Evaluation of hepatic function with 99mTc-galactosylated serum albumin scintigraphy in patients with malaria: Comparison with 99mTc-colloid scintigraphy and liver ultrasonography

Lee, Sang-Woo,Lee, Jaetae,Lee, Deog-Young,Chun, Kyung-Ah,Ahn, Byeong-Cheol,Kang, Young-Mo,Lee, Kyubo Lippincott Williams Wilkins, Inc. 2007 Nuclear medicine communications Vol.28 No.2

OBJECTIVE: Malarial parasites injected by the mosquito rapidly target hepatocytes, and hepatomegaly is commonly observed during the progress of the disease in malaria patients. To evaluate the degree of hepatic damage and functional status of hepatocytes in malaria patients, we performed liver scintigraphy using Tc-galactosylated serum albumin (GSA) prospectively and the findings were compared with those of Tc-colloid scintigraphy, ultrasonography and clinical results in the same subject. METHODS: Eight malaria patients (all male, mean age 22 years) confirmed to be infected with Plasmodium vivax underwent Tc-GSA liver scintigraphy, followed by liver ultrasonography and Tc-colloid scintigraphy using phytate within 3 days. For hepatocyte scintigraphy, anterior images of cardiac blood-pool and liver were continuously acquired for 30 min after injection of 185 MBq Tc-GSA (3 mg). In addition to visual interpretation of the images, quantitative measurement of hepatic function was performed with several functional parameters, such as hepatic uptake index (LHL15), blood clearance index (HH15) and modified receptor index (LHL/HH) calculated from the radioactivity of the liver and heart. Tc-colloid images were assessed and graded visually. Severity of hepatic dysfunction or reticuloendothelial system activation was classified as normal, mild, moderate and severe on GSA or colloid images. RESULTS: Hepatomegaly was observed in five and splenomegaly in seven of the eight patients. Serum levels of transaminase and alkaline phosphatase were mildly elevated in two. Visual assessment of GSA scintigraphy revealed normal findings in all subjects, except for mild increases in size. The mean values of LHL15, HH15 and LHL/HH were 0.928±0.014, 0.537±0.031 and 1.732±0.106, respectively. They were graded as normal in five, and near-normal to mild dysfunction in three subjects. In contrast, Tc-colloid scintigraphy revealed abnormal findings in all of the subjects, and graded as moderate in three or severe reticuloendothelial system activation in five subjects. Liver ultrasonographic findings were normal for all subjects except mild hepatomegaly. CONCLUSIONS: Malaria-induced injury of the hepatocyte is likely to be minimal whereas hepatomegaly is commonly seen during disease process. This suggests that hepatic damage in malarial infection is mainly due to involvement of the reticuloendothelial system. Tc-GSA scintigraphy can be used in differentiating hepatocellular damage from reticuloendothelial system involvement in patients with infectious disease showing hepatomegaly.

Engineering of Radioiodine-Labeled Gold Core-Shell Nanoparticles As Efficient Nuclear Medicine Imaging Agents for Trafficking of Dendritic Cells

Lee, Sang Bong,Lee, Sang-Woo,Jeong, Shin Young,Yoon, GhilSuk,Cho, Sung Jin,Kim, Sang Kyoon,Lee, In-Kyu,Ahn, Byeong-Cheol,Lee, Jaetae,Jeon, Yong Hyun American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.10

<P>The development of highly sensitive, stable, and biocompatible imaging agents allowing visualization of dendritic cell (DC) migration is one of the essential factors for effective DC-based immunotherapy. Here, we used a novel and efficient synthesis approach to develop radioiodine-124-labeled tannic acid gold core shell nanoparticles(I-124-TA-Au@AuNPs) for DC labeling and in vivo tracking of their migration using positron emission tomography (PET). I-124-TA-Au@AuNPs were produced within 40 min in high yield via straightforward tannic acid-mediated radiolabeling chemistry and incorporation of Au shell, which resulted in high radio-sensitivity and excellent chemical stability of nanoparticles in DCs and living mice. I-124-TA-Au@AuNPs demonstrated good DC labeling efficiency and did not affect cell biological functions, including proliferation and phenotype marker expression. Importantly, I-124-TA-Au@AuNPs in an extremely low amount (0.1 mg/kg) were successfully applied to track the migration of DCs to lymphoid organs (draining lymph nodes) in mice.</P>

