Cyclotrons

回旋加速器
  • 文章类型: Journal Article
    Chulabhorn医院的国家回旋加速器和PET中心使用最先进的数字PET/CT和PET/MRI机器以及其他相关设备提供核医学诊断服务。此外,该中心通过拥有回旋加速器来生产放射性药物而发挥着至关重要的作用,在国内和全国其他医院都使用。尽管该中心严格遵守有关患者使用放射性物质的国际标准,操作人员仍然存在辐射暴露的潜在风险,工人,和公众由于放射性污染和非密封来源的排放。因此,必须评估和持续监测工作区域的辐射水平,以确保人员的最高安全水平。方法:本研究使用光学激发发光剂量计测量17个地区的辐射水平,由9个控制区域和8个监督区域组成。在3个月的时间里,记录每个地点的平均每月辐射剂量.结果:PET/CT室记录了受控区域内最高的辐射剂量,月平均1.81±0.29mSv,相当于21.72mSv的年剂量。这种较高的剂量可以归因于在这个房间中服务的大量患者。在监督区域,位于检查室和患者等候区之间的护理柜台显示出最高的辐射暴露。在该位置测量的平均每月剂量为0.085±0.019mSv,导致1.015mSv的年剂量。结论:对受控和监督区域的辐射剂量的评估表明,总体辐射水平保持在规定的范围内。然而,在护理柜台观察到的轻微超标表明需要改进,以确保符合合理可实现的低至低原则.应每年对辐射水平进行持续监测,以保持安全标准,并尽量减少工人和公众接触放射性的风险。
    The National Cyclotron and PET Centre at Chulabhorn Hospital offers nuclear medicine diagnostic services using state-of-the-art digital PET/CT and PET/MRI machines as well as other related devices. Additionally, the center plays a vital role by having a cyclotron to produce radiopharmaceuticals, which are used both in-house and in other hospitals throughout the country. Despite the center\'s strict adherence to international standards regarding the use of radioactive substances in patients, there remains a potential risk of radiation exposure for operators, workers, and the public due to radioactive contamination and emissions from unsealed sources. Hence, it is imperative to assess and continuously monitor radiation levels in the work area to ensure the utmost level of safety for personnel. Methods: This study used optically stimulated luminescence dosimeters to measure radiation levels in 17 areas, consisting of 9 controlled and 8 supervised areas. Over a 3-mo period, the average monthly radiation dose was recorded for each location. Results: The PET/CT room registered the highest radiation dose within the controlled area, with a monthly average of 1.81 ± 0.29 mSv, equivalent to an annual dose of 21.72 mSv. This higher dose can be attributed to the significant number of patients served in this room. In supervised areas, the nursing counter located between the examination room and the patient waiting area exhibited the highest radiation exposure. The average monthly dose measured at this location was 0.085 ± 0.019 mSv, resulting in an annual dose of 1.015 mSv. Conclusion: The evaluation of radiation dose in controlled and supervised areas indicated that the overall radiation level remains within the prescribed limits. However, the slight excess that was observed at the nursing counter indicates the need for improvement to ensure compliance with the as-low-as-reasonably-achievable principle. Continuous monitoring of radiation levels should be conducted annually to maintain safety standards and minimize the risk that workers and the general public will be exposed to radioactivity.
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  • 文章类型: Journal Article
    在具有放射性物质和高能回旋加速器束的实验室中,对电离辐射的防护非常重要。位于宫城县东北大学的回旋加速器和放射性同位素中心(CYRIC),日本是著名的核科学实验室,拥有回旋加速器束和大量高活性放射性物质。考虑到这一点,重要的是要进行完整的辐射传输计算,以确保非职业和职业工人的安全。在目前的工作中,我们已经建立了一个完整的三维模型的主回旋加速器建筑和辐射实验室使用蒙特卡罗方法。我们发现,CYRIC建筑物内部和周围的分散光子和中子对职业和非职业工人没有重大风险。目前的工作和开发的模型将在辐射防护领域有用。
    Protection against ionizing radiations is important in laboratories with radioactive materials and high energy cyclotron beams. The Cyclotron and Radioisotope Center (CYRIC) located in Tohoku University in Miyagi prefecture, Japan and is a well-known nuclear science laboratory with cyclotron beams and substantial number of high activity radioactive materials. Considering this, it is important to perform complete radiation transport computations to ensure the safety of non-occupational and occupational workers. In the present work, we have developed a complete 3-dimensional model of the main cyclotron building and radiation labs using Monte Carlo method. We have found that the dispersed photons and neutrons inside and in the surrounding of the CYRIC building pose no significant risk to occupational and non-occupational workers. The present work and the developed models would be useful in the field of radiation protection.
