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The Central Composite Design and Artificial Neural Network Coupled with Genetic Algorithm in Optimization and Modeling of the Radiolabeling Process of 177Lu-hydroxyapatite as a Potential Radiosynovectomy Agent. 中心复合设计与人工神经网络结合遗传算法对177lu -羟基磷灰石作为潜在放射滑膜切除药物的放射标记过程进行优化建模。
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.2174/0118744710336283250227020659
Sima Attar Nosrati, Maryam Salahinejad, Mohammad Reza Aboudzadeh, Mojtaba Amiri, Ali Roozbahani

Introduction: A promising material used in radiation synovectomy of small joints is hydroxyapatite, labeled with 177Lu. During the design and production of radiopharmaceuticals, the condition of the radiolabeling process directly influences the radiochemical yield and consequently the quality of the final product so this process necessitates precise optimization.

Methods: In this investigation, a central composite design based on response surface methodology and artificial neural networks modeling coupled with genetic algorithm technique is applied to build predictive models and explore key parameters' effect in hydroxyapatite's radiolabeling process with 177Lu radionuclide. The variables that directly affected the labeling reaction were the initial 177Lu radioactivity, pH, radiolabeling reaction time, and temperature.

Results: Based on the validation data set, the statistical values demonstrate that the artificial neural networks model performs better than the response surface methodology model. The artificial neural networks model has a small mean squared error (9.08 artificial neural networks < 12.36 response surface methodology) and a high coefficient of determination (R2: 0.99 artificial neural networks > 0.93 response surface methodology). The optimum conditions to achieve maximum radiochemical yield based on response surface methodology using artificial neural networks modeling coupled with genetic algorithm were at the initial radioactivity of 177Lu radionuclide = 0.082 Gigabecquerel (GBq), pH = 6.75, time= 22 (min), and temperature = 37.8 (oC).

Conclusion: The ability to generate more data with fewer experiments for optimization and improved production is a pertinent advantage of multivariate optimization methods over traditional methods in radiation-related activities. The central composite design and artificial neural network- genetic algorithm optimization approaches are successfully utilized to create prediction models and investigate the impact of critical variables in the radiolabeling of hydroxyapatite with 177Lu radionuclide.

背景:羟基磷灰石是一种很有前途的材料,用于小关节的放射滑膜切除术,标记为177Lu。在放射性药物的设计和生产过程中,放射性标记过程的条件直接影响到放射化学产率,从而影响到最终产品的质量,因此这一过程需要精确的优化。方法:采用响应面法和人工神经网络建模结合遗传算法的中心复合设计,建立预测模型,探讨关键参数对177Lu放射性核素羟基磷灰石放射性标记过程的影响。直接影响标记反应的变量是初始177Lu放射性、pH、放射性标记反应时间和温度。结果:基于验证数据集,统计值表明人工神经网络模型优于响应面方法模型。人工神经网络模型均方误差小(9.08人工神经网络< 12.36响应面方法),决定系数高(R2: 0.99人工神经网络bb0 0.93响应面方法)。基于人工神经网络建模与遗传算法相结合的响应面法,得到177Lu核素初始放射性= 0.082 GBq, pH = 6.75,时间= 22 (min),温度= 37.8 (oC)时获得最大放化学产率的最佳条件。在与辐射相关的活动中,多元优化方法比传统方法具有更大的优势,即能够以更少的实验产生更多的数据,从而进行优化和提高产量。利用中心复合设计和人工神经网络-遗传算法优化方法建立了预测模型,并研究了177Lu放射性核素对羟基磷灰石放射性标记的影响。
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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 : 2025-01-01 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
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 : 2025-01-01 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 st
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
The Estimation Value of 99mTc-MAA in Comparison with 90Y-PET/MR-based Dosimetry in Selective Internal Radiation Therapy (SIRT) for Liver Malignancies. 99mTc-MAA与90Y-PET/ mr剂量法在肝脏恶性肿瘤选择性内放射治疗(SIRT)中的价值比较
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.2174/0118744710333819250112153859
Nami Yeyin, Mohammad Abuqbeitah, Aysel Namazova, Mustafa Demir

Aim: This study intended to compare the radiation dose estimates to target and nontarget liver compartments from 99mTc-MAA SPECT/CT and 90Y-PET/MR scans in liver tumors treated by 90Y-glass microspheres.

