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Preclinical Aspects of [89Zr]Zr-DFO-Rituximab: A High Potential Agent for Immuno-PET Imaging. 89Zr]Zr-DFO-利妥昔单抗的临床前研究:一种极具潜力的免疫 PET 成像剂。
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-24 DOI: 10.2174/0118744710326742241018050220
Zahra Rouhollahi, Seyed Mahmoud Reza Aghamiri, Hassan Yousefnia, Behrouz Alirezapour, Ali Moghaddasi, Samaneh Zolghadri

Background: An early diagnosis of cancer can lead to choosing more effective treatment and increase the number of cancer survivors. In this study, the preparation and preclinical aspects of [89Zr]Zr-DFO-Rituximab, a high-potential agent for PET imaging of Non- Hodgkin Lymphoma (NHL), were evaluated.

Methods: DFO was conjugated to rituximab monoclonal antibody (mAb), and DFO-rituximab was successfully labeled with zirconium-89 (89Zr) at optimized conditions. The stability of the complex was assessed in human blood serum and PBS buffer. Radioimmunoreactivity (RIA) of the radioimmunoconjugate (RIC) was evaluated on CD20-overexpressing Raji cell line and CHO cells. The biodistribution of the radiolabeled mAb was studied in normal and tumorbearing rodents. Finally, the absorbed dose in human organs was estimated.

Results: The radiolabeled compound was prepared with radiochemical purity (RCP) >99% (RTLC) and a specific activity of 180±1.8 GBq/g. The RCP of the final complex PBS buffer and human blood serum was higher than 95%, even after 48 h post incubation. The RIA assay demonstrated that more than 63% of the radiolabeled compound (40 ng/ml, 0.5 mL) was bound to 5×106 Raji cells. The biodistribution of the final product in tumor-bearing mice showed a high accumulation of the RIC in the tumor site in all intervals post-injection. Tumor/ non-target ratios were increased over time, and longer imaging time was suggested. The dosimetry data indicated that the liver received the most absorbed dose after the complex injection.

Conclusion: [89Zr]Zr-DFO-Rituximab represents a significant advancement in the field of oncological imaging and offers a robust platform for both diagnostic and therapeutic applications in the management of B-cell malignancies.