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  • 文章类型: Journal Article
    背景:具有高空间和时间分辨率的剂量计对于笔形束扫描(PBS)质子束表征将具有重要意义,特别是当面对具有高时间动态的小场和光束时。当成像系统能够与光束产生加速器同步操作时,闪烁体的光学成像具有提供具有逐脉冲基础时间分辨率的亚毫米空间分辨率的潜力。
    目的:我们证明了对PBS质子束进行成像的可行性,因为它们穿过塑料闪烁体探测器以同时获得多个束参数,包括质子范围,笔形光束在不同深度的宽度,现货的尺寸,以及以亚毫米分辨率逐脉冲为基础的光斑位置。
    方法:使用PBS同步回旋加速器进行质子辐照。BC-408塑料闪烁体模块,尺寸为30×30×5cm3,和另一块30×30×0.5cm3大小,定位在一个光学密封的外壳,依次用于测量质子范围,和斑点大小/位置,分别。使用通过门控模块与加速器脉冲同步的高速互补金属氧化物半导体(CMOS)相机系统进行成像。闪烁图像,用相机直接面对5厘米厚的闪烁体捕获,对背景(BG)进行了校正,和闪烁体的电离猝灭以获得质子范围。当使用45°镜将闪烁光反射向相机时,从0.5cm厚的闪烁体的闪烁图像中获得斑点的位置和大小。
    结果:捕获了对应于所有质子脉冲的0.16mm/像素分辨率的闪烁图像。逐脉冲分析表明,范围的变化,斑点\'位置,和尺寸在其平均值的±0.2%标准偏差内。绝对范围在其预期值的±1mm内。平均斑点位置大多在±0.8mm内,并且斑点\'sigma在预期值的0.2mm内一致。
    结论:具有高时空分辨率的闪烁成像PBS光束是可行的,可能有助于对现有甚至新兴技术(如FLASH)进行有效且具有成本效益的验收测试和调试,网格,迷你横梁,等等。
    BACKGROUND: A dosimeter with high spatial and temporal resolution would be of significant interest for pencil beam scanning (PBS) proton beams\' characterization, especially when facing small fields and beams with high temporal dynamics. Optical imaging of scintillators has potential in providing sub-millimeter spatial resolution with pulse-by-pulse basis temporal resolution when the imaging system is capable of operating in synchrony with the beam-producing accelerator.
    OBJECTIVE: We demonstrate the feasibility of imaging PBS proton beams as they pass through a plastic scintillator detector to simultaneously obtain multiple beam parameters, including proton range, pencil beam\'s widths at different depths, spot\'s size, and spot\'s position on a pulse-by-pulse basis with sub-millimeter resolution.
    METHODS: A PBS synchrocyclotron was used for proton irradiation. A BC-408 plastic scintillator block with 30 × 30 × 5 cm3 size, and another block with 30 × 30 × 0.5 cm3 size, positioned in an optically sealed housing, were used sequentially to measure the proton range, and spot size/location, respectively. A high-speed complementary metal-oxide-semiconductor (CMOS) camera system synchronized with the accelerator\'s pulses through a gating module was used for imaging. Scintillation images, captured with the camera directly facing the 5-cm-thick scintillator, were corrected for background (BG), and ionization quenching of the scintillator to obtain the proton range. Spots\' position and size were obtained from scintillation images of the 0.5-cm-thick scintillator when a 45° mirror was used to reflect the scintillation light toward the camera.
    RESULTS: Scintillation images with 0.16 mm/pixel resolution corresponding to all proton pulses were captured. Pulse-by-pulse analysis showed that variations of the range, spots\' position, and size were within ± 0.2% standard deviation of their average values. The absolute ranges were within ± 1 mm of their expected values. The average spot-positions were mostly within ± 0.8 mm and spots\' sigma agreed within 0.2 mm of the expected values.