Optimization of Dendritic Cell-Mediated Cytotoxic T-Cell Activation by Tracking of Dendritic Cell Migration Using Reporter Gene Imaging

Lee, Hongje,Lee, Ho Won,La Lee, You,Jeon, Yong Hyun,Jeong, Shin Young,Lee, Sang-Woo,Lee, Jaetae,Ahn, Byeong-Cheol Springer-Verlag 2018 Molecular imaging and biology Vol.20 No.3

Antigen-Free Radionuclide-Embedded Gold Nanoparticles for Dendritic Cell Maturation, Tracking, and Strong Antitumor Immunity

Lee, Sang Bong,Lee, Young Ju,Cho, Sung Jin,Kim, Sang Kyoon,Lee, Sang-Woo,Lee, Jaetae,Lim, Dong-Kwon,Jeon, Yong Hyun Wiley (John WileySons) 2018 Advanced Healthcare Materials Vol.7 No.9

Targeting of hepatocellular carcinoma with glypican‐3‐targeting peptide ligand

Lee, You La,Ahn, Byeong‐,Cheol,Lee, Yongjin,Lee, Sang‐,Woo,Cho, Je‐,Yoel,Lee, Jaetae John Wiley Sons, Ltd 2011 Journal of Peptide Science Vol.17 No.11

<P>Hepatocellular carcinoma is a common malignancy. The carcinoma cells express glypican‐3 (GPC‐3) on the cell membrane. GPC‐3 is also expressed in melanoma cells. Therefore, GPC‐3 might be a potential target for tumor imaging or therapy. Here, proteomic mass spectrometry was used to identify peptides that target GPC‐3‐expressing tumors. A mammalian expression vector expressing a FLAG‐GPC‐3 fusion protein was cloned for immunoprecipitation. With the use of liposomes, the vector was transfected into HepG2 (HepG2/FLAG‐GPC‐3) and HEK 293 cells, and the transfected cell lines were selected with geneticin. HepG2/FLAG‐GPC‐3 cells were used for immunoprecipitation of FLAG‐GPC‐3 fusion protein. Seven peptide candidates (L1–L7) were selected for GPC‐3‐targeting ligands by mass spectrometric analysis. The L5 peptide with 14 amino acids (Arg‐Leu‐Asn‐Val‐Gly‐Gly‐Thr‐Tyr‐Phe‐Leu‐Thr‐Thr‐Arg‐Gln) showed selective binding to the GPC‐3‐expressing tumor cells, as did a shortened L5 peptide (L5‐2) with seven amino acids (Tyr‐Phe‐Leu‐Thr‐Thr‐Arg‐Gln). These peptide ligands have potential as targeting moieties to GPC‐3‐expressing tumors for diagnostic and/or therapeutic purposes. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.</P>

Evaluation of therapeutic effects of natural killer (NK) cell‐based immunotherapy in mice using <i>in vivo</i> apoptosis bioimaging with a caspase‐3 sensor

Lee, Ho Won,Singh, Thoudam Debraj,Lee, Sang‐,Woo,Ha, Jeoung‐,Hee,Rehemtulla, Alnawaz,Ahn, Byeong‐,Cheol,Jeon, Young Hyun,Lee, Jaetae Federation of American Society for Experimental Bi 2014 The FASEB Journal Vol.28 No.7

