• 대한방사성의약품학회지
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• 제1권1호
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• pp.53-61
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• 2015

Lutetium-177 ($T_{1/2}=6.71day$) is an adequate radionuclide for therapy, which has both beta emission ($E_{max}=497keV$) for therapeutic effect and gamma emission (113 and 208 keV) for imaging. $^{177}Lu$ labeled ethylenediamine-N,N,N',N'-tetrakis (methylene phosphonic acid) (EDTMP) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminomethylenephosphonate (DOTMP) have been proposed as radiopharmaceuticals for bone pain palliation. In this study, we compared radiochemistry and biodistribution of $^{177}Lu$-EDTMP and $^{177}Lu$-DOTMP. EDTMP and DOTMP were synthesized, and 1 mg of each was labeled with $^{177}Lu$ at pH 7~8 with high efficiency (>98%). For comparative biodistribution studies, $^{177}Lu$-EDTMP or $^{177}Lu$-DOTMP were injected into ICR-mice through tail vein, and then biodistribution data were obtained as percentages of injected dose per gram of tissue (% ID/g). Urine excretions of both agents in mice were checked for 7 days. Rat images were also obtained after injection of $^{177}Lu$-EDTMP or $^{177}Lu$-DOTMP. $^{177}Lu$-DOTMP (100% at 1 min) showed faster labeling than $^{177}Lu$-EDTMP (100% at 30 min). Both of them were stable at least for 21 days at room temperature. High bone uptakes were found for both $^{177}Lu$-EDTMP and $^{177}Lu$-DOTMP: 38.0 and 34.1% ID/g at 3 hr, respectively; and 33.2 and 18.8% ID/g at 7 day, respectively. Rapid excretions to urine were found for both agents ($^{177}Lu$-EDTMP: 56%, $^{177}Lu$-DOTMP: 63% at 1 day). Other organs showed very low uptakes. Rat images of both $^{177}Lu$-EDTMP and $^{177}Lu$-DOTMP showed high bone uptakes and low soft tissue uptakes. In conclusion, both $^{177}Lu$-EDTMP and $^{177}Lu$-DOTMP showed high potential as bone pain palliation agents. $^{177}Lu$-EDTMP showed higher bone uptake and slower bone clearance in mice than those of $^{177}Lu$-DOTMP.

• 대한핵의학회지
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• 제26권2호
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• pp.257-264
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• 1992

Diagnostic approaches such as angiography, ultrasound, computed tomography and nuclear magnetic resonance have limitation for contributing to the early clinical diagnosis of atherosclerosis. Recently, $^{99m}Tc-labelled$ low density lipoprotein was developed to detect early atherosclerotic lesion by external imaging with gamma camera. To determine whether $^{99m}Tc-LDL$ scintigraphy can visualize the active atherosclerotic lesion, rabbits were injected with $^{99m}Tc-LDL$, 3 months after feeding dietary fat (lanolin) and we obtained following results. 1) Labelling efficiency of $^{99m}Tc-LDL$ was $79\sim88%$. 2) Biodistribution study of normal rabbits with $^{99m}Tc-LDL$ revealed the high activities in spleen, adrenal gland, liver, kidney which are major organs of high metabolic rate of LDL. 3) Three months after feeding lanolin, serum cholesterol was markedly increased from $74{\pm}17mg/dl$ to $979{\pm}153mg/dl$ and histologic study of aorta after sacrificing the rabbit demonstrated marked atherosclerotic changes. 4) Atherosclerotic lesion of abdominal aorta which was confirmed with histologic study could be demonstrated in $^{99m}Tc-LDL$ scintigraphy after feeding lanolin for 3 months. In conclusion, the results of this preliminary investigation suggest that it may be possible to image active atheromatous lesion with $^{99m}Tc-LDL$. It is anticipated that this promising agent may allow the in vivo monitoring of preclinical atherosclerotic lesions and may be useful to evaluate the metabolic pathway of LDL in humans.