    CONCLUSIONS: Scintillation-imaging PBS beams with high-spatiotemporal resolution is feasible and may help in efficient and cost-effective acceptance testing and commissioning of existing and even emerging technologies such as FLASH, grid, mini-beams, and so forth.
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  • 文章类型: Journal Article
    糖基化是生物体中常见的修饰,在理解生物系统和疾病中起着核心作用。在过去的几十年中,我们探测gylcome的能力呈指数级增长。然而,对研究人员可用的分析工具箱的进一步改进将允许增强探测生物系统的结构和功能以及改善疾病治疗的能力。本文将二维傅立叶变换离子回旋共振质谱技术应用于标准糖蛋白珊瑚树凝集素(CTL)和牛核糖核酸酶B(BRB)的糖蛋白质组学工作流程,以证明其作为糖蛋白质组学工作流程工具的可行性。CTL的2D红外多光子解离和电子捕获解离光谱揭示了与其1D对应物相当的结构信息,确认聚糖的糖基化位点和单糖组成。在BRB的2D中收集的光谱揭示了使用红外多光子解离收集的数据的碎片离子扫描和垂直前体离子扫描的相关线,以及通过电子捕获解离收集的数据的对角分裂线。在不希望色谱分离或四极杆分离不充分的情况下,使用类似的技术进行糖蛋白质组分析可能证明是有价值的。
    Glycosylation is a common modification across living organisms and plays a central role in understanding biological systems and disease. Our ability to probe the gylcome has grown exponentially in the past several decades. However, further improvements to the analytical toolbox available to researchers would allow for increased capabilities to probe structure and function of biological systems and to improve disease treatment. This article applies the developing technique of two-dimensional Fourier transform ion cyclotron resonance mass spectrometry to a glycoproteomic workflow for the standard glycoproteins coral tree lectin (CTL) and bovine ribonuclease B (BRB) to demonstrate its feasibility as a tool for glycoproteomic workflows. 2D infrared multiphoton dissociation and electron capture dissociation spectra of CTL reveal comparable structural information to their 1D counterparts, confirming the site of glycosylation and monosaccharide composition of the glycan. Spectra collected in 2D of BRB reveal correlation lines of fragment ion scans and vertical precursor ion scans for data collected using infrared multiphoton dissociation and diagonal cleavage lines for data collected by electron capture dissociation. The use of similar techniques for glycoproteomic analysis may prove valuable in instances where chromatographic separation is undesirable or quadrupole isolation is insufficient.
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  • 文章类型: Journal Article
    具有2-氟-2-脱氧-D-葡萄糖(FDG)的正电子发射断层扫描(PET)成像在癌症患者的诊断和管理中的作用已得到充分确立。随着PET成像需求的不断上升,许多医院正在安装现场自屏蔽微型回旋加速器,以生产自己的放射性药物,包括FDG。2021年5月,按需剂量生物标志物发生器(BG-75)安装在希腊的Metaxa癌症医院,使其成为全国第一家基于医院的PET放射性药物回旋加速器。调试期间,确定了人员的预期外部风险,发现内部暴露可以忽略不计。使用两种方法估算人员剂量:不同位置的测量仪表测量值以及在每个位置花费的时间,和使用电子个人剂量计直接测量。回旋加速器拱顶外的伽马和中子辐射读数处于背景水平。在回旋加速器拱顶内,目标记录的最高读数为γ和中子均为18μSv/h;在一米处,值分别为5μSv/h和4μSv/h,分别。基于这些测量,每个操作员的年度预期全身剂量为0.6mSv,并且相应的肢体剂量是16mSv。放射化学家的全年预期全身和四肢剂量为0.3mSv和25mSv,分别。医学物理学家的预期剂量估计也低于1mSv。这些剂量远低于监管限制和当地低至合理可实现(ALARA)水平。凭借经验和强大的ALARA程序,人员暴露可以进一步减少。 .