Materials and methods: Dose estimation was performed for twenty-three eligible patients (13M, 10F) after 99mTc-MAA simulation using SPECT/CT imaging, and over 90Y-PET/MR images after 90Y-microsphere therapy. Simplicit90Y™ software was used for voxel-based dosimetry over the liver parenchyma. Dose estimates were obtained for whole healthy liver (HL), healthy injected liver (HIL), and tumor volumes. Pearson correlation, Bland-Altman plot, and Wilcoxon signed-ranks test were used for statistical analysis.

Results: The mean tumor dose was 270 ± 111 Gy, the whole liver parenchyma dose was 26 ± 12 Gy, and the healthy injected liver dose was 55 ± 18 Gy from 99mTc-MAA simulation. 90Y-PET/MR dosimetry yielded a mean tumor dose of 271 ± 125 Gy, a HIL mean dose of 54±18 Gy, and a liver parenchyma dose of 25 ± 12 Gy. An excellent agreement was demonstrated between tumor doses (R2=0.90) and liver doses (R2=0.87), while the agreement was less for HIL doses (R2=0.80). Wilcoxon signed-ranks test yielded no significant difference between the dose estimates for all liver compartments.

Conclusion: It was deduced that 99mTc-MAA SPECT/CT simulation provides valuable dose prediction in 90Y-glass microsphere therapy. Despite the difference in volume measurements and dose estimates with 90Y-PET/MR, the predictive value of the 99mTc-MAA simulation was not affected.

目的:本研究旨在比较90y玻璃微球治疗肝脏肿瘤时,99mTc-MAA SPECT/CT和90Y-PET/MR扫描对靶区和非靶区辐射剂量的估计。材料和方法:对23例符合条件的患者(13M, 10F)进行SPECT/CT 99mTc-MAA模拟后的剂量估计,并对90y微球治疗后超过90y的pet /MR图像进行剂量估计。使用Simplicit90Y™软件对肝实质进行基于体素的剂量测定。获得了整个健康肝脏(HL)、健康注射肝脏(HIL)和肿瘤体积的剂量估计。采用Pearson相关、Bland-Altman图和Wilcoxon符号秩检验进行统计分析。结果:99mTc-MAA模拟的肿瘤平均剂量为270±111 Gy,全肝实质剂量为26±12 Gy,健康肝脏注射剂量为55±18 Gy。90YPET/ MR剂量测定显示肿瘤平均剂量为271±125 Gy, HIL平均剂量为54±18 Gy,肝实质剂量为25±12 Gy。肿瘤剂量(R2=0.90)和肝脏剂量(R2=0.87)之间的一致性很好,而HIL剂量的一致性较低(R2=0.80)。Wilcoxon符号秩检验显示所有肝室的剂量估计值之间没有显著差异。结论:99mTc-MAA SPECT/CT模拟在90y玻璃微球治疗中提供了有价值的剂量预测。尽管90Y-PET/MR在体积测量和剂量估计方面存在差异,但99mTc-MAA模拟的预测值并未受到影响。
{"title":"The Estimation Value of <sup>99m</sup>Tc-MAA in Comparison with <sup>90</sup>Y-PET/MR-based Dosimetry in Selective Internal Radiation Therapy (SIRT) for Liver Malignancies.","authors":"Nami Yeyin, Mohammad Abuqbeitah, Aysel Namazova, Mustafa Demir","doi":"10.2174/0118744710333819250112153859","DOIUrl":"10.2174/0118744710333819250112153859","url":null,"abstract":"<p><strong>Aim: </strong>This study intended to compare the radiation dose estimates to target and nontarget liver compartments from <sup>99m</sup>Tc-MAA SPECT/CT and <sup>90</sup>Y-PET/MR scans in liver tumors treated by <sup>90</sup>Y-glass microspheres.</p><p><strong>Materials and methods: </strong>Dose estimation was performed for twenty-three eligible patients (13M, 10F) after <sup>99m</sup>Tc-MAA simulation using SPECT/CT imaging, and over <sup>90</sup>Y-PET/MR images after <sup>90</sup>Y-microsphere therapy. Simplicit<sup>90</sup>Y™ software was used for voxel-based dosimetry over the liver parenchyma. Dose estimates were obtained for whole healthy liver (HL), healthy injected liver (HIL), and tumor volumes. Pearson correlation, Bland-Altman plot, and Wilcoxon signed-ranks test were used for statistical analysis.</p><p><strong>Results: </strong>The mean tumor dose was 270 ± 111 Gy, the whole liver parenchyma dose was 26 ± 12 Gy, and the healthy injected liver dose was 55 ± 18 Gy from <sup>99m</sup>Tc-MAA simulation. <sup>90</sup>Y-PET/MR dosimetry yielded a mean tumor dose of 271 ± 125 Gy, a HIL mean dose of 54±18 Gy, and a liver parenchyma dose of 25 ± 12 Gy. An excellent agreement was demonstrated between tumor doses (R2=0.90) and liver doses (R2=0.87), while the agreement was less for HIL doses (R2=0.80). Wilcoxon signed-ranks test yielded no significant difference between the dose estimates for all liver compartments.</p><p><strong>Conclusion: </strong>It was deduced that <sup>99m</sup>Tc-MAA SPECT/CT simulation provides valuable dose prediction in <sup>90</sup>Y-glass microsphere therapy. Despite the difference in volume measurements and dose estimates with <sup>90</sup>Y-PET/MR, the predictive value of the <sup>99m</sup>Tc-MAA simulation was not affected.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":"174-181"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitigation of Radiation-induced Acute Hematopoietic System and Intestine Injury by Resveratrol-loaded Polymeric Nanoparticles after Whole Body Irradiation in Mice. 白藜芦醇负载聚合纳米颗粒减轻全身照射后小鼠急性造血系统和肠道损伤
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.2174/0118744710335266250206060602
Mohammad Mohammadi, Amir Kiani, Faranak Aghaz, Elham Arkan, Khodabakhsh Rashidi, Masoud Najafi

