• Title/Summary/Keyword: Lu-177

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Dosimetric Analysis of a Phase I Study of PSMA-Targeting Radiopharmaceutical Therapy With [177Lu]Ludotadipep in Patients With Metastatic Castration-Resistant Prostate Cancer

  • Seunggyun Ha;Joo Hyun O;Chansoo Park;Sun Ha Boo;Ie Ryung Yoo;Hyong Woo Moon;Dae Yoon Chi;Ji Youl Lee
    • Korean Journal of Radiology
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    • v.25 no.2
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    • pp.179-188
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    • 2024
  • Objective: 177Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [177Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [177Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [177Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organand tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. Results: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. Conclusion: [177Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

Thermal-hydraulic safety analysis of radioisotope production in HANARO using MCNP6 and COMSOL multiphysics: A feasibility study

  • Taeyun Kim;Bo-Young Han;Seongwoo Yang;Jaegi Lee ;Gwang-Min Sun;Byung-Gun Park;Sung-Joon Ye
    • Nuclear Engineering and Technology
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    • v.55 no.11
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    • pp.3996-4001
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    • 2023
  • The High-flux Advanced Neutron Application Reactor (HANARO) produces radioisotopes (RIs) (131I, 192Ir, etc.) through neutron irradiation on various RI production targets. Among them, 177Lu and 166Ho are particularly promising owing to their theranostic characteristics that facilitate simultaneous diagnosis and treatment. Prior to neutron irradiation, evaluating the nuclear heating of the RI production target is essential for ensuring the thermal-hydraulic safety of HANARO. In this study, the feasibility of producing 177Lu and 166Ho using irradiation holes of HANARO was investigated in terms of thermal-hydraulic safety. The nuclear heating rates of the RI production target by prompt and delayed radiation were calculated using MCNP6. The calculated nuclear heating rates were used as an input parameter in COMSOL Multiphysics to obtain the temperature distribution in an irradiation hole. The degree of temperature increase of the 177Lu and 166Ho production targets satisfied the safety criteria of HANARO. The nuclear heating rates and temperature distribution obtained through the in silico study are expected to provide valuable insight into the production of 177Lu and 166Ho using HANARO.

Verification of the Cancer Therapeutic Efficacy of Lutetium-177 Using Gene Expression (유전자 발현을 활용한 루테튬 (177Lu)의 암 치료 효능 검증)

  • Da-Mi Kim;So-Young Lee;Jae-Cheong Lim;KangHyuk Choi
    • Journal of Radiation Industry
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    • v.17 no.4
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    • pp.417-425
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    • 2023
  • Lutetium(177Lu), with its theranostic properties, is one of the most widely used radioisotopes and has a large share of the radiopharmaceutical market due to its many applications and targeted therapeutic research using lutetium-based radiopharmaceuticals. However, lutetium-based radiopharmaceuticals currently approved by the US Food and Drug Administration (FDA) are limited to the indications of gastrointestinal cancer, pancreatic neuroendocrine cancer and metastatic castration-resistant prostate cancer. To overcome these limitations, we aimed to demonstrate the feasibility of expanding the use of lutetium-based radiopharmaceuticals by verifying the availability and therapeutic efficacy of lutetium produced in a research reactor(HANARO). In this study, we confirmed the therapeutic efficacy of lutetium by using cancer cells from different types of cancer. In addition, we selected cancer biomarkers based on characteristics common to various cancer cells and compared and evaluated the therapeutic efficacy of lutetium by regulating the expression of target genes. The results showed that modulation of cancer biomarker gene expression resulted in higher therapeutic efficacy compared to lutetium alone. In conclusion, this study verified the potential use and therapeutic efficacy of lutetium based on the production of a research reactor (HANARO), providing fundamental evidence for the development of lutetium-based radiopharmaceuticals and the expansion of their indications.