    The role of18F-fluoro-deoxy-glucose in positron emission tomography (PET) imaging is well established in diagnosis and management of cancer patients. Installations of on-site self-shielded mini cyclotrons are increasing. The Dose on Demand Biomarker Generator BG-75 was installed at Metaxa Cancer Hospital, Greece, in May 2021 and is the first hospital-based PET radiopharmaceutical cyclotron in the country. Personnel expected external exposure was established during commissioning; internal exposure is not expected. Personnel dose was estimated with two methods: survey meter measurements in various locations combined with the time spent in each location, and direct measurement using electronic personal dosemeters. Gamma and neutron radiation readings outside the cyclotron vault were at background levels. Inside the cyclotron vault, the highest recorded radiation readings by the target were 18μSv h-1for both gammas and neutrons with cyclotron in operational mode; at one meter, the values were 5μSv h-1and 4μSv h-1, respectively. The annual expected whole body dose per cyclotron operator is 0.6 mSv, and the respective extremity dose 16 mSv. The annual expected whole body and extremity dose for the radiochemist is 0.3 mSv and 25 mSv, respectively. The respective annual dose estimates for the medical physicists are < 1 mSv. The expected personnel doses are well below the regulatory limits and local as low as reasonably achievable (ALARA) levels. With experience and a robust ALARA program, personnel exposure could be further reduced.
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  • 文章类型: Journal Article
    背景:已知用于移动目标的铅笔束扫描(PBS)质子治疗受到扫描束和器官运动之间的相互作用效应的影响。虽然胸部区域的呼吸运动是器官运动的主要原因,相互作用效应取决于质子加速器的输送特性。
    目的:为了评估不同类型的PBS质子加速器和光斑尺寸对相互作用效应的影响,缓解措施,和计划质量的立体定向身体放射治疗(SBRT)治疗非小细胞肺癌(NSCLC)。
    方法:选择20例接受光子SBRT治疗的非小细胞肺癌患者进行回顾性研究,以代表不同的肿瘤体积和呼吸运动幅度(中位:0.6cm,腹部压迫)。对于每个病人来说,使用以下方法创建计划:(1)回旋加速器产生的质子束(CPB),光斑尺寸为σ=2.7-7.0mm;(2)线性加速器质子束(LPB)(σ=2.9-5.5mm);(3)线性加速器质子小束(LPMB)(σ=0.9-3.9mm)。CPB的能量切换时间为1秒,LPMB和LPB为0.005s。使用四维计算机断层扫描(4DCT)扫描的每个单独阶段,在总肿瘤体积(GTV)上对计划进行了稳健优化。最初,对单场优化(SFO)计划进行了评估;如果计划质量不符合剂量测定要求,使用多场优化(MFO)。为所有患者创建MFO计划用于比较。对于每个病人来说,所有计划均正常化,99%的GTV接受相同剂量.通过计算10个呼吸阶段的剂量来评估相互作用效应,基于现货分布。每个计划进行2-6次体积重涂(VR)。我们比较了接受100%的GTV处方剂量(V100%RX)的体积,和正常肺V20Gy。
    结果:使用SFO可以充分优化20个计划中的12个。就LPB和LPMB的目标覆盖率而言,与MFO计划相比,SFO计划对相互作用效应的敏感性较低。以下比较显示了利用MFO技术的结果。在不重新绘画的相互作用评估中,GTV的平均V100%RX为99.42±0.6%,97.52±3.9%,CPB为94.49±7.3%,LPB,和LPMB计划,分别。在VR之后(CPB为2倍;LPB为3倍;LPMB为5倍),GTV的V100%RX(平均)提高了0.13%,1.84%,和4.63%,分别,达到V100%RX>95%的验收标准。由于线性加速器质子机器的快速能量切换,VR计划的交付时间是LPB计划的最低时间,而LPMB的分娩时间平均比CPB计划长1分钟。小斑点机的优点是在正常肺V20Gy中更好地保留,即使是在VR应用的时候。
    结论:在没有重新粉刷的情况下,具有大光斑尺寸的质子机器产生了更强大的对抗相互作用效应的计划。VR的数量随着光斑尺寸的减小而增加,以达到验收标准。对于具有小光斑尺寸和快速能量变化的模态,VR提高了针对相互作用效应的计划鲁棒性。保留LPMB的低剂量保留方面,即使包括运动。
    BACKGROUND: Pencil beam scanning (PBS) proton therapy for moving targets is known to be impacted by interplay effects between the scanning beam and organ motion. While respiratory motion in the thoracic region is the major cause for organ motion, interplay effects depend on the delivery characteristics of proton accelerators.