背景:癌症的早期诊断可以帮助人们选择更有效的治疗方法,并增加癌症幸存者的数量。本研究对[89Zr]Zr-DFO-利妥昔单抗的制备和临床前方面进行了评估:方法:将DFO与利妥昔单抗(mAb)共轭,并在优化条件下用锆-89(89Zr)成功标记了DFO-利妥昔单抗。评估了复合物在人血清和 PBS 缓冲液中的稳定性。在表达 CD20 的 Raji 细胞系和 CHO 细胞上评估了放射免疫结合剂(RIC)的放射免疫反应性(RIA)。研究了放射性标记 mAb 在正常啮齿动物和肿瘤啮齿动物中的生物分布。最后,估算了人体器官的吸收剂量:结果:制备的放射性标记化合物的放射化学纯度(RCP)大于 99%(RTLC),比活度为 180±1.8 GBq/g。最终复合物 PBS 缓冲液和人血清的 RCP 值高于 95%,即使在培养 48 小时后也是如此。RIA 检测表明,超过 63% 的放射性标记化合物(40 纳克/毫升,0.5 毫升)与 5×106 个 Raji 细胞结合。最终产品在肿瘤小鼠体内的生物分布显示,在注射后的所有时间间隔内,RIC 在肿瘤部位都有大量积累。随着时间的推移,肿瘤/非靶标比率增加,建议延长成像时间。剂量测定数据表明,复合注射后肝脏吸收的剂量最大:结论:[89Zr]Zr-DFO-利妥昔单抗代表了肿瘤成像领域的一大进步,为B细胞恶性肿瘤的诊断和治疗应用提供了一个强大的平台。
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引用次数: 0
Enhancing Ketoprofen Solubility: A Strategic Approach Using Solid Dispersion and Response Surface Methodology. 提高酮洛芬的溶解度:使用固体分散和响应面方法的战略方法。
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-24 DOI: 10.2174/0118744710311951241018054453
Devika Tripathi, Dinesh Kumar Sharma, Jagannath Sahoo
<p><strong>Background: </strong>In the pharmaceutical sciences, the solubility profile of therapeutic molecules is crucial for identifying and formulating drugs and evaluating their quality across the drug discovery pipeline based on factors like oral bioavailability, metabolic transformation, biodistribution kinetics, and potential toxicological implications. The investigation aims to enhance the solubility parameters of ketoprofen (BCS-II class), which exhibits low solubility and high permeability.</p><p><strong>Methods: </strong>In this method, hydrotrope blends of aromatic sodium benzoate and electrolyte sodium acetate were employed to enhance the solubility parameter of ketoprofen. Several batches of solid dispersion of ketoprofen were made using a solvent evaporation method, and the response surface method 3² factorial design was used to find the best one. The optimised formulation, KSD9, underwent in-vitro drug dissolution, DSC, pXRD, and SEM studies.</p><p><strong>Results: </strong>The optimized batch demonstrated substantial improvement in ketoprofen solubility, attributed to mixed hydrotropy. The results indicated that both solubility and %CDR improved when hydrotropes were employed, suggesting a direct proportionality between the rise in solubility and %CDR. Formulations KSD1-KSD9 exhibited solubility enhancements ranging from 2.23 to 5.77-fold, along with an elevation in %CDR from 72.28% to 94.76%. This implies that the %CDR was modulated by the hydrotropes, specifically influenced by the concentration levels of the independent variables. An increase in hydrotrope levels corresponded to an increase in %CDR. The positive coefficients in the quadratic equation for %CDR underscored the significant role of these independent variables in augmenting the in-vitro release of Ketoprofen. Similarly, during a comparative dissolution investigation, the optimized KSD9 formulation exhibited remarkable solubility and drug content compared to conventional Ketoprofen dispersible tablets.</p><p><strong>Conclusion: </strong>The synergistic effect of combining two hydrotropic agents significantly increased the solubility of ketoprofen by up to 58 times. The results indicated that the independent variables exerted a positive influence on solubility and %CDR. Furthermore, the responses were contingent on the specific hydrotropes selected, which functioned as the independent variables. Analyzing the r² and ANOVA results suggested that the dependent variables aligned well with the chosen model. Visual representations, such as the 3D response surface plot and contour plot, demonstrated the impact of each hydrotrope individually and when combined. Overall, employing hydrotropes led to improved solubility and %CDR, highlighting a direct proportionality between the rise in solubility and %CDR. Mixed hydrotropic lessens the toxicity associated with individual hydrotrope concentrations while also offering a sustainable and eco-friendly alternative. This study pave
背景:在制药科学中,治疗分子的溶解度曲线对于确定和配制药物以及根据口服生物利用度、代谢转化、生物分布动力学和潜在的毒理学影响等因素评估药物质量至关重要。本研究旨在提高酮洛芬(BCS-II 类)的溶解度参数,因为酮洛芬具有低溶解度和高渗透性:方法:本方法采用芳香族苯甲酸钠和电解质醋酸钠的水托混合物来提高酮洛芬的溶解度参数。采用溶剂蒸发法制备了多批酮洛芬固体分散体,并采用响应面法 3² 因式设计找到了最佳配方。对优化后的配方 KSD9 进行了体外药物溶解、DSC、pXRD 和 SEM 研究:结果:优化后的批次大大提高了酮洛芬的溶解度,这归功于混合水化作用。结果表明,使用水托剂后,溶解度和CDR%都有所提高,这表明溶解度和CDR%的提高成正比。制剂 KSD1-KSD9 的溶解度提高了 2.23 至 5.77 倍,CDR%也从 72.28% 提高到 94.76%。这意味着 CDR 百分比受水力介质的调节,特别是受自变量浓度水平的影响。水力介质浓度的增加对应于 CDR 百分比的增加。CDR%二次方程中的正系数强调了这些自变量在增加酮洛芬体外释放中的重要作用。同样,在溶出度比较研究中,与传统的酮洛芬分散片相比,优化后的 KSD9 制剂在溶出度和药物含量方面都有显著提高:結論:結合兩種促水劑的協同效應可顯著提高酮洛芬的溶解度達 58 倍。结果表明,自变量对溶解度和 CDR%产生了积极影响。此外,反应还取决于作为自变量的特定水处理剂的选择。分析 r² 和方差分析结果表明,因变量与所选模型非常吻合。三维响应面图和等值线图等可视化图示显示了每种水力措施单独使用和组合使用时的影响。总体而言,使用水力喷射剂提高了溶解度和 CDR%,突出了溶解度和 CDR%之间的正比关系。混合水托品降低了与单独水托品浓度相关的毒性,同时也提供了一种可持续的环保替代品。这项研究为今后旨在提高低溶解度药物溶解度的研究铺平了道路,从而扩大了这些药物的临床应用。
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引用次数: 0
Apigenin's Influence on Inflammatory and Epigenetic Responses in Rat Lungs After Radiotherapy. 芹菜素对放疗后大鼠肺部炎症和表观遗传反应的影响
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-23 DOI: 10.2174/0118744710336823241011095632
Fatemeh Rajabinasab, Pooya Hajimirzaei, Fatemeh Ramezani, Fariborz Moayer, Fazel Gorjipour, Alireza Nikoofar, Leila Hasanzadeh, Michael R Hamblin, Atousa Janzadeh, Reza Paydar