• BMB Reports
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• 제51권11호
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• pp.572-577
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• 2018

Recent studies showed that the PD-1/PD-L1 checkpoint blockade is a dramatic therapy for melanoma by enhancing antitumor immune activity. Currently, major strategies for the PD-1/PD-L1 blockade have mainly focused on the use of antibodies and compounds. Seeking an alternative approach, others employ endogenous proteins as blocking agents. The extracellular domain of PD-1 (ePD1) includes the binding site with PD-L1. Accordingly, we constructed a PD-1-based recombinantly tailored fusion protein (dFv-ePD1) that consists of bivalent variable fragments (dFv) of an MMP-2/9-targeted antibody and ePD1. The melanoma-binding intensity and antitumor activity were also investigated. We found the intense and selective binding capability of the protein dFv-ePD1 to human melanoma specimens was confirmed by a tissue microarray. In addition, dFv-ePD1 significantly suppressed the migration and invasion of mouse melanoma B16-F1 cells, and displayed cytotoxicity to cancer cells in vitro. Notably, dFv-ePD1 significantly inhibited the growth of mouse melanoma B16-F1 tumor cells in mice and in vivo fluorescence imaging showed that dFv-ePD was gradually accumulated into the B16-F1 tumor. Also the B16-F1 tumor fluorescence intensity at the tumor site was stronger than that of dFv. This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy.

• 핵의학기술
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• 제12권1호
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• pp.33-38
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• 2008

Purpose: The Gated cardiac blood pool scan is non-invasive method that a quantitative evaluation of left ventricular function. Also this scan have shown the value of radionuclide ejection fraction measurements during the course of chemotherapy as a predictor of cardiac toxicity. Therefore a reliable method of monitoring its cardiotoxic effects is necessary. the purpose of this study is to minimize the overestimate of left ventricular ejection fraction (LVEF) by modified body position to reduce the influence of scattered rays from surrounding organs of the heart in the background region of interest. Materials and Methods: Gated cardiac blood pool scan using in vivo $^{99m}Tc$-red blood cell (RBC) was carried out in 20 patients (mean $44.8{\pm}8.6$ yr) with chemotherapy for a breast carcinoma. Data acquisition requires about 600 seconds and 24 frames of one heart cycle by the multigated acquisition mode, Synchronization deteriorates toward the end of the cycle and with the distance from the trigger signal (R-wave) by ECG gating. Gated cardiac blood pool scan was studied with conventional method (supine position and the detector head in $30-45^{\circ}$ left anterior oblique position and caudal $10-20^{\circ}$ tilt) and compared with modified method (left lateral flexion position with 360 mL of drinking water). LVEF analysis was performed by using the automatically computer mode. Results: The ROI counts of modified scan method were lower than LV conventional method ($1429{\pm}251$ versus $1853{\pm}243$, <0.01). And LVEF of modified method was also decrease compared with conventional method ($58.3{\pm}5.6%$ versus $65.3{\pm}6.1%$, <0.01). Imaging analysis indicated that stomach was expanded because of water and spleen position was changed to lateral inferior compared with conventional method. Conclusion: This study shows that the modified method in MUGA reduce the influence of scattered rays from surrounding organs. Because after change the body position to left lateral flexion and drinking water, the location of spleen, left lobe of liver and stomach had changed and they could escaped from background ROI. Therefore, modified method could help to minimize the overestimate LVEF (%).

• 한국자기학회지
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• 제16권1호
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• pp.102-106
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• 2006