    OBJECTIVE: To evaluate the impact of different types of PBS proton accelerators and spot sizes on interplay effects, mitigations, and plan quality for Stereotactic Body Radiation Therapy (SBRT) treatment of non-small cell lung cancer (NSCLC).
    METHODS: Twenty NSCLC patients treated with photon SBRT were selected to represent varying tumor volumes and respiratory motion amplitudes (median: 0.6 cm with abdominal compression) for this retrospective study. For each patient, plans were created using: (1) cyclotron-generated proton beams (CPB) with spot sizes of σ = 2.7-7.0 mm; (2) linear accelerator proton beams (LPB) (σ = 2.9-5.5 mm); and (3) linear accelerator proton minibeams (LPMB) (σ = 0.9-3.9 mm). The energy switching time is one second for CPB, and 0.005 s for LPMB and LPB. Plans were robustly optimized on the gross tumor volume (GTV) using each individual phase of four-dimensional computed tomography (4DCT) scans. Initially, single-field optimization (SFO) plans were evaluated; if the plan quality did not meet the dosimetric requirement, multi-field optimization (MFO) was used. MFO plans were created for all patients for comparisons. For each patient, all plans were normalized to have the same dose received by 99% of the GTV. Interplay effects were evaluated by computing the dose on 10 breathing phases, based on the spot distribution. Volumetric repainting (VR) was performed 2-6 times for each plan. We compared volume receiving 100% of the prescribed dose (V100%RX) of the GTV, and normal lung V20Gy.
    RESULTS: Twelve of 20 plans can be optimized sufficiently with SFO. SFO plans were less sensitive to the interplay effect compared to MFO plans in terms of target coverage for both LPB and LPMB. The following comparisons showed results utilizing the MFO technique. In the interplay evaluation without repainting, the mean V100%RX of the GTV were 99.42 ± 0.6%, 97.52 ± 3.9%, and 94.49 ± 7.3% for CPB, LPB, and LPMB plans, respectively. Following VR (2 × for CPB; 3 × for LPB; 5 × for LPMB), V100%RX of the GTV were improved (on average) by 0.13%, 1.84%, and 4.63%, respectively, achieving the acceptance criteria of V100%RX > 95%. Because of fast energy switch in linear accelerator proton machines, the delivery time for VR plans was the lowest for LPB plans, while delivery time for LPMB was on average 1 min longer than CPB plans. The advantage of small spot machines was better sparing in normal lung V20Gy, even when VR was applied.
    CONCLUSIONS: In the absence of repainting, proton machines with large spot sizes generated more robust plans against interplay effects. The number of VR increased with decreasing spot sizes to achieve the acceptance criteria. VR improved the plan robustness against interplay effects for modalities with small spot sizes and fast energy changes, preserving the low dose sparing aspect of the LPMB, even when motion is included.