Introduction: The lung is a moderately radio-sensitive organ. When cells are damaged due to accidental radiation exposure or treatment, they release molecules that lead to the recruitment of immune cells, accumulating inflammatory cytokines at the site of damage. Apigenin (Api) is a natural flavonoid known for its anti-inflammatory properties. In this study, we investigated the radioprotective properties of Api in the lung.

Methods: Thirty-six Wistar rats were randomly assigned to nine groups: control, radiation (Rad), CMC+Rad, Api10+Rad, and Api20+Rad. Api was administered with an intraperitoneal injection for 7 days, after which the rats were irradiated with 6 Gy whole-body X-ray. At 6 and 72 hours post-irradiation, the rats were euthanized, and their lung tissue was extracted.

Results: Radiation led to increased alveolar wall thickness and the infiltration of macrophages and lymphocytes. Furthermore, the expression levels of inflammatory factors such as a nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-ĸB), Glycogen synthase kinase-3 beta (GSK-3β), transforming growth factor-beta1 (TGF-β1), and epigenetic factors including DNA methyltransferase 3a (DNMT3a) and Histone deacetylase 2 (HDAC2) were elevated in the lung tissue following radiation. Meanwhile, the expression level of IκB-α decreased. However, administration of Api (at both 10&20 mg/kg) reversed the adverse effects of radiation.

Conclusion: Api administration mitigated radiation-induced lung damage by reversing inflammatory and epigenetic changes.

简介肺是一个中度辐射敏感器官。当细胞因意外的辐射照射或治疗而受损时,它们会释放出导致免疫细胞募集的分子,并在受损部位积聚炎症细胞因子。芹菜素(Api)是一种天然类黄酮,以其抗炎特性而闻名。在这项研究中,我们调查了 Api 在肺部的放射保护特性:方法:将 36 只 Wistar 大鼠随机分为 9 组:对照组、辐射(Rad)组、CMC+Rad 组、Api10+Rad 组和 Api20+Rad 组。大鼠腹腔注射 Api 7 天,然后接受 6 Gy 全身 X 射线照射。在照射后 6 小时和 72 小时,对大鼠实施安乐死,并提取其肺部组织:结果:辐射导致肺泡壁厚度增加,巨噬细胞和淋巴细胞浸润。此外,辐射后肺组织中的炎症因子,如 B 细胞卡巴轻多肽基因增强子核因子(NF-ĸB)、糖原合成酶激酶-3 beta(GSK-3β)、转化生长因子-β1(TGF-β1)以及表观遗传因子(包括 DNA 甲基转移酶 3a(DNMT3a)和组蛋白去乙酰化酶 2(HDAC2))的表达水平均升高。同时,IκB-α的表达水平下降。然而,服用 Api(10 毫克/千克和 20 毫克/千克)可逆转辐射的不良影响:结论:通过逆转炎症和表观遗传学变化,服用 Api 可减轻辐射引起的肺损伤。
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引用次数: 0
An Analysis of the Radiosensitiser Applications in the Biomedical Field. 分析放射增敏剂在生物医学领域的应用。
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-02 DOI: 10.2174/0118744710269842240825160247
Teng Sheng Lim, Irman Abdul Rahman, Aminah Umar, Norsyahidah Mohd Hidzir, Kenton Paul Arkill, Razinah Sharif, Mohd Anuar Jonet, Hur Munawar Kabir Mohd, Faizal Mohamed

