy = 92.6%, area under curve = 0.93) and the optimal cutoff value was -33.90%. The metric values for oligemia and NT remained similar at all time points. Conclusion: Benign oligemia is small and remains microstructurally normal under pMCAO. TP and IC show a distinct evolution of DT-derived properties within the first 3 hours of stroke onset, and are thus potentially useful in predicting the fate of ischemic brain.

• Investigative Magnetic Resonance Imaging
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• 제3권2호
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• pp.167-172
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• 1999

목적 : Echo planar image (EPn와 다론 MR 영상기법에서 2시간 이내의 초급성 출혈의 발견율의 차이를 비교해 보고자 한다. 대상 및 방법 : 인위적으로 뇌출혈을 유발시킨 백서 10마리를 대상으로 EP1, 급속 스핀에코 (FSE) T2 강조영상, Fluid attenuated inversion recovery (FLAIR) 영상, 스펀에코 (SE) Tl 강조영상과 Tl 강조 Gradient echo (GE) 영상을 이용하여, 뇌출혈을 일으킨 2시간 후에 MR 촬영을 하였다. 추가적으로 3마리는 출혈 30분 후에, 6마리는 1시간 후에 각각 EPI와 FSE T2 강조영상을 얻었다. 얻어진 영상에 대한 주관적인 시각적 평가를 하기위하여 세명의 방사선과 의사가 출혈 병변이 어느 MR 영상 기법에서 제일 잘 보이는지를 평가하였다. 정량적인 평가 로는 병변-정상 뇌설질의 대조잡음비(contrast-to-noise ratio, CNR)를 측정하였다. 통계처리는 Wilcoxon-Ranks test를 이용하였다. 결과 : 시각적 평가에서 출혈 병변이 높은 신호강도로 나타난 EP1, FLAIR, FSE T2 영상 중 EPI 영상이 특히 높은 신호강도로 나타나 제일 쉽게 병변이 구별되었다. 정량적인 평가에서 출혈 병 변-정상 뇌설질의 CNR은 EPI와 FLAIR 영상에서 다른 세 영상기법에 비해 통계적으로 유의하게 우월하였다 (p<0.01). 그러나 EPI와 FLAIR 영상간의 CNR은 동계적으로 유의한 차이가 없었다 (p>0.10). 추가적으로 출혈 30분과 1l시간 후 촬영한 모두에서 EPI영상과 FSE T2 강조 영상은 정상에 비해 높은 신호강도를 보여 병변의 구별이 가능하였다. 결론 : 백서에서 유발시킨 초급성기 뇌출혈의 여러 기법의 MR 영상 중 EPI 영상이 영상획득 시간이 가장 빠르면서 시각적 평가와 정량적 평가에서 출혈의 발견율이 가장 높아 출혈의 선속한 진단에 유용할 것으로 생각된다.

• 대한핵의학회지
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• 제29권3호
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• pp.328-331
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• 1995

$^{99m}Tc$ labeled PnAO(propylene amine oxime) derivatives have been widely studied as brain perfusion agents. We synthesized and characterized a PnAO derivative, (RR/SS/ meso)-4,8-diaza-3,9-dimethylundecane-2, 10-dione bisoxime(PRODD). Proton-NMR spectroscopy and thin layer chromatography(silica gel) were performed for its characterization. PRODD was labeled with $^{99m}Tc$ using stannous chloride as reducing agent. The labeling efficiency was determined to be about 85%. Brain uptakes of $4.16{\pm}0.42$ %ID/g and $3.24{\pm}0.13$ %ID/g were found after 10min and 30min after intravenous injection. Brain-to-blood ratios were 1.17 and 0.75 at 10 and 30 minutes, which were lower than 1.3 and 1.9 of the ratios with commercial ${\pm}$-HMPAO. Autoradiographs of rat brain sections showed the gray matter to white matter ratios of $1.13{\pm}0.10$ at 30 min after intravenous injection, which was lower than $1.94{\pm}0.19$ of commercial $^{99m}Tc$-HMPAO. With the above findings, we concluded that the lipophilic $^{99m}Tc$-PRODD complex was able to cross the blood-brain barrier, however the complex showed lower uptake than $^{99m}Tc$-HMPAO in mouse or rat brains. We could suggest possibility that PRODD could be used as another $^{99m}Tc$ chelator.

