Molecular imaging application of iron oxide nanoradiomaterial

유란지,박지용,최태현,김진실,이윤상 대한방사성의약품학회 2021 Journal of radiopharmaceuticals and molecular prob Vol.7 No.2

Various iron oxide nanoparticle-based radiomaterials(IO-NRM) can be used for multimodal imaging of magnetic resonance imaging and molecular imaging, can be easily sized, can be easily functionalized, and have biocompatibility, making them a very good platform for molecular imaging. Based on the previously revealed molecular imaging technology of iron oxide nanoparticles, this paper introduces the in vivo distribution and use in various diseases through iron oxide nanoparticles-based radiolabeled compounds for diagnosis and treatment of iron oxide nanoparticles-based molecular imaging platforms. We would like to look forward to its potential as a radiopharmaceutical.

Molecular imaging of polarized macrophages in tumors

유란지,이윤상 대한방사성의약품학회 2021 Journal of radiopharmaceuticals and molecular prob Vol.7 No.1

Diversity and flexibility are two typical hallmarks of macrophages. Two types of macrophages, M1(classically activated macrophages) and M2(alternatively activated macrophages) exist at both ends of the commonly known macrophage polarization. M1 macrophages have inflammatory properties and are primarily responsible for defending against invading bacteria in our body. On the other hand, M2 macrophages are involved in antiinflammatory responses and tissue remodeling. Polarized migration of macrophages is of increasing interest in regulating the initiation, generation, and resting phases of inflammatory diseases. In this review, it intend to discuss the properties and functions of tumor-associated macrophages based on polarized macrophages that affect inflammatory diseases. In addition, the purpose of this study is to investigate a molecular imaging approach that targets macrophages that affect tumor growth by controlling the polarization of macrophages that affect tumor diagnosis and treatment.

Intratumoral distribution of 64Cu-ATSM and 18F-FDG in VX2 tumor xenografted rabbit

유란지,이지웅,이교철,안광일,오인옥,정위섭,박지애,김경민,최양규,강주현,임상무,이용진 대한방사성의약품학회 2015 Journal of radiopharmaceuticals and molecular prob Vol.1 No.2

64Cu-labeled diacetyl-bis(N4-methylthiosemicarbazone) is a promising agent for internal radiation therapy and imaging of hypoxic tissues. In the study, we confirmed hypoxia regions in VX2 tumor implanted rabbits with injection 64Cu-ATSM and 18F-FDG using positron emission tomography (PET)/computed tomography (CT). PET images with 18F-FDG and 64Cu-ATSM were obtained for 40 min by dynamic scan and additional delayed PET images of 64Cu-ATSM the acquired up to 48 hours. Correlation between intratumoral O2 level and 64Cu-ATSM PET image was analyzed. 64Cu-ATSM and 18F-FDG were intravenously co-injected and the tumor was dissected and cut into slices for a dual-tracer autoradiographic analysis. In the PET imaging, 64Cu-ATSM in VX2 tumors displayed a specific uptake in hypoxic region for 48 h. The uptake pattern of 64Cu-ATSM in VX2 tumor at 24 and 48 h did not match to the 18F-FDG. Through ROI analysis, in the early phase (dynamic scan), 18F-FDG has positive correlation with 64Cu-ATSM but late phase (24 and 48 h) of the 64Cu-ATSM showed negative correlation with 18F-FDG. High uptake of 64Cu-ATSM in hypoxic region was responded with significant decrease of oxygen pressure, which confirmed by 64Cu-ATSM PET imaging and autoradiographic analysis. In conclusion, 64Cu-ATSM can utilize for specific targeting of hypoxic region in tumor, and discrimination between necrotic- and viable hypoxic tissue. J Radiopharm Mol Probes 1(2):123-129, 2015

KSNM60: The History of Radiopharmaceutical Sciences in Korea

유란지,이윤상,Lee Kyo Chul,김동욱,김동연,최연성,정재민 대한핵의학회 2022 핵의학 분자영상 Vol.56 No.3

A number of researchers in Korea have tried to set-up the production of radionuclides and develop new radiopharmaceuticals for several decades. Thanks to their 60-year endeavor to advance the field of radiopharmaceutical sciences, now we have a lot of research units and facilities in Korea. Still, there are huge number of issues to be solved in radiopharmaceutical sciences; however, our efforts will be continued to develop new radiopharmaceuticals and to apply the new radiopharmaceuticals into nuclear medicine field.