Background: Various types of radiosensitisers have been introduced from the past until the present day for applications in the biomedical field. However, there is a lack of understanding and comparison between the various parameters introduced in addition to a lack of consensus among researchers on the optimal radiosensitiser for applications in the biomedical field.

Objective: This review aimed to investigate the usage of radiosensitisers in the biomedical field, determine their important parameters, and suggest radiosensitisers with potential among the analysed radiosensitisers.

Results and conclusion: This review has discussed several parameters for radiosensitisers, including median lethal dose, cell survival, tumour size, cell viability, Dose Enhancement Factor (DEF), Reactive Oxygen Species (ROS) concentration, radiosensitiser production complexity, radiosensitiser administration technique, and radiosensitiser toxicity. General trends regarding the development of radiosensitisers, including the types, effectiveness, and their production complexity, have also been discussed within this review article.

背景:从古至今,在生物医学领域应用的放射增感剂种类繁多。然而,除了研究人员对生物医学领域应用的最佳放射增敏剂缺乏共识外,对所引入的各种参数也缺乏了解和比较:本综述旨在调查放射增敏剂在生物医学领域的使用情况,确定其重要参数,并在分析的放射增敏剂中推荐具有潜力的放射增敏剂:本综述讨论了放射增敏剂的几个参数,包括中位致死剂量、细胞存活率、肿瘤大小、细胞活力、剂量增强因子(DEF)、活性氧(ROS)浓度、放射增敏剂生产复杂性、放射增敏剂给药技术和放射增敏剂毒性。本综述文章还讨论了放射增敏剂发展的总体趋势,包括类型、有效性及其生产复杂性。
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引用次数: 0
Left Ventricular Wall Motion as an Additional Valuable Parameter in Diabetic Patients with Normal Myocardial Perfusion Imaging. 左心室壁运动是心肌灌注成像正常的糖尿病患者的另一个重要参数
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-27 DOI: 10.2174/0118744710312688240814100448
Amirhesam Davari, Fatemeh Jalali-Zefrei, Bahareh Gholami-Chabok, Shiva Tabaghi, Soghra Farzipour, Kourosh Delpasand, Seyed Mehdi Mousavi

Background: Gated SPECT is an established technique for assessment of left ventricular function in cardiovascular disease patients. However, there is little information about the influence of diabetes mellitus on gated SPECT parameters. This study was established to assess gated SPECT parameters in Diabetes Mellitus (DM) and non-diabetes mellitus (non-DM) patients with normal Myocardial Perfusion Imaging (MPI).

Methods: In this analytical cross-sectional study, 314 patients (157 DM, 157 non-DM) with normal MPI were enrolled. Prevalence of risk factors for CAD like hypertension (HTN), and dyslipidemia were found to be significantly higher (p <0.01) in DM patients compared to non-DM.

Results: No statistically significant difference was observed among the TID, ESV, EDV, PFR, TTPF, and Wall Thickness (WT) parameters between DM and non-DM patients. Wall motion (Wm) in DM patients was significantly higher compared to non-DM patients. (3.9 ± 0.51 vs. 2.69 ± 0.48 for DM and non-DM patients, respectively, p-value:0.01). Also, there was no significant difference in Wm in the two groups with and without HTN. This shows the independent effect of DM on the Wm.

Conclusion: This study believes that the Wm parameter should be noted for the early diagnosis or prevention of heart disease in DM patients. These findings can indicate the gradual changes in the movements of the left ventricle and the beginning of the progression of diabetic cardiomyopathy.