• 대한의용생체공학회:의공학회지
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• 제43권4호
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• pp.193-198
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• 2022

Contrast enhanced magnetic resonance imaging using gadolinium-based contrast agent (GBCA) is a very useful in vivo technique to visualize the inner ear pathology including endolymphatic hydrops. Although systemic intravenous (IV) administration can visualize the perilymph space, the visualization was possible by indirect passage of contrast agent through blood-perilymph barrier. All animal experimental procedures were performed under anesthesia with 5% isoflurane. Lipopolysaccharide (LPS) was instilled into the left tympanic cavity through the tympanic membrane using a sterile 27gauge needle to induce hydrops model. Tucker-Davis Technologies system was used to measure Auditory Brainstem Responses (ABRs). For intracerebroven-tricular (ICV) administration, 25 µmol of GADOVIST (Bayer, Berlin, Germany) was used and diluted GADOVIST injection was 10 µl. MR imaging was acquired with a 9.4 Tesla MRI scanner. Transmit-receive volume coil with 40 mm inner diameter and 75 mm out diameter was used. ICV administration well demonstrated the strong enhancement along the cerebrospinal fluid (CSF) microcirculation pathway including CSF fluid in the subarachnoid space and CSF space of the inner ear structures. On the other hand, IV administration showed no contrast enhancement along the CSF microcirculation pathway and showed weak enhancement in the inner ear structures. In case of rat hydrops model, ICV administration showed that the reduced contrast enhancement in the perilymph space of the hydrops induced inner ear compared to the contrast enhancement in the perilymph space of the normal inner ear. New systemic ICV administration method provide contrast enhancement of GBCA in the inner ear through CSF microcirculation pathway.

• 한국진공학회:학술대회논문집
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• 한국진공학회 2016년도 제50회 동계 정기학술대회 초록집
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• pp.378.1-378.1
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• 2016

나노바이오연구분야에서 ToF-SIMS를 이용하여 lipid와 metabolite같은 저 분자의 생체물질을 측정하는데 널리 이용되어 왔다. 최근에는 고 분자량의 생체물질을 측정하기 위해서 C60, water cluster, argon cluster등의 다양한 종류의 클러스터 이온빔들이 개발되어 왔다. [1,2] 하지만 tissue샘플을 클러스터 이온빔을 이용하여 분석한 결과에서도 m/z 1500이상의 고분자를 측정한 결과는 거의 없다. 바이오샘플의 charging을 상쇄하기위해 low energy electron beam (~20 eV)을 사용하는데, low energy electron beam이 샘플에 damage를 주기 때문이다. [3] 본 연구에서는 electron fluence (electrons/cm2)가 증가함에 따라 PC(16:0/18:1(9Z)와 Ganglioside GM1의 intensity가 감소함을 알았고, low energy electron beam에 의해 생체 물질이 damage를 받을 수 있음을 확인하였다. 따라서 tissue 샘플을 SUS기판에 샘플링하고 Ar-GCIB를 이용하면 charging없이 tissue imaging을 성공적으로 수행할 수 있고, m/z 2000이상의 고 분자량의 생체물질을 측정할 수 있음을 확인하였다.

• Imaging Science in Dentistry
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• 제31권4호
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• pp.227-233
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• 2001

Purpose: The purpose of this study was to investigate the apoptosis induction in tissues constituting the craniofacial region of growing rat by irradiation. Materials and Methods: The submandibular gland, brain, articular cartilage of condylar head, and calvarium were extracted from 20-day-old rats irradiated 10 Gy. Apoptosis of each tissue was examined by DNA fragmentation and estimated quantitatively using apoptotic index on TUNEL assay. Apoptotic index of each tissue was calculated by the equation for apoptotic cells/total cells × 1,000 on the images of confocal laser scanning microscopy. Apoptotic index was analyzed statistically according to the time lapse after irradiation on the tissues. Results : In the submandibular gland, apoptotic index was significantly increased from 6 hours after irradiation showing the highest value at 12 hours and decreased to the control level at 3 days after irradiation. In the brain, apoptotic index was abruptly reached to the maximum value at 6 hours after irradiation and decreased to the control level at 4 days after irradiation. Articular cartilage and calvarium showed no or little apoptotic signals. The results obtained by the apoptotic index accorded with that of DNA fragmentation. Conclusion : Radiation was closely related with the apoptosis of submandibular gland and brain but, not related with the apoptosis of the articular cartilage of condylar head and calvarium. The changes induced by radiation of the hard tissues would not be explained by apoptosis.

• The Korean Journal of Physiology and Pharmacology
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• 제25권1호
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• pp.79-85
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• 2021

α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are differentially regulated in the nucleus accumbens (NAcc) of the brain after cocaine exposure. However, these results are supported only by biochemical and electrophysiological methods, but have not been validated with immunohistochemistry. To overcome the restriction of antigen loss on the postsynaptic target molecules that occurs during perfusion-fixation, we adopted an immersion-fixation method that enabled us to immunohistochemically quantify the expression levels of the AMPA receptor GluA1 subunit in the NAcc. Interestingly, compared to saline exposure, cocaine significantly increased the immunofluorescence intensity of GluA1 in two sub-regions, the core and the shell, of the NAcc on withdrawal day 21 following cocaine exposure, which led to locomotor sensitization. Increases in GluA1 intensity were observed in both the extra-post synaptic density (PSD) and PSD areas in the two sub-regions of the NAcc. These results clearly indicate that AMPA receptor plasticity, as exemplified by GluA1, in the NAcc can be visually detected by immunohistochemistry and confocal imaging. These results expand our understanding of the molecular changes occurring in neuronal synapses by adding a new form of analysis to conventional biochemical and electrophysiological methods.