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  • 文章类型: Journal Article
    采用粒子编码的电子回旋共振加热方法分析加热现象,轴向动能,以及由氢气和氦气背景气体在ELTRAP装置中限制电子等离子体的自洽电场。电磁模拟是在3.8V的恒定功率下进行的,适用于不同的RF驱动器(0.5GHz-8GHz),以及1GHz恒定频率在这些变化的幅度(1V-3.8V)。与两种背景气体的其他振幅和频率相比,轴向和径向温度的影响在1.8V和5GHz处最大。由于更多的电离和二次电子的产生,这些影响在不同的射频下更高,氢背景气体的最大记录径向温度为170.41eV。由于通过C8电极施加的VRF,发现轴向动能冲击在ELTRAP装置的外径向部分(0.03和0.04米之间)中更有效。在5GHzRF下,氦气背景气体的自洽电场高于其他振幅和射频。与氢气背景气体相比,氦气背景气体中的激发和电离速率沿径向方向(r轴)高于轴向方向(z轴)。目前的研究有利于核物理应用,光束物理,微电子,相干辐射装置和磁控管。
    Electron cyclotron resonance heating method of Particle-in-Cell code was used to analyze heating phenomena, axial kinetic energy, and self-consistent electric field of confined electron plasma in ELTRAP device by hydrogen and helium background gases. The electromagnetic simulations were performed at a constant power of 3.8 V for different RF drives (0.5 GHz- 8 GHz), as well as for 1 GHz constant frequency at these varying amplitudes (1 V-3.8 V). The impacts of axial and radial temperatures were found maximum at 1.8 V and 5 GHz as compared to other amplitudes and frequencies for both background gases. These effects are higher at varying radio frequencies due to more ionization and secondary electrons production and maximum recorded radial temperature for hydrogen background gas was 170.41 eV. The axial kinetic energy impacts were found more effective in the outer radial part (between 0.03 and 0.04 meters) of the ELTRAP device due to applied VRF through C8 electrode. The self-consistent electric field was found higher for helium background gas at 5 GHz RF than other amplitudes and radio frequencies. The excitation and ionization rates were found to be higher along the radial direction (r-axis) than the axial direction (z-axis) in helium background gas as compared to hydrogen background gas. The current studies are advantageous for nuclear physics applications, beam physics, microelectronics, coherent radiation devices and also in magnetrons.
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  • 文章类型: Journal Article
    木质素是一种复杂的杂芳族聚合物,是地球上最丰富和多样化的生物聚合物之一。它约占所有木本植物物质的三分之一,使其成为一个有吸引力的候选人,石化产品的可再生原料,用于生产精细化学品。然而,木质素的固有复杂性使得使用常见的分析技术进行分析和表征变得困难,证明阻碍了木质素作为绿色化学原料的利用。在这里,我们概述了使用傅里叶变换离子回旋共振质谱(FT-ICRMS)的组合化学分析方法以半定量方式跟踪亲碱漆酶对木质素的降解,以表征化学多样性和离子相对丰度的变化。和核磁共振来突出木质素结构的变化。具体来说,一种嗜碱性漆酶被用来降解工业相关的木质素,治疗24小时后,几乎完全除去了化合物如丁香草素(95%)。结构分析加强了这些发现,表明与β-β键相关的NMR信号损失>50%,其中丁香加瑞辛醇是代表。最终,这项工作强调了一种组合的分析方法,可用于获得对复合物内漆酶酶活性的更广泛的半定量理解,非模型混合物。
    Lignin is a complex heteroaromatic polymer which is one of the most abundant and diverse biopolymers on the planet. It comprises approximately one third of all woody plant matter, making it an attractive candidate as an alternative, renewable feedstock to petrochemicals to produce fine chemicals. However, the inherent complexity of lignin makes it difficult to analyse and characterise using common analytical techniques, proving a hindrance to the utilisation of lignin as a green chemical feedstock. Herein we outline the tracking of lignin degradation by an alkaliphilic laccase in a semi-quantitative manner using a combined chemical analysis approach using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to characterise shifts in chemical diversity and relative abundance of ions, and NMR to highlight changes in the structure of lignin. Specifically, an alkaliphilic laccase was used to degrade an industrially relevant lignin, with compounds such as syringaresinol being almost wholly removed (95%) after 24 hours of treatment. Structural analyses reinforced these findings, indicating a >50% loss of NMR signal relating to β-β linkages, of which syringaresinol is representative. Ultimately, this work underlines a combined analytical approach that can be used to gain a broader semi-quantitative understanding of the enzymatic activity of laccases within a complex, non-model mixture.