背景:门控 SPECT 是评估心血管疾病患者左心室功能的一项成熟技术。然而,有关糖尿病对门控 SPECT 参数影响的信息却很少。本研究旨在评估心肌灌注成像(MPI)正常的糖尿病(DM)和非糖尿病(Non-DM)患者的门控 SPECT 参数:在这项横断面分析研究中,共纳入了 314 名心肌灌注成像正常的患者(157 名糖尿病患者,157 名非糖尿病患者)。研究发现,高血压(HTN)和血脂异常等导致 CAD 的危险因素的患病率明显更高(P 结果显示:高血压(HTN)和血脂异常等导致 CAD 的危险因素的患病率明显更高:DM和非DM患者的TID、ESV、EDV、PFR、TTPF和室壁厚度(WT)参数在统计学上无明显差异。DM患者的室壁运动(Wm)明显高于非DM患者。(DM 和非 DM 患者的室壁运动(Wm)分别为 3.9 ± 0.51 vs. 2.69 ± 0.48,P 值:0.01)。此外,有高血压和无高血压的两组患者的 Wm 没有明显差异。结论:本研究认为,在早期诊断或预防 DM 患者的心脏病时应注意 Wm 参数。这些发现可以表明左心室运动的逐渐变化和糖尿病心肌病进展的开始。
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引用次数: 0
Pressed Solid Target Production of 89Zr and its Application for Antibody Labelling. 压制固体靶标生产 89Zr 及其在抗体标记中的应用。
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-22 DOI: 10.2174/0118744710318544240715061530
Anjli Shrivastav, Sonu Maurya, Manish Dixit, Sarita Kumari, Sanjay Gambhir

Objectives: Zirconium-89 ( 89Zr, t1/2=3.27d) is an important + emitting radionuclide used in Positron Emission Tomography (PET) immuno studies due to its unique characteristics and increased demand due to simple and cost-effective production capacity. Production of 89Zr is achieved primarily through solid natural yttrium targets via different target preparation methodologies, such as electrodeposition, pressed foils, and spark plasma sintering. In this study, we have investigated the pressed solid target methodology.

Methods: The Yttrium Oxide (Y2O3) powder was pressed to pellet form and stacked over a different back support plate, such as platinum (Pt), niobium (Nb), and tantalum (Ta). The target was irradiated with approximately 12 MeV proton beam for 10-60 minutes at 20µA current. The irradiated target was purified through a solid phase extraction method via hydroxamate-based resin by manual or automatic approach. The purified 89Zr was analyzed using gamma scintigraphy, and specific activity was calculated through Deferoxamine (DFO) chelation.

Results: 89Zr radionuclide via pressed target was effectively produced with a production yield of 20-30 MBq/µA.h, and the purification was achieved in 35 minutes with (87.46)% average recovery and >98% purity while using automated purification, but manual purification took 2 hours with (91 ± 2)% recovery and >98% purity. The production yield was comparable to the reported pressed target approach. Deferoxamine (DFO) chelation with 89Zr-oxalate was performed with purity >98% and specific activity of 25-30 µCi/mmol.

Conclusion: In this study, we explored the production of 89Zr by pressed targets and purification via manual or automated methods with good radionuclide purity. The chelation with DFO or its analog was performed with good labeling efficiency and stability

.