Evaluation of 64Cu-labeled PET Tracers for Imaging Acute Inflammation and Endogenous Hydrogen Sulfide

서혜연,유란지,정재민,이윤상 대한방사성의약품학회 2024 Journal of radiopharmaceuticals and molecular prob Vol.9 No.2

Hydrogen sulfide (H2S), recognized as the third gasotransmitter with specific implications for inflammation and hypoxia, exhibits affinity for 64Cu immobilization. This study explores the viability of 64Cu-labeled PET tracers in detecting endogenous H2S. In vitro reactivity experiments involved evaluating the interaction between various concentrations of NaHS and 64Cu-labeled chelators at 37℃ in a shaking incubator. In vivo molecular PET imaging studies were conducted using two distinct mouse models. An acute inflammation model, induced with carrageenan, involved administering 2.22 MBq/100 μL of [64Cu]Cu-ATSM or [64Cu]Cu-Cyclen intravenously 4 hours post-inflammation induction, with subsequent PET imaging in static 5 min mode. For the NaHS implantation model, NaHS dissolved in Matrigel was subcutaneously injected into the right dorsal region of BALB/c mice, followed by intravenous injection of radiotracers (2.22 MBq/100 μL) 1 hour later, and subsequent PET imaging. The optimized labeling condition involved dissolving 10 μg of chelators in ammonium acetate buffer and reacting at 60℃ for 20 minutes. Both [64Cu]Cu-Cyclen and [64Cu]Cu-ATSM reacted with various concentrations of NaHS to form insoluble 64CuS. High uptake of [64Cu]Cu-ATSM and [64Cu]Cu-Cyclen in acute inflammatory lesions in the mouse right footpad and the NaHS implantation model suggests their potential as imaging agents for inflammation and H2S in vivo. In conclusion, optimized [64Cu]Cu-ATSM and [64Cu]Cu-Cyclen labeling conditions for endogenous H2S imaging were established, confirming insoluble 64CuS both in vitro and in vivo. [ 64Cu]Cu-ATSM and [64Cu]Cu-Cyclen hold promise as diagnostic agents targeting endogenous H2S in various diseases associated with inflammation and hypoxia.

Korean Red Ginseng Extract Alleviates Atherosclerotic Lesions in Apolipoprotein E Knockout Mice

정의숙,서진희,유란지,이용진,강주현,나승열,최양규 한국식품과학회 2014 Food Science and Biotechnology Vol.23 No.4

This study was to evaluate the anti-atheroscleroticeffect of Korean red ginseng (KRG) in apolipoprotein Eknockout (ApoE KO) mice. Female ApoE KO mice weredivided into 2 groups and were treated via intragastricinoculation for 21 weeks. The body weight increasedgradually in both the KRG extract inoculation group andthe control group inoculated with saline. Plaque lesionareas in the aortic sinus were reduced largely in the KRGinoculation group than in the control group. Triglycerideand inflammatory cytokines such as monocyte chemoattractantprotein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) were significantly reduced in the KRG inoculationgroup. Additionally, the KRG inoculation group showedsignificantly lower cardiovascular inflammation by 18Ffluoro-2-deoxy-D-glucose positron emission tomography/computed tomography compared to that in the controlgroup. Taken together, KRG alleviates atherosclerotic lesionsthrough MCP-1 and TNF-α suppression. These resultssuggest that KRG could be a valuable therapeutic strategyfor the treatment of atherosclerosis.

Development of High Intensity Focused Ultrasound (HIFU) Mediated AuNP-liposomal Nanomedicine and Evaluation with PET Imaging

김지윤,신운철,박지용,유란지,Soeku Bae,Tae Hyeon Choi,Kyuwan Kim,Young Chan Ann,Jin Sil Kim,Yu Jin Shin,이호규,이용진,이교철,김성욱,이윤상 대한방사성의약품학회 2023 Journal of radiopharmaceuticals and molecular prob Vol.9 No.1