Natural killer (NK) cell-based immunotherapy is a promising strategy for cancer treatment, and caspase-3 is an important effector molecule in NK cell-mediated apoptosis in cancers. Here, we evaluated the antitumor effects of NK cell-based immunotherapy by serial noninvasive imaging of apoptosis using a caspase-3 sensor in mice with human glioma xenografts. Human glioma cells expressing both a caspase-3 sensor as a surrogate marker for caspase-3 activation and Renilla luciferase (Rluc) as a surrogate marker for cell viability were established and referred to as D54-CR cells. Human NK92 cells were used as effector cells. Treatment with NK92 cells resulted in a time-and effector number-dependent increase in bioluminescence imaging (BLI) activity of the caspase-3 sensor in D54-CR cells in vitro. Caspase-3 activation by NK92 treatment was blocked by Z-VAD treatment in D54-CR cells. Transfusion of NK92 cells induced an increase of the BLI signal by caspase-3 activation in a dose-and time-dependent manner in D54-CR tumor-bearing mice but not in PBS-treated mice. Accordingly, sequential BLI with the Rluc reporter gene revealed marked retardation of tumor growth in the NK92-treatment group but not in the PBS-treatment group. These data suggest that noninvasive imaging of apoptosis with a caspase-3 sensor can be used as an effective tool for evaluation of therapeutic efficacy as well as for optimization of NK cell-based immunotherapy.

Radionuclide-embedded gold nanoparticles for enhanced dendritic cell-based cancer immunotherapy, sensitive and quantitative tracking of dendritic cells with PET and Cerenkov luminescence

Lee, Sang Bong,Ahn, Su Bi,Lee, Sang-Woo,Jeong, Shin Young,Ghilsuk, Yoon,Ahn, Byeong-Cheol,Kim, Eun-Mi,Jeong, Hwan-Jeong,Lee, Jaetae,Lim, Dong-Kwon,Jeon, Yong Hyun Nature Publishing Group 2016 NPG Asia Materials Vol.8 No.-

<P>Radionuclide-embedded gold nanoparticles (RIe-AuNPs) were developed as a highly sensitive and stable nuclear and optical imaging agent for efficient dendritic cell (DC)-based immunotherapy and sensitive tracking of DC-migration to lymph nodes. The RIe-AuNPs were synthesized via simple and straightforward DNA-based radiolabeling chemistry and additional Au shell formation strategies, leading to high radiosensitivity and excellent in vivo stability. The RIe-AuNPs exert no adverse effects on the biological functions of DCs, and labeled DCs show strong antitumor immunity for lung cancer. Furthermore, the high radiosensitivity of the RIe-AuNPs allows for sensitive and long-term monitoring of DC migration to draining lymph nodes. The developed Cerenkov radiation-based optical imaging approach provides quantitative and sensitive results comparable with that of positron emission tomography imaging. These results highlight the strong potential of the RIe-AuNPs as a highly sensitive and stable nuclear and optical imaging platform for future bioimaging application such as cell tracking and tumor imaging.</P>

<i>In vivo</i> detection of sentinel lymph nodes with PEGylated crushed gold shell @ radioactive core nanoballs

Lee, Sang Bong,Li, Yinghua,Lee, In-Kyu,Cho, Sung Jin,Kim, Sang Kyoon,Lee, Sang-Woo,Lee, Jaetae,Jeon, Yong Hyun THE KOREAN SOCIETY OF INDUSTRIAL AND ENGINEERING 2019 JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY -S Vol.70 No.-

<P><B>Abstract</B></P> <P>Positron-emitting radioactive isotope-labeled gold nanomaterials are suitable imaging agents in biomedical imaging owing to their high sensitivity, straightforward clinical translation, adequate information regarding clinical safety, and their application in another new imaging modality, Cerenkov luminescent imaging. This study aimed to investigate the potential application of PEGylated crushed gold shell @ radioiodine-labeled core nanoparticles (PEG-<SUP>124</SUP>I-Au@AuCBs) in detecting sentinel lymph nodes (SLNs) in mice <I>in vivo</I>, using the dual imaging modality of positron emission tomography and Cerenkov luminescence imaging (PET/CLI). PEG-<SUP>124</SUP>I-Au@AuCBs were non-toxic and did not affect cellular function in normal and immune cells. <I>In vivo</I> PET imaging revealed the selective accumulation of PEG-<SUP>124</SUP>I-Au@AuCBs in SLNs proximal to the site of injection 1h after injection and radioactivity was detected from the SLN until 24h. Consistently, the SLNs were also visualized using <I>in vivo</I> CLI at 24h, consistent with the findings of <I>ex vivo</I> bio-distribution and histological analyses. Therefore, PEG-<SUP>124</SUP>I-Au@AuCBs are suitable multimodal contrast agents for <I>in vivo</I> SLN mapping in pre- or intraoperative guidance.</P> <P><B>Graphical abstract</B></P> <P>The PEGylated crushed gold shell @ radioiodine labeled core nanoparticles(PEG-<SUP>124</SUP>I-Au@AuCBs) as a highly sensitive and stable radioactive lymphatic tracer is introduced for non-invasive mapping of sentinel lymph nodes, using the dual imaging modality of positron emission tomography-Cerenkov luminescence imaging (PET/CLI).</P> <P>[DISPLAY OMISSION]</P>