Introduction: Radiation-induced damage to the hematopoietic and gastrointestinal systems, especially the intestine, is a major concern for individuals exposed to whole-body radiation during an accident. Resveratrol has shown potential in mitigating radiation-induced toxicity, but its efficacy may be limited by its low bioavailability. In this study, we aimed to evaluate the effectiveness of resveratrol-loaded polymeric-based nanocapsules in mitigating radiation-induced injury in the hematopoietic system and intestine after whole-body exposure to radiation.

Methods: Sixty male mice were randomly divided into four groups: control, radiation (single dose of 7.2 Gy of X-ray) only, resveratrol-loaded polymeric-based nanocapsules (RES-ACN) only, and radiation plus RES-ACN. Mice were exposed to a single dose of 7.2 Gy of X-ray radiation. RES-ACN was administered to the mice starting 24 h after irradiation up to day 7 post-irradiation. Then, blood and tissue samples were collected for complete blood count and histopathological and biochemical evaluation. Survival analyses were also conducted.

Results: The findings showed that RES-ACN significantly mitigated radiation-induced injury to the hematopoietic system and intestine. The histopathological evaluation showed the mitigation of villi shortening, inflammation, and mucous layer thickness following treatment with RES-ACN. Biochemical evaluation also demonstrated a significant increase in the activity of glutathione peroxidase and superoxide dismutase and a significant reduction in the concentrations of malondialdehyde and nitric oxide. Treatment with RES-ACN also showed a significant improvement in some of the blood parameters and increased survival compared to radiation only.

Conclusion: The findings suggest that resveratrol-loaded polymeric-based nanocapsules can be an effective approach to mitigate radiation-induced damage to the hematopoietic system and intestine after whole-body exposure to X-ray radiation in mice. Further research is needed to explore the optimal dose and timing of resveratrol administration and to investigate the potential for clinical translation of this approach.