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  • 文章类型: Journal Article
    背景:对NetSpot和Illuccix的需求增加,作为接受Lutathera和Pluvicto放射治疗的要求,并监测后续的治疗反应,加强了开发生产镓-68(68Ga)的替代方法的需求。基于我们在GEPETtrace上的液体目标中生产68Ga的努力,这项工作的目的是使用FASTLab2合成模块修改当前的GE氯化镓盒,以生产相当于1.85GBq发生器的[68Ga]GaCl3,并证明与FDA批准的用于生产68Ga标记的放射性药物的试剂盒的兼容性。
    方法:68Ga是通过68Zn在液体靶中产生的(p,n)68Ga反应。68Ga加载到各种尺寸的ZR树脂上(ZR加载,0.3mL,1mL,或2毫升)。使用剂量校准器确定加载效率。用HNO3洗涤后,使用1.75MHCl通过各种尺寸的第二种ZR树脂(ZRCG,0mL,2mL,4mL)。使用0.5mL馏分,确定洗脱曲线。研究了[68Ga]GaCl3与NetSpot和Illuccix试剂盒的相容性。使用放射性TLC和放射性HPLC测定放射化学纯度(RCP)和4小时稳定性。使用改进的[68Ga]GaCl3盒和新的FASTLab程序,使用NetSpot和Illuccix试剂盒进行了6种验证准备,其中RCP,稳定性,确定了不育和适宜性。还进行了2个液体靶的双重辐照,通过用0.1MHCl稀释所需的活性,用于同时制备1个NetSpot和2个Illuccix试剂盒。
    结果:市售的GE盒使用市售的FDA试剂盒给出低RCP。为了优化这个,对ZR负载的负载效率和用于负载初始活性和随后洗脱的ZR树脂的比率进行了探索。当使用ZR负载与ZRCG的2:4比率时,当使用3.8mL[68Ga]GaCl3溶液时,观察到97.89%RCP。对于Dotatate验证,将0.55mL缓冲液加入到4.2mL的[68Ga]GaCl3中,得到1.35GBq的配制产物。对于Illuccix验证,将[68Ga]GaCl3加入2.5mL缓冲液中,得到1.52GBq的[68Ga]Ga-PSMA-11。配方产品通过包装插入质量控制(QC)要求。当进行双目标照射时,2.84GBq被送到外部小瓶中,并用于同时标记1个NetSpot和2个Illuccix套件,每个试剂盒也符合或超过既定的QC标准。
    结论:报道了使用回旋加速器从液体靶标产生的68Ga与FDA批准的NetSpot和Illucix试剂盒结合使用的方法。通过使用2mLZRLoad树脂和4mLZRCG树脂,在残余68Zn和期望的68Ga之间实现足够的分辨率。通过修改FASTLab程序以保留来自ZRCG树脂的最终2.5mL洗脱液,获得了相当于新的1.85GBq发生器的[68Ga]GaCl3。这适用于标记NetSpot和Illucix套件,导致68Ga的高掺入(RCP>95%),这一点以前没有得到证实。将[68Ga]GaCl3递送到外部小瓶中并用0.1MHCl稀释使得可以同时制备多个试剂盒。这些新程序应有助于将回旋加速器产生的[68Ga]GaCl3用于临床生产。
    Increased demand for NetSpot and Illuccix as requirement to receive the respective Lutathera and Pluvicto radiotherapies, and monitor subsequent response to treatment, have reinforced the need to develop alternative ways of producing gallium-68 (68Ga). Building on our efforts to produce 68Ga in a liquid target on a GE PETtrace, the goal of this work is to modify the current GE Gallium Chloride cassette using the FASTLab 2 synthesis module to produce [68Ga]GaCl3 equivalent to a 1.85 GBq generator and demonstrate compatibility with FDA-approved kits for production of 68Ga-labeled radiopharmaceuticals.
    68Ga was produced in a liquid target via the 68Zn(p,n)68Ga reaction. 68Ga was loaded onto various sizes of ZR resins (ZR Load, 0.3 mL, 1 mL, or 2 mL). The loading efficiency was determined using a dose calibrator. After washing with HNO3, 1.75 M HCl was used to elute the ZR Load resin through various sizes of a second ZR resin (ZR CG, 0 mL, 2 mL, 4 mL). Using 0.5 mL fractions, the elution profile was determined. Compatibility of the [68Ga]GaCl3 with NetSpot and Illuccix kits was investigated. Radiochemical purity (RCP) and 4 h stability were determined using radioTLC and radioHPLC. Using a modified [68Ga]GaCl3 cassette and new FASTLab program, 6 validation preparations were conducted using NetSpot and Illuccix kits for which RCP, stability, sterility and suitability were determined. Dual irradiation of 2 liquid targets was also performed, which was used to simultaneously prepare 1 NetSpot and 2 Illuccix kits by diluting the required activity with 0.1 M HCl.