F-18 Fluorodeoxyglucose PET/CT and Post Hoc PET/MRI in a Case of Primary Meningeal Melanomatosis

Lee, Hong Je,Ahn, Byeong-Cheol,Hwang, Seong Wook,Cho, Suk Kyong,Kim, Hae Won,Lee, Sang-Woo,Hwang, Jeong-Hyun,Lee, Jaetae The Korean Society of Radiology 2013 KOREAN JOURNAL OF RADIOLOGY Vol.14 No.2

<P>Primary meningeal melanomatosis is a rare, aggressive variant of primary malignant melanoma of the central nervous system, which arises from melanocytes within the leptomeninges and carries a poor prognosis. We report a case of primary meningeal melanomatosis in a 17-year-old man, which was diagnosed with <SUP>18</SUP>F-fluorodeoxyglucose (F-18 FDG) PET/CT, and post hoc F-18 FDG PET/MRI fusion images. Whole-body F-18 FDG PET/CT was helpful in ruling out the extracranial origin of melanoma lesions, and in assessing the therapeutic response. Post hoc PET/MRI fusion images facilitated the correlation between PET and MRI images and demonstrated the hypermetabolic lesions more accurately than the unenhanced PET/CT images. Whole body F-18 FDG PET/CT and post hoc PET/MRI images might help clinicians determine the best therapeutic strategy for patients with primary meningeal melanomatosis.</P>

분화 갑상선암 환자의 수술후 잔여갑상선조직 및 전이병소의 진단 : Tc-99m Pertechnetate 스캔과 고용량 옥소 치료 후 I-131 스캔의 비교 Comparison between Tc-99m Pertechnetate Scan and High Dose I-131 Therapy Scan