이 연구의 목적은 약물의 분리나 약물전달 시스템에 이용 할 수 있도록 마그네타이트 나노 입자의 표면을 개질, 즉 생체적합성, 저독성의 특성을 갖는 키토산을 이용하여 키토산이 피복된 나노 크기의 자성체 입자를 제조하는 것이다. 본 연구에서는 음향화학법을 적용한 공침 기술을 이용, 균일한 마그네타이트 나노 입자를 합성하였다. 계면활성제인 올레인산을 가하여 입자간의 응집을 막았다. 물과 계면활성제의 농도비 R=[물]/[계면활성제]를 조절하여 평균크기가 2nm에서 9nm인 마그네타이트 입자를 선택적으로 합성하였다. 이 방법을 통하여 합성된 마그네타이트 나노 인자를 염기성 수용액에 분산시켰다. 초음파를 조사하면서 키토산 용액을 서서히 가하여 마그네타이트 나노 입자의 표면을 키토산으로 피복하였다. 이때 키토산의 농도가 증가할수록 입자가 수 나노미터 크기씩 증가하는 것을 입도 분석기와 원자 현미경 관찰을 통해서 확인 할 수 있었다. 합성된 마그네타이트 분말과 키토산이 피복된 마그네타이트 나노 입자 모두 실온에서 초상자성을 보이는 것으로 나타났다.

• Journal of Ginseng Research
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• 제47권6호
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• pp.743-754
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• 2023

Background: Myocardial fibrosis post-myocardial infarction (MI) can induce maladaptive cardiac remodeling as well as heart failure. Although 20(S)-ginsenoside Rg3 (Rg3) has been applied to cardiovascular diseases, its efficacy and specific molecular mechanism in myocardial fibrosis are largely unknown. Herein, we aimed to explore whether TGFBR1 signaling was involved in Rg3's anti-fibrotic effect post-MI. Methods: Left anterior descending (LAD) coronary artery ligation-induced MI mice and TGF-β1-stimulated primary cardiac fibroblasts (CFs) were adopted. Echocardiography, hematoxlin-eosin and Masson staining, Western-blot and immunohistochemistry, CCK8 and Edu were used to study the effects of Rg3 on myocardial fibrosis and TGFBR1 signaling. The combination mechanism of Rg3 and TGFBR1 was explored by surface plasmon resonance imaging (SPRi). Moreover, myocardial Tgfbr1-deficient mice and TGFBR1 adenovirus were adopted to confirm the pharmacological mechanism of Rg3. Results: In vivo experiments, Rg3 ameliorated myocardial fibrosis and hypertrophy and enhanced cardiac function. Rg3-TGFBR1 had the 1.78×10^-7 M equilibrium dissociation constant based on SPRi analysis, and Rg3 inhibited the activation of TGFBR1/Smads signaling dose-dependently. Cardiac-specific Tgfbr1 knockdown abolished Rg3's protection against myocardial fibrosis post-MI. In addition, Rg3 downregulated the TGF-β1-mediated CFs growth together with collagen production in vitro through TGFBR1 signaling. Moreover, TGFBR1 adenovirus partially blocked the inhibitory effect of Rg3. Conclusion: Rg3 improves myocardial fibrosis and cardiac function through suppressing CFs proliferation along with collagen deposition by inactivation of TGFBR1 pathway.

• 한국콘텐츠학회논문지
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• 제10권8호
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• pp.249-256
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• 2010