    The commercially available GE Cassette gave low RCP using commercial FDA kits. To optimize this, the loading efficiency onto ZR Load and the ratio of ZR resin used to load the initial activity and subsequent elution were explored. When using a 2:4 ratio of ZR Load to ZR CG, 97.89 % RCP was observed when a 3.8 mL [68Ga]GaCl3 solution was used. For Dotatate validation, 0.55 mL of buffer was added to 4.2 mL of [68Ga]GaCl3 which gave 1.35 GBq of formulated product. For Illuccix validation, [68Ga]GaCl3 was added to 2.5 mL of buffer which gave 1.52 GBq of [68Ga]Ga-PSMA-11. Formulated products passed package insert quality control (QC) requirements. When dual target irradiations were performed, 2.84 GBq was delivered to an external vial and used to label 1 NetSpot and 2 Illuccix kits simultaneously, and each kit also met or exceeded established QC criteria.
    Methods are reported for using cyclotron-produced 68Ga from a liquid target in conjunction with FDA-approved NetSpot and Illucix kits. By employing a 2 mL ZR Load resin with a 4 mL ZR CG resin, adequate resolution between residual 68Zn and desired 68Ga was achieved. By modifying the FASTLab procedure to retain the final 2.5 mL of eluate from the ZR CG resin, [68Ga]GaCl3 equivalent to a new 1.85 GBq generator was obtained. This was suitable for labeling NetSpot and Illucix kits, resulting in high incorporation of 68Ga (RCP >95 %), which has not previously been demonstrated. Delivering [68Ga]GaCl3 into an external vial and diluting with 0.1 M HCl makes it possible to prepare multiple kits simultaneously. These new procedures should facilitate use of cyclotron-produced [68Ga]GaCl3 for clinical production going.
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  • 文章类型: Journal Article
    在各种严格条件下,钴-石锅配合物表现出高动力学惰性,但是关于放射性标记和体内正电子发射断层扫描(PET)成像的文献有限,没有添加55Co的载体。为了填补这个空白,本研究首先研究了用55Co对DiAmSar(DSar)的放射性标记,随后在人血清和EDTA中进行稳定性评估,在小鼠体内的药代动力学,并与[55Co]CoCl2进行直接比较,以评估药代动力学差异。此外,放射性标记方法成功地用于产生NTSR1靶向的PET剂[55Co]Co-NT-Sarcage(DSar功能化的SR142948衍生物),并给予HT29肿瘤异种移植小鼠.[55Co]Co-DSar复合物可以在37°C下形成,其纯度和稳定性适合临床前体内放射性药物应用,和[55Co]Co-NT-Sarcage表现出突出的肿瘤摄取,背景信号低。与[64Cu]Cu-NT-讽刺直接比较,[55Co]Co-NT-Sarcage实现了更高的肿瘤与肝脏的比率,但具有总体相似的生物分布特征。这些结果表明,Sar将是用于构建Co基放射性药物(包括用于PET的55Co和用于治疗应用的58mCo)的有前途的螯合剂。
    Cobalt-sarcophagine complexes exhibit high kinetic inertness under various stringent conditions, but there is limited literature on radiolabeling and in vivo positron emission tomography (PET) imaging using no carrier added 55Co. To fill this gap, this study first investigates the radiolabeling of DiAmSar (DSar) with 55Co, followed by stability evaluation in human serum and EDTA, pharmacokinetics in mice, and a direct comparison with [55Co]CoCl2 to assess differences in pharmacokinetics. Furthermore, the radiolabeling process was successfully used to generate the NTSR1-targeted PET agent [55Co]Co-NT-Sarcage (a DSar-functionalized SR142948 derivative) and administered to HT29 tumor xenografted mice. The [55Co]Co-DSar complex can be formed at 37 °C with purity and stability suitable for preclinical in vivo radiopharmaceutical applications, and [55Co]Co-NT-Sarcage demonstrated prominent tumor uptake with a low background signal. In a direct comparison with [64Cu]Cu-NT-Sarcage, [55Co]Co-NT-Sarcage achieved a higher tumor-to-liver ratio but with overall similar biodistribution profile. These results demonstrate that Sar would be a promising chelator for constructing Co-based radiopharmaceuticals including 55Co for PET and 58mCo for therapeutic applications.
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