이주령,안병철,정신영,이재태,이규보 대한핵의학회 2003 핵의학 분자영상 Vol.37 No.2

목적 : 갑상선 절제술을 받은 분화 갑상선암 환자의 경우 잔여 갑상선 조직이나 전이 병소를 찾기 위해서는 진단적 I-131 스캔이 주로 사용되고 있으나, I-131 스캔은 갑상선 호르몬 중지가 필요하고, 방사성 옥소 투여후 2~3일에 영상을 얻어야 하며, 기절 현상이 발생할 수 있다는 점 등의 단점이 있다. 이에 비하여 Tc-99m 스캔은 검사가 용이하고 영상의 질이 좋아 진단적 I-131 스캔을 대체할 수 있을 지에 대한 논란이 있다. 이에 저자들은 고용량 방사성옥소 치료 후 시행한 I-131 스캔을 기준으로 하여 치료전 시행한 Tc-99m 스캔의 진단성능을 알아보고자 하였다. 대상 및 방법 : 갑상선 절제술을 받은 분화 갑상선암 환자 135명을 대상 (여: 114, 연령: 45±15.3세)으로 하였고, 방사성옥소 치료 병력이 있는 환자는 23명 (1회 16명, 2회 4명, 3회 3명)이었다. 갑상선 호르몬 복용을 4주간 중단한 후 370 MBq의 Tc-99m pertechnetate를 정맥주사 한 20분 후에 전경부의 평면 및 바늘구멍 Tc-99m 스캔 영상을 얻었고, 3.7~7.4 GBq의 I-131 옥소를 경구 복용한 3일 후 전경부 평면 및 바늘구멍 I-131 스캔 영상을 얻었다. Tc-99m 스캔과 I-131 스캔은 최대 7일 간격이내에 시행되었다. 영상의 판독은 두명의 핵의학 전문의가 함께 합의에 의하여 시간적으로 섭취여부 및 섭취부위의 개수를 구하였다. 결과 : 대상 환자 모두는 혈청 TSH는 30㎖U/L 이상으로, 갑상선 기능저하증 상태에 있었다. 전체 환자 135명 가운데 65명 (48.1%)에서 Tc-99m 스캔과 I-131 스캔이 불일치 소견을 보였다. 두 스캔사이에 불일치를 보인 환자 가운데 23명 (35.4%)은 Tc-99m 스캔에서는 전경부 방사능 섭취부위가 발견되지 않았으나 I-131 스캔에서 옥소 섭취부위가 발견된 경우이며, 42명 (64.6%)은 Tc-99m 스캔보다 I-131 스캔에서 전경부옥소 섭취부위가 더 많이 발견되었다. 방사성 옥소치료병력이 없는 환자 112명 가운데 51명 (45.5%)은 Tc-99m 스캔과 I-131 스캔이 불일치 소견을 보였다. 이들 가운데 Tc-99m 스캔에서 전경부 방사능 섭취부위가 발견되지 않았던 11명 가운데 9명 (81.8%)은 I-131 스캔에서 옥소 섭취부위가 발견되었다. 수술후 방사성옥소 치료를 받은 병력이 있는 전체 23명은 Tc-99m 스캔상 전경부 섭취부위가 발견되지 않았으나, 이들 중 14명 (60.9%)은 I-131 스캔에서 전경부의 옥소 섭취부위가 나타났었다. 결론 : 이상의 결과로 보아 분화 갑상선암 환자의 수술후 잔여 갑상선조직이나 전이병소를 평가시 Tc-99m 스캔은 고용량의 방사성 옥소 치료후 얻은 I-131 스캔을 기준으로 볼때 진단적 예민도가 낮았으며, 특히, 방사성 옥소 치료병력을 가진 환자의 경우, 진단적 유용성이 없는 것으로 생각된다. Purpose : To evaluate diagnostic sensitivity of nuclear imaging in the detection of residual thyroid tissue and metastatic lesion, we have compared neck scintigrams with Tc-99m pertechnetate (Tc-99m scan) and high dose I-131 iodide (I-131 scan) in patients with differentiated thyroid cancer. Subjects and Methods : One hundred thirty-five thyroidectomized patients for differentiated thyroid cancer were enrolled in this study. Twenty-three had a previous history of radioiodine Therapy. Planar and pin-hole images of anterior neck with Tc-99m were acquired at 20 minutes after injection, followed by I-131 scan three days after high-dose radioiodine therapy within 7 days interval. Patients were asked to discontinue thyroid hormone replacement more than 4 weeks. Results : All subjects were in hypothyroid state. Seventy out of 135 patients (51.9%) showed concordant findings between Tc-99m and I-131 scans. I-131 scan showed higher number of uptake foci in all of 65 patients showing discordant finding. Tc-99m scan showed no thyroid bed uptake in 34 patients, whereas 23 of them (67.6%) showed bed uptake in I-131 scan. Tc-99m scan did not show any uptake in thyroid bed in 11 or 112 patients without previous history of radioiodine therapy, but 9 of them showed bed uptake in I-131 scan. Tc-99m scan showed no bed uptake in all of the 23 patients with previous history of radioiodine therapy, in contrast 14 of them (60.9%) showed bed uptake in I-131 scan. Conclusion : These results suggest that Tc-99m scan has poor detectability for residual thyroid tissue or metastatic lesion in thyroidectomized differentiated thyroid cancer patients, compared to high dose I-131 therapy scan. Tc-99m scan could not detect any remnant tissue or metastatic lesion in patients with previous history of radioiodine treatment, especially.