사람 중간엽 줄기세포(hMSCs)를 초상자성산화철(SPIO)로 표지하여, 체외에서 세포 농도에 따른 신호의 변화를 알아보고, 흰쥐 광 혈전 뇌경색 모델에 이식하여 자기공명영상 기법 중, T2강조영상과 $T2^*$강조영상 그리고 자화강조영상의 줄기세포 검출능을 분석하고, 병리 소견과 비교하고자 하였다. 체외실험은 SPIO(Feridex I.V.$^{(R)}$)로 표지한 줄기세포 $1.56{\times}10^4$, $3.13{\times}10^4$, $6.25{\times}10^4$, $1.25{\times}10^5$, $2.5{\times}10^5$, $5{\times}10^5$ 개/$m{\ell}$, SPIO로 표지 하지 않은 $5{\times}10^5$ 개/$m{\ell}$의 세포를 Control로 준비하여 $0.5m{\ell}$튜브에 담아 T2WI, $T2^*WI$, SWI sequence로 자기공명영상을 얻었다. 체내실험은 8마리의 흰쥐를 대상으로 정수리점(bregma)에서 우측으로 2.5mm, 뒤쪽으로 2.5mm 부위에 광 혈전 뇌경색을 만들고, SPIO-hMSC $2.5{\times}10^5$ 개/$m{\ell}$, $1m{\ell}$을 꼬리 정맥에 주입하여 실험하였다. 자기공명영상은 주입 전과 주입 후 1, 3, 7 그리고, 14일째 T2WI, $T2^*$WI, SWI 영상을 얻고 정량적으로 평가하였다. 자기공명영상검사 후 흰쥐는 조직검사를 위해 희생시켰다. 체외실험 결과 CNR은 SWI, $T2^*WI$, T2WI 순으로의 높게 나왔고, 세포 농도에 따라서는 $2.5{\times}10^5$ 개/$m{\ell}$의 농도에서 가장 높게 나왔다. 체내실험에서 normal, infarction, SPIO 상호간의 CNR을 분석해본 결과 normal-infarction의 CNR은 T2WI가 가장 높게 나왔고, normal-SPIO 그리고 infarction-SPIO에서 CNR은 SWI, $T2^*WI$, T2WI순으로 나왔다. 따라서 흰쥐를 이용한 실험에서 T2WI sequence는 infarction을 잘 표현해 주고, SWI는 SPIO로 표지한 줄기세포를 normal과 infarction으로 부터 잘 구별해 주었다. 현재 임상에서 SWI는 출혈, 석회화 병변등을 쉽게 찾아내는 sequence로 사용 되고 있지만 향후에 줄기세포 치료가 인간의 질병을 치료하는 주요방안으로 자리 잡을 때에도 이식된 줄기 세포를 관찰 할 수 있는 좋은 도구가 될 것으로 기대 된다.

• 핵의학기술
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• 제14권1호
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• pp.35-39
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• 2010

감시림프절 검사에는 $^{99m}Tc$-ASC, $^{99m}Tc$-Tin colloid, $^{99m}Tc$-HSA 등이 사용되었으나 공급 제한으로 간 스캔에 사용되고 있는 $^{99m}Tc$-phytate를 대체 방사성의약품으로 사용하고 있다. 이에 저자들은 phytate의 입자 크기 분포를 알아보고 200 nm 필터 사용유무에 따른 영상을 획득 분석하여 감시림프절 검사 시 필터 사용의 적절성을 판단하고자 하였다. Photal사의 ELS-8000 장비를 이용하여 phytate kit의 입자크기 분포를 측정 하였다. 동물 실험은 생후 12~15주령, 체중 250~300 g 암컷 백서를 사용하였으며, 전신 마취 후 앙와 위로 고정시켜 영상을 획득하였다. 비교군으로 여과시키지 않은 $^{99m}Tc$-phytate를 실험군으로는 200 nm 필터를 이용하여 여과시킨 $^{99m}Tc$-phytate를 백서의 발가락 사이에 피하주사 하였다. 6마리의 백서를 3~4일 간격으로 비교군과 대조군으로 그룹을 나누어 2회씩 실시 하였으며, 주사 후 1시간 지연영상을 얻은 후 서혜부에 관심영역을 설정하였으며 비정상적인 집적이 없는 부위를 선별하여 픽셀당 카운트를 얻었다. 세포 실험은 RAW 264.7 세포를 이용하여 비교군과 실험군에 $^{99m}Tc$-phytate를 넣어주고 30분 동안 배양시켜 감마카운터를 이용하여 각각의 분 당 카운트 값을 측정하였다. 이 값들은 SPSS 12.0 프로그램을 이용하여 통계 검정하였다. Phytate를 생리식염수에 용해시킨 후 측정 결과 평균 직경은 130~650 nm가 $85{\pm}5%$ 정도였으나 200 nm 필터를 이용하여 여과시킨 후의 입자 크기는 용매 내 phytate 입자의 농도가 너무 낮아 측정할 수 없었다. 획득한 영상을 분석한 결과 비교군에서는 $60.2{\pm}4.88$ count/pixel, 실험군에서는 $58.3{\pm}5.97$ count/pixel 값을 보였다. 세포 실험에서 실험군의 카운트 값은 $17,152{\pm}1,165$ cpm이고 비교군은 $16,908{\pm}1,075$ cpm을 보였다. 동물 실험과 마찬가지로 세포 실험에서도 통계적 차이는 보이지 않았다. 이번 실험을 통하여 phytate의 사이즈가 매우 분산적이며 균일하지 못 하다는 사실을 확인하였으며, 동물 실험과 세포실험을 통한 필터 사용의 적절성을 판단한 결과 phytate를 이용한 감시림프절 검사에서 필터를 사용하는 방법은 결과에 큰 영향을 미치지 않는다는 것을 확인하였다.