Liposomes as drug delivery system have proved useful carrier for various disease, including cancer. In addition, perfluorocarbon cored microbubbles are utilized in conjunction with high-intensity focused-ultrasound (HIFU) to enable simultaneous diagnosis and treatment. However, microbubbles generally exhibit lower drug loading efficiency, so the need for the development of a novel liposome-based drug delivery material that can efficiently load and deliver drugs to targeted areas via HIFU. This study aims to develop a liposome-based drug delivery material by introducing a substance that can burst liposomes using ultrasound energy and confirm the ability to target tumors using PET imaging. Liposomes (Lipo-DOX, Lipo-DOX-Au, Lipo-DOX-Au-RGD) were synthesized with gold nanoparticles using an avidin-biotin bond, and doxorubicin was mounted inside by pH gradient method. The size distribution was measured by DLS, and encapsulation efficiency of doxorubicin was analyzed by UV-vis spectrometer. The target specificity and cytotoxicity of liposomes were assessed in vitro by glioblastoma U87mg cells to HIFU treatment and analyzed using CCK-8 assay, and fluorescence microscopy at 6-hour intervals for up to 24 hours. For the in vivo study, U87mg model mouse were injected intravenously with 1.48 MBq of 64Cu-labeled Lipo-DOX-Au and Lipo-DOX-Au-RGD, and PET images were taken at 0, 2, 4, 8, and 24 hours. As a result, the size of liposomes was 108.3 ± 5.0 nm at Lipo-DOX-Au and 94.1 ± 12.2 nm at Lipo-DOX-Au-RGD, and it was observed that doxorubicin was mounted inside the liposome up to 52%. After 6 hours of HIFU treatment, the viability of U87mg cells treated with Lipo-DOX-Au decreased by around 20% compared to Lipo-DOX, and Lipo-DOX-Au-RGD had a higher uptake rate than Lipo-DOX. In vivo study using PET images, it was confirmed that 64Cu-Lipo-DOX-Au-RGD was taken up into the tumor immediately after injection and maintained for up to 4 hours. In this study, drugs released from liposomes-gold nanoparticles via ultrasound and RGD targeting were confirmed by non-invasive imaging. In cell-level experiments, HIFU treatment of gold nanoparticle-coupled liposomes significantly decreased tumor survival, while RGD-liposomes exhibited high tumor targeting and rapid release in vivo imaging. It is expected that the combination of these models with ultrasound is served as an effective drug delivery material with therapeutic outcomes.

[18F]FET PET is a useful tool for treatment evaluation and prognosis prediction of anti-angiogenic drug in an orthotopic glioblastoma mouse model

김옥선,박장우,이은상,유란지,김원일,이교철,심재훈,정혜경 한국실험동물학회 2018 Laboratory Animal Research Vol.34 No.4

O-2-18F-fluoroethyl-l-tyrosine ([18F]FET) has been widely used for glioblastomas (GBM) in clinical practice, although evaluation of its applicability in non-clinical research is still lacking. The objective of this study was to examine the value of [18F]FET for treatment evaluation and prognosis prediction of anti-angiogenic drug in an orthotopic mouse model of GBM. Human U87MG cells were implanted into nude mice and then bevacizumab, a representative anti-angiogenic drug, was administered. We monitored the effect of anti-angiogenic agents using multiple imaging modalities, including bioluminescence imaging (BLI), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT). Among these imaging methods analyzed, only [18F]FET uptake showed a statistically significant decrease in the treatment group compared to the control group (P=0.02 and P=0.03 at 5 and 20 mg/kg, respectively). This indicates that [18F]FET PET is a sensitive method to monitor the response of GBM bearing mice to anti-angiogenic drug. Moreover, [18F]FET uptake was confirmed to be a significant parameter for predicting the prognosis of anti-angiogenic drug (P=0.041 and P=0.007, on Days 7 and 12, respectively, on Pearson’s correlation; P=0.048 and P=0.030, on Days 7 and 12, respectively, on Cox regression analysis). However, results of BLI or MRI were not significantly associated with survival time. In conclusion, this study suggests that [18F]FET PET imaging is a pertinent imaging modality for sensitive monitoring and accurate prediction of treatment response to anti-angiogenic agents in an orthotopic model of GBM.

소동물 폐종양의 정량적 개선을 위한 내부 움직임 평가

유정우,우상근,이용진,김경민,김진수,이교철,박상준,유란지,강주현,지영훈,정용현,김병일,임상무,Yu, Jung-Woo,Woo, Sang-Keun,Lee, Yong-Jin,Kim, Kyeong-Min,Kim, Jin-Su,Lee, Kyo-Chul,Park, Sang-Jun,Yu, Ran-Ji,Kang, Joo-Hyun,Ji, Young-Hoon,Chung, Y 한국의학물리학회 2011 의학물리 Vol.22 No.3