目的:锆-89(89Zr,t1/2=3.27d)是正电子发射断层扫描(PET)免疫研究中使用的一种重要的+发射放射性核素,因其独特的特性和简单、经济的生产能力而需求增加。89Zr 的生产主要通过不同的靶制备方法,如电沉积、压制箔和火花等离子烧结等,通过固体天然钇靶来实现。在本研究中,我们研究了压制固体靶的方法:方法:将氧化钇(Y2O3)粉末压制成颗粒状,并堆叠在不同的背面支撑板上,如铂(Pt)、铌(Nb)和钽(Ta)。在 20µA 电流下,用大约 12 MeV 的质子束辐照目标 10-60 分钟。辐照后的靶材通过固相萃取法,用羟基氨基甲酸酯树脂进行人工或自动提纯。纯化后的 89Zr 采用伽马闪烁法进行分析,并通过脱氧胺(DFO)螯合计算比活度:结果:通过压制靶有效生产出 89Zr 放射性核素,产量为 20-30 MBq/µA.h,采用自动纯化法时,35 分钟就能完成纯化,平均回收率为 (87.46)%,纯度大于 98%;而手动纯化法需要 2 小时,回收率为 (91 ± 2)%,纯度大于 98%。生产率与报告的压制目标方法相当。用 89Zr-oxalate 进行脱氧胺(DFO)螯合,纯度大于 98%,比活度为 25-30 µCi/mmol:在这项研究中,我们探索了通过压制目标生产 89Zr,并通过手动或自动方法进行纯化,从而获得良好的放射性核素纯度。与 DFO 或其类似物的螯合具有良好的标记效率和稳定性。
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引用次数: 0
Recent Advances in the Diagnosis of Alzheimer's Disease: A Brief Overview of Tau PET Tracers in Nuclear Medicine. 阿尔茨海默病诊断的最新进展:核医学中的 Tau PET 示踪剂简介。
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-19 DOI: 10.2174/0118744710314668240718070109
Farahnaz Aghahosseini, Yalda Salehi, Saeed Farzanefar, Mohsen Bakhshi Kashi, Elisabeth Eppard, Hojjat Ahmadzadehfar, Siroos Mirzaei, Nasim Vahidfar, Ayuob Aghanejad

Dementia (the most common cause of Alzheimer's disease) is defined as a chronic or progressive syndrome with disturbance of multiple cortical functions, the most important of them including memory, learning capacity, comprehension, orientation, calculation, language, and judgement. These cognitive impairments affect the quality of life, behavior, and social relations. Techniques of nuclear medicine provide feasible ways to record the intracellular alterations of disease and deficiencies. In these non-invasive manners, the hippocampal-neocortical disconnection may partly explain the hypo-metabolism incident found in Alzheimer's disease. Based on this fact, the study of all these mechanisms of action is conceivable and achievable by radiopharmaceuticals. This review is aimed at the presentation of radiopharmaceuticals that are developed for the detection of Alzheimer's disease in preclinical and clinical trials.

痴呆症(阿兹海默病最常见的病因)被定义为一种慢性或进行性综合征,患者大脑皮层的多种功能出现紊乱,其中最重要的功能包括记忆力、学习能力、理解力、定向力、计算力、语言和判断力。这些认知障碍会影响生活质量、行为和社会关系。核医学技术为记录疾病和缺陷的细胞内改变提供了可行的方法。在这些非侵入性的方法中,海马-皮质断开可能部分解释了阿尔茨海默病中发现的代谢不足现象。基于这一事实,放射性药物对所有这些作用机制的研究都是可以想象和实现的。本综述旨在介绍在临床前和临床试验中用于检测阿尔茨海默病的放射性药物。
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引用次数: 0
Biological Efficacy of Ionizing Radiation Sources on 3D Organotypic Tissue Slices Assessed by Fluorescence Microscopy. 用荧光显微镜评估电离辐射源对三维有机组织切片的生物效应
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-30 DOI: 10.2174/0118744710293570240419110322
Victoria Shestakova, Anna Smirnova, Anna Yakimova, Sergey Koryakin, Denis Baranovskii, Vyacheslav Saburov, Elena Yatsenko, Alexander Moiseev, Sergey Ivanov, Ekaterina Smirnova, Svetlana Belkina, Grigory Demyashkin, Lyudmila Komarova, Peter Shegay, Andrey Kaprin, Ilya Klabukov

Objective: Traditional cell-based radiobiological methods are inadequate for assessing the toxicity of ionizing radiation exposure in relation to the microstructure of the extracellular matrix. Organotypic tissue slices preserve the spatial organization observed in vivo, making the tissue easily accessible for visualization and staining. This study aims to explore the use of fluorescence microscopy of physiologically compatible 3D tissue cultures to assess the effects of ionizing radiation.