• 한국방사선학회논문지
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• 제6권3호
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• pp.183-189
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• 2012

초음파 검사는 복강내 장기를 검사하는 대표적인 영상의학검사의 한 분야이며. 혈액검사는 체내 이상 징후를 임상화학적으로 검사하는 대표적인 방법이다. 지방간의 진단은 주로 복부초음파 검사와 혈액검사를 동시에 실시하여 수행하며 두 검사의 결과를 바탕으로 진단을 하게 된다. 이 경우에 실시하는 혈액검사의 기준은 TBIL, TC, AST, ALT, ALP, GGT, TG, HDL-C, GLU의 값이다. 본 연구에서는 초음파 영상에서 지방간 진단을 받은 환자의 혈액검사 정확성을 분석하여 두 종류의 검사간 정확도를 분석하고자 하였다. 2012년 1월부터 3월간 종합검진으로 복부초음파검사와 혈액검사를 동시에 받은 환자 1350명 중 초음파 검사상 지방간 판정을 받은 459명을 대상으로 초음파 검사와 혈액검사 결과가 동일한 경우는 459명 중 280명으로 약 60.8% 이며, 초음파 검사와 혈액검사의 결과가 서로 다른 경우는 179명으로 39.2%로 밝혀져 초음파 검사와 혈액검사의 진단 정확도는 60.8% 이었다. 이는 지방간의 초음파 진단시 종사자의 주관적 능력이 병변의 진단에 큰 영향을 미친 것으로 생각되어 지속적인 초음파 임상 교육이 필요할 것으로 사료된다.

• 대한방사성의약품학회지
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• 제7권2호
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• pp.119-125
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• 2021

⁸²Sr for ⁸²Rb generator was produced through the irradiation of the proton beam on the ^nat.RbCI target at the target irradiation facility installed at the end of the Rl-dedicated beamline of the 100 MeV proton linear accelerator of KOMAC (Korea Multi-purpose Accelerator Complex). The average current of the proton beam was 1.2 µA for irradiation time of 150 min. For the separation and purification of the ⁸²Sr from ^nat.RbCI irradiated, Chelex-100 resin was used. The activities of ⁸²Sr in the irradiated ^nat.RbCI target solution and after purification were 45.29 µCi and 43.4 µCi, respectively. The separation and purification yield was 95.8%. As an adsorbent to be filled in the generator for ⁸²Sr adsorption hydrous tin oxide was selected. The adsorption yield of ⁸²Sr into the generator adsorbent was > 99 %, and the total amount of ⁸²Sr adsorbed to the generator was 21.6 µCi as of the day of the ⁸²Rb elution experiment. When the elution amount was 22 mL, the maximum⁸²Rb elution yield was 93.3%, and the elution yield increased as the flow rate increased. After the eluted ⁸²Rb was filled in the correction phantom of the small PET for animals, a PET image was taken. The image scan time was set to 5 min, and the phantom PET image was successfully obtained. As results of impurity analysis on eluted ⁸²Rb using ICP-MS, ^nat.Rb stable isotopes that compete in vivo of ⁸²Rb were identified as undetected levels and were determined to be No-Carrier-Added (NCA).