A study on Broad Quantification Calibration to various isotopes for Quantitative Analysis and its SUVs assessment in SPECT/CT (SPECT/CT 장비에서 정량분석을 위한 핵종 별 Broad Quantification Calibration 시행 및 SUV 평가를 위한 팬텀 실험에 관한 연구)

  • Hyun Soo, Ko;Jae Min, Choi;Soon Ki, Park
    • The Korean Journal of Nuclear Medicine Technology
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    • v.26 no.2
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    • pp.20-31
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    • 2022
  • Purpose Broad Quantification Calibration(B.Q.C) is the procedure for Quantitative Analysis to measure Standard Uptake Value(SUV) in SPECT/CT scanner. B.Q.C was performed with Tc-99m, I-123, I-131, Lu-177 respectively and then we acquired the phantom images whether the SUVs were measured accurately. Because there is no standard for SUV test in SPECT, we used ACR Esser PET phantom alternatively. The purpose of this study was to lay the groundwork for Quantitative Analysis with various isotopes in SPECT/CT scanner. Materials and Methods Siemens SPECT/CT Symbia Intevo 16 and Intevo Bold were used for this study. The procedure of B.Q.C has two steps; first is point source Sensitivity Cal. and second is Volume Sensitivity Cal. to calculate Volume Sensitivity Factor(VSF) using cylinder phantom. To verify SUV, we acquired the images with ACR Esser PET phantom and then we measured SUVmean on background and SUVmax on hot vials(25, 16, 12, 8 mm). SPSS was used to analyze the difference in the SUV between Intevo 16 and Intevo Bold by Mann-Whitney test. Results The results of Sensitivity(CPS/MBq) and VSF were in Detector 1, 2 of four isotopes (Intevo 16 D1 sensitivity/D2 sensitivity/VSF and Intevo Bold) 87.7/88.6/1.08, 91.9/91.2/1.07 on Tc-99m, 79.9/81.9/0.98, 89.4/89.4/0.98 on I-123, 124.8/128.9/0.69, 130.9, 126.8/0.71, on I-131, 8.7/8.9/1.02, 9.1/8.9/1.00 on Lu-177 respectively. The results of SUV test with ACR Esser PET phantom were (Intevo 16 BKG SUVmean/25mm SUVmax/16mm/12mm/8mm and Intevo Bold) 1.03/2.95/2.41/1.96/1.84, 1.03/2.91/2.38/1.87/1.82 on Tc-99m, 0.97/2.91/2.33/1.68/1.45, 1.00/2.80/2.23/1.57/1.32 on I-123, 0.96/1.61/1.13/1.02/0.69, 0.94/1.54/1.08/0.98/ 0.66 on I-131, 1.00/6.34/4.67/2.96/2.28, 1.01/6.21/4.49/2.86/2.21 on Lu-177. And there was no statistically significant difference of SUV between Intevo 16 and Intevo Bold(p>0.05). Conclusion Only Qualitative Analysis was possible with gamma camera in the past. On the other hand, it's possible to acquire not only anatomic localization, 3D tomography but also Quantitative Analysis with SUV measurements in SPECT/CT scanner. We could lay the groundwork for Quantitative Analysis with various isotopes; Tc-99m, I-123, I-131, Lu-177 by carrying out B.Q.C and could verify the SUV measurement with ACR phantom. It needs periodic calibration to maintain for precision of Quantitative evaluation. As a result, we can provide Quantitative Analysis on follow up scan with the SPECT/CT exams and evaluate the therapeutic response in theranosis.

Review of Radionuclide Treatment for Neuroendocrine Tumors (신경내분비종양의 방사성핵종 치료)

  • Jeong, Hwan-Jeong
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.2
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    • pp.90-95
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    • 2006
  • Neuroendocrine tumors (NETs) consist of a heterogeneous group of tumors that are able to uptake neuroamine and/or specific receptors, such as somatostatin receptors, which can play important roles of the localization and treatment of these tumors. When considering therapy with radionuclides, the best radioligand should be carefully investigated. $^{131}I$-MIBG and beta-particle emitter labeled somatostatin analogs are well established radionuclide therapy modalities for NETs. $^{111}In,\;^{90}Y\;and\;^{177}Lu$ radiolabeled somatostatin analogues have been used for treatment of NETs. Further, radionuclide therapy modalities, for example, radioimmunotherapy, radiolabeled peptides such as minigastrin are currently under development and in different phases of clinical investigation. for all radionuclides used for therapy, long-term and survival statistics are not yet available and only partial tumour responses have been obtained using $^{131}I$-MIBG and $^{111}In$-octreotide. Experimental results using $^{90}Y$-DOTA-lanreotide as well as $^{90}Y-DOTA-D-Phe1-Tyr^3-octreotide$ and/or $^{177}Lu-DOTA-Tyr^3-octreotate$ have indicated the possible clinical potential of radionuclides receptor-targeted radiotherapy it may be hoped that the efficacy of radionuclide therapy will be improved by co-administration of chemotherapeutic drugs whose antitumoral properties may be synergistic with that of irradiation.