이 연구에서는 폐종양의 정량적 개선을 위하여 분자체를 이용하여 내부 움직임을 측정하고 평가된 데이터를 기반으로 소동물 PET 영상내의 폐종양을 국소화하고자 하였다. 소동물 폐 영역의 내부 움직임은 방사성물질을 흡착한 분자체를 이용하여 소동물 폐 영역에 부착함으로써 구현하였다. 폐 영역의 내부 움직임 표적으로 사용된 분자체는 약 37 kBq의 Cu-64를 흡착시켜 폐종양을 모사하였다. 소동물 PET 영상은 Siemens Inveon 스캐너를 이용하여 획득하였으며 외부 움직임 데이터는 트리거 생성 장치인 BioVet을 이용하였다. SD-Rat PET 영상은 $^{18}F$-FDG 37 MBq/0.2 mL을 미정맥으로 주사하고 60분 후 20분간 데이터를 획득하였다. 리스트모드 데이터의 각 선응답은 외부 트리거 장치에 의해 획득된 트리거신호를 이용하여 2 bin에서 16 bin으로 사이노그램을 획득하였다. 획득된 사이노그램 데이터는 OSEM 2D 알고리즘을 이용하여 4회의 반복으로 재구성하였다. 종양의 정량적 분석을 위한 PET 영상은 종양을 묘사한 분자체 영역에 관심영역을 설정하고 계수와 SNR 그리고 FWHM을 이용하여 평가하였다. 움직임 표적으로 사용된 분자체의 크기는 $1.59{\times}2.50mm$이었으며, 기준 영상으로 획득한 체외 분자체 수직 및 수평 FWHM은 $2.91{\times}1.43mm$이었다. 정적영상과 4 bin 그리고 8 bin 영상에서의 수직 FWHM은 각각 3.90 mm, 3.74 mm, 3.16 mm이었으며 수평 FWHM은 각각 2.21 mm, 2.06 mm, 1.60 mm이었다. 정적영상, 4 bin, 8 bin, 12 bin 그리고 16 bin의 계수 값은 각각 4.10, 4.83, 5.59, 5.38, 5.31이었다. 정적영상, 4 bin, 8 bin, 12 bin 그리고 16 bin의 SNR은 4.18, 4.05, 4.22, 3.89, 3.58이었다. FWHM은 게이트 수의 증가에 따라 계속 향상됨을 확인하였다. 그러나 계수 값과 SNR은 게이트 수의 증가에 따라 계속 향상되지 않고 특정 bin 수에서 가장 높은 값을 보여 소동물 폐 영역에서의 종양 영상화시 SNR의 손실을 최소화하면서 향상된 계수 값을 얻을 수 있는 게이트 수를 획득하였다. 내부 움직임 측정은 최적화된 종양 국소화 영상을 획득할 수 있으며 외부 움직임 모니터링 시스템을 사용하지 않고 장기별 움직임 예측 모델링을 위한 유용한 방법이 될 것으로 기대된다. The purpose of this study was to estimate internal motion using molecular sieve for quantitative improvement of lung tumor and to localize lung tumor in the small animal PET image by evaluated data. Internal motion has been demonstrated in small animal lung region by molecular sieve contained radioactive substance. Molecular sieve for internal lung motion target was contained approximately 37 kBq Cu-64. The small animal PET images were obtained from Siemens Inveon scanner using external trigger system (BioVet). SD-Rat PET images were obtained at 60 min post injection of FDG 37 MBq/0.2 mL via tail vein for 20 min. Each line of response in the list-mode data was converted to sinogram gated frames (2~16 bin) by trigger signal obtained from BioVet. The sinogram data was reconstructed using OSEM 2D with 4 iterations. PET images were evaluated with count, SNR, FWHM from ROI drawn in the target region for quantitative tumor analysis. The size of molecular sieve motion target was $1.59{\times}2.50mm$. The reference motion target FWHM of vertical and horizontal was 2.91 mm and 1.43 mm, respectively. The vertical FWHM of static, 4 bin and 8 bin was 3.90 mm, 3.74 mm, and 3.16 mm, respectively. The horizontal FWHM of static, 4 bin and 8 bin was 2.21 mm, 2.06 mm, and 1.60 mm, respectively. Count of static, 4 bin, 8 bin, 12 bin and 16 bin was 4.10, 4.83, 5.59, 5.38, and 5.31, respectively. The SNR of static, 4 bin, 8 bin, 12 bin and 16 bin was 4.18, 4.05, 4.22, 3.89, and 3.58, respectively. The FWHM were improved in accordance with gate number increase. The count and SNR were not proportionately improve with gate number, but shown the highest value in specific bin number. We measured the optimal gate number what minimize the SNR loss and gain improved count when imaging lung tumor in small animal. The internal motion estimation provide localized tumor image and will be a useful method for organ motion prediction modeling without external motion monitoring system.

Establishment of a mouse model of 70% lethal dose by total-body irradiation

류승현,박종형,정의숙,최수영,함승훈,박진일,전희연,김준영,유란지,이용진,우상근,최양규 한국실험동물학회 2016 Laboratory Animal Research Vol.32 No.2

Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-weekold and 8-week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model.