Methods: Organotypic tissue slices were obtained by vibratome, and their mechanical properties were studied. Slices were exposed by two ionizing radiation sources; electron beams (80 Gy and 4 Gy), and soft gamma irradiation (80 Gy and 4 Gy). Two tissue culture protocols were used: the standard (37°C), and hypothermic (30°C) conditions. A qualitative analysis of cell viability in organotypic tissue slices was performed using fluorescent dyes and standard laser confocal microscopy.

Results: Biological dosimetry is represented by differentially stained 200-µm thick organotypic tissue sections related to living and dead cells and cell metabolic activity.

Conclusion: Our results underscore the ability of fluorescence laser scanning confocal microscopy to rapidly assess the radiobiological effects of ionizing radiation in vitro on 3D organotypic tissue slices.

目的:传统的基于细胞的放射生物学方法不足以评估电离辐射照射与细胞外基质微观结构有关的毒性。有机组织切片保留了在体内观察到的空间组织结构,使组织易于观察和染色。本研究旨在探索如何利用荧光显微镜观察生理兼容的三维组织培养物,以评估电离辐射的影响:方法:用振荡器获得有机组织切片,并研究其机械性能。切片受到两种电离辐射源的照射:电子束(80 Gy 和 4 Gy)和软伽马辐照(80 Gy 和 4 Gy)。使用了两种组织培养方案:标准(37°C)和低温(30°C)条件。使用荧光染料和标准激光共聚焦显微镜对有机组织切片中的细胞存活率进行了定性分析:结果:生物剂量测定体现在 200 微米厚的有机组织切片上,活细胞和死细胞以及细胞代谢活动受到不同程度的染色:我们的研究结果表明,荧光激光扫描共聚焦显微镜能够快速评估电离辐射对三维有机组织切片的体外放射生物学效应。
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引用次数: 0
Radiopharmaceuticals Adverse Events Management. 放射性药物不良事件管理。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-29 DOI: 10.2174/0118744710284298240419115911
Ana Agudo Martínez, Gertrudis Sabatel Hernandez, Manuela Molina Mora, Pablo Antonio de la Riva Perez, Rosa Fernandez Lopez, Teresa Cambil Molina, Cinta Calvo Moron

Background and purpose: Radiopharmaceuticals are radioactive compounds used for diagnostic or therapeutic purposes which are most often administered intravenously. Adverse events that may induce both adverse reactions and drug-to-drug interactions with changes in expected biodistribution, potentially affecting patient safety and diagnostic accuracy. Adverse reactions are relatively rare due to the small doses and under-reporting is the norm. The aim of this study is to increase awareness of the need to report in order to create protocols for the management of such adverse events among professionals in a Nuclear Medicine Department.

Methods: A reporting system was established a decade ago through an electronic form to enhance adverse event registration. The radiopharmacist collects data for further communication with National Health authorities and develops an annual report with recommendations on the management of these adverse events.

Results: A total of 128 reports were collected, including 65 cases of extravasations, 18 adverse reactions, and 45 drug interactions. Over the years, reporting has been increasing, adverse reactions occurred at a higher incidence than reported in the literature, and each anomalous biodistribution was analysed for possible drug interaction. The annual reports have been used to develop a local guideline for the management of adverse reactions and recommendations for discontinuation of treatment to avoid interactions with radiopharmaceuticals.

Conclusion: The recognition of adverse events associated with radiopharmaceuticals is increasing, underlining the need for vigilant reporting and improved management strategies. An efficient reporting system promotes awareness of possible interactions between radiopharmaceuticals and other medicines and their potential adverse reactions to enhance patient safety.