Convergence Analysis of LU Scheme for the Euler Equations on Unstructured Meshes

  • Kim Joo Sung;Kwon Oh Joon
    • 한국전산유체공학회:학술대회논문집
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    • 2003.10a
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    • pp.175-177
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    • 2003
  • The convergence characteristics of the LV scheme for the Euler equations have been investigated by using the Von Neumann stability analysis. The results indicated that the convergence rate is governed by a specific combination of CFD parameters. Based on this insight, it is shown that the convergence characteristics of the LV scheme is not deteriorated at any grid aspect-ratio as long as the local time step is defined based on the parameter combination. The numerical results demonstrated that this time step definition provide a uniform convergence for grid aspect-ratios between one to$1{\times}10^{4}$.

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PSMA Inhibitors for Nuclear Imaging and Radiotherapy of Prostate Cancer

  • Sajid Mushtaq;Tugsuu Uyanga;Park Ji Ae;Jung Young Kim
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.9 no.1
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    • pp.23-33
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    • 2023
  • Prostate cancer ranks as the world's second most frequently diagnosed cancer among men, and is responsible for the fifth highest number of cancer-related deaths in this population. The development of effective diagnostic and therapeutic approaches for prostate cancer remains a major challenge in the field of oncology. Over the past few years, the prostate-specific membrane antigen (PSMA) has raised as a hopeful tracer for the diagnosis and treatment of prostate cancer.Various radioisotopes, such as 131I, 99mTc, 68Ga, and 177Lu, have been used to label PSMA analogues, with varying degrees of success. Among these, 68Ga-PSMA-11 and 177Lu-PSMA-617 have emerged as the most promising radioligands for clinical use. Recently, researchers have been exploring the use of other radioisotopes, such as 211At, 89Zr, 64/67Cu, and 203/212Pb, for the labeling of PSMA-targeted radioligands. These radioisotopes have unique properties that may offer advantages over existing radioligands, such as longer half-lives, higher specific activities, and different emission profiles. Efforts are currently underway to develop these radiopharmaceuticals and make them more widely available for clinical use. These exciting developments highlight the potential of PSMA-targeted radioligands for the diagnosis and treatment of prostate cancer, and provided significant implications for the management of this disease in the future. The current study aims to provide a comprehensive summary of the latest research and clinical applications of radiolabeled PSMA inhibitors for diagnoses and therapy of prostate cancer, emphasizing the exciting developments in the field and their potential impact on clinical practice.

Tetrazolium Violet Induced Apoptosis and Cell Cycle Arrest in Human Lung Cancer A549 Cells

  • Zhang, Xiao-Hong;Zhang, Nan;Lu, Jian-Mei;Kong, Qing-Zhong;Zhao, Yun-Feng
    • Biomolecules & Therapeutics
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    • v.20 no.2
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    • pp.177-182
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    • 2012
  • Tetrazolium violet is a tetrazolium salt and has been proposed as an antitumor agent. In this study, we reported for the first time that tetrazolium violet not only inhibited human lung cancer A549 cell proliferation but also induced apoptosis and blocked cell cycle progression in the G1 phase. The results showed that tetrazolium violet significantly decreased the viability of A549 cells at $5-15{\mu}M$. Tetrazolium violet -induced apoptosis in A549 cells was confirmed by H33258 staining assay. In A549, tetrazolium violet blocked the progression of the cell cycle at G1 phase by inducing p53 expression and further up-regulating p21/WAF1 expression. In addition, an enhancement in Fas/APO-1 and its two forms of ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), as well as caspase, were responsible for the apoptotic effect induced by tetrazolium violet. The conclusion of this study is that tetrazolium violet induced p53 expression which caused cell cycle arrest and apoptosis. These findings suggest that tetrazolium violet has strong potential for development as an agent for treatment lung cancer.