背景和目的:放射性药物是用于诊断或治疗目的的放射性化合物,通常通过静脉注射给药。不良反应和药物间相互作用可能会改变预期的生物分布,从而可能影响患者安全和诊断准确性。由于剂量较小,不良反应相对罕见,报告不足是常态。本研究旨在提高核医学科专业人员对报告必要性的认识,以便制定管理此类不良事件的规程:方法:十年前通过电子表格建立了一个报告系统,以加强不良事件登记。放射药剂师收集数据,以便与国家卫生部门进一步沟通,并编写年度报告,就如何处理这些不良事件提出建议:结果:共收集到 128 份报告,其中包括 65 例外渗、18 例不良反应和 45 例药物相互作用。多年来,报告数量不断增加,不良反应的发生率高于文献报告的发生率,对每种异常生物分布都进行了分析,以确定是否存在药物相互作用。年度报告已被用于制定当地的不良反应处理指南和停止治疗的建议,以避免与放射性药物发生相互作用:与放射性药物相关的不良反应越来越多,这说明有必要提高警惕,及时报告并改进管理策略。高效的报告系统可提高人们对放射性药物与其他药物之间可能发生的相互作用及其潜在不良反应的认识,从而加强患者安全。
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引用次数: 0
Guideline Adherence as an Indicator of PET Scan Overuse in an Italian Teaching Hospital: An Observational Study. 意大利一家教学医院将遵守指南作为 PET 扫描过度使用的指标:一项观察性研究。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-22 DOI: 10.2174/0118744710290906240408094829
Giuseppe Lucio Cascini, Marianna Mauro, Barbara Catalfamo, Monica Giancotti, Roberta Muraca

Background: Evidence of inappropriate overuse and underuse of medical procedures has been documented in modern healthcare systems around the world. Excessive use of health services can contribute to a rapid increase in healthcare costs and harm the patient physically and psychologically; conversely, underuse can lead to the inability to provide effective treatments when clinically indicated.

Objective: The study's aim is twofold: a) to measure the appropriateness of PET prescription in a cohort of patients, offering empirical evidence of overuse of health care services; b) to evaluate how the overuse of PET could affect public health expenditure and, consequently, the system's financial sustainability.

Methods: In this observational study, we have analyzed prospectively and retrospectively health patient records who underwent 18F-FDG PET/TC scan at the Nuclear Medicine Department of the University Hospital Mater Domini in Catanzaro (Italy) from 29/09/2022 to 10/02/2023. Patients' diagnostic questions have been defined as appropriate, not completely appropriate and completely inappropriate according to the 18F-FDG PET/CT recommendations defined by the "Conditions of Supply and Indications of Prescriptive Appropriateness of Italian NHS (National Health Systems)" published in the Official Gazette no. 15 of 20 January 2016 (Decree 9 December 2015) and by the AIMN (Italian Association of Nuclear Medicine) guidelines.

Results: We gathered data from 500 oncological patients (242 males and 258 females). The results show that 423/500 of patients' prescriptions were appropriate, while 77/500 of patients' prescriptions were completely inappropriate (63/77) or not completely appropriate (14/77).

Conclusion: Analysis showed a not complete adherence to national guidelines and no shared decision-making approach.

背景:在世界各地的现代医疗保健系统中,都有不适当地过度使用和使用不足医疗程序的证据。过度使用医疗服务会导致医疗成本迅速增加,并对患者的身心造成伤害;反之,使用不足则会导致无法根据临床需要提供有效的治疗:本研究有两个目的:a) 测量一组患者 PET 处方的适当性,提供过度使用医疗服务的实证证据;b) 评估过度使用 PET 如何影响公共卫生支出,进而影响系统的财务可持续性:在这项观察性研究中,我们对 2022 年 9 月 29 日至 2023 年 2 月 10 日期间在卡坦扎罗(意大利)多米尼加母校大学医院核医学科接受 18F-FDG PET/TC 扫描的健康患者记录进行了前瞻性和回顾性分析。根据 2016 年 1 月 20 日第 15 号《官方公报》中公布的 "意大利 NHS(国家卫生系统)的供应条件和处方适宜性指标 "所定义的 18F-FDG PET/TC 建议,患者的诊断问题被定义为适宜、不完全适宜和完全不适宜。结果:我们收集了 500 名肿瘤患者(男性 242 人,女性 258 人)的数据。结果显示,423/500 例患者的处方是合适的,而 77/500 例患者的处方完全不合适(63/77)或不完全合适(14/77):结论:分析表明,国家指导方针没有得到完全遵守,也没有采取共同决策的方法。
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引用次数: 0
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Current radiopharmaceuticals
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