背景:辐射引起的造血和胃肠道系统损伤,特别是肠道损伤,是事故中暴露于全身辐射的个体的主要问题。白藜芦醇已显示出减轻辐射毒性的潜力,但其生物利用度低可能限制了其功效。在这项研究中,我们旨在评估白藜芦醇负载聚合物纳米胶囊在全身暴露于辐射后减轻造血系统和肠道辐射损伤的有效性。方法:雄性小鼠60只,随机分为对照组、单次给药7.2 Gy x射线组、单次给药白藜芦醇聚合物基纳米胶囊(RES-ACN)组和辐射加RES-ACN组。小鼠接受单剂量7.2 Gy的x射线辐射。从照射后24小时开始至照射后第7天给予小鼠RES-ACN。然后采集血液和组织标本进行全血细胞计数、组织病理学和生化评价。还进行了生存分析。结果:RES-ACN能显著减轻辐射对造血系统和肠道的损伤。组织病理学评估显示,RES-ACN治疗后绒毛缩短,炎症和粘膜层厚度减轻。生化评价也显示谷胱甘肽过氧化物酶和超氧化物歧化酶活性显著增加,丙二醛和一氧化氮浓度显著降低。与单纯放疗相比,RES-ACN治疗也显示出某些血液参数的显著改善和生存率的提高。结论:白藜芦醇负载聚合物纳米胶囊可有效减轻全身x射线照射后小鼠造血系统和肠道的损伤。需要进一步的研究来探索白藜芦醇给药的最佳剂量和时间,并调查该方法的临床转化潜力。
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引用次数: 0
A New Approach to Synthesize Carbon-11-PBR28 and its Clinical Validation in ALS Patients. 合成碳-11- pbr28的新方法及其在ALS患者中的临床验证
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.2174/0118744710341203250220042349
Pardeep Kumar, Aishwarya Kumar, Muddasu Keerthipriya, Chandrika H, Atchayaram Nalini, Seena Vengalil, Kirti Sitani, Chandana Nagaraj, Saikat Dey, Monojit Debnath, Vijayalakshmi K, Talakad N Sathyaprabha

Introduction: Many studies have reported translocator protein (TSPO) overexpression in various neurological disorders. Carbon-11[11C]PBR28 is a widely used TSPO Positron Emission Tomography (PET) radiopharmaceutical. We compared HPLC-based purification with cartridge-based purification and performed PET-MR imaging in ALS patients.

Methods: [11C]PBR28 was synthesized using both an HPLC-based and cartridge-based purification technique on the FX2C chemistry module. We injected 350 ± 20 MBq of the [11C]PBR28 intravenously into the patients diagnosed with amyotrophic lateral syndrome (ALS) limb onset (n =3) and bulbar (n =3). Simultaneous PET-MR dynamic imaging was then performed.

Results: The radiochemical purity exceeded 95% with both methods. Using the HPLC-based method, the radiochemical yield was 11.8 ± 3.3%, molar activity was 253 ± 20.9 GBq/μmol, and the total synthesis time of 25 ± 2 minutes. In contrast, the cartridge-based method yielded a radiochemical yield of 53.0 ± 3.6%, a molar activity of 885 ± 17.7 GBq/μmol, and a total synthesis time of 12 ± 2 minutes. In imaging results, higher activity was observed in the precentral gyrus and cerebellum at 2.5 ± 0.5 minutes in bulbar-onset ALS cases, with a standardized uptake value (SUV) of 2.3 ± 0.3. In contrast, limb-onset ALS cases showed the highest uptake at 0.5 ± 0.2 minutes, with an SUV of 1.5 ± 0.2.

Discussion: The difference in SUV in bulbar and limb onset may be due to pathological changes.

Conclusion: The cartridge-based purification method provided higher radiochemical yield and molar activity as compared to the HPLC purification method.

背景:许多研究报道了转运蛋白(TSPO)在许多神经系统疾病中的过表达。碳-11[11C]PBR28是一种广泛使用的TSPO正电子发射断层扫描(PET)放射性药物。我们比较了基于hplc的纯化和基于墨盒的纯化,并对ALS患者进行了PET-MR成像。方法:在FX2C化学模块中,采用HPLC-based和墨盒-based纯化技术合成[11C]PBR28。进行了所有必要的质量控制并进行了比较。我们将350±20 MBq的[11C]PBR28静脉注射到诊断为肌萎缩侧索综合征(ALS)的人类患者(n = 6)中,并同时进行PETMR动态成像。结果:两种方法的放射化学纯度均大于95%。该方法放射化学收率为11.8±3.3%,摩尔活性为253±20.9 GBq/μmol,总合成时间为25±2 min。该方法的放射化学产率为53.0±3.6%,摩尔活性为885±17.7 GBq/μmol,总合成时间为12±2 min。我们比较了ALS肢体起病(n =3)与ALS球、肢体起病(n =3)的PET-MR成像,时间活动曲线存在差异。在2.5±0.5 min时,球型患者的中央前回和小脑的活动较高,SUV为2.3±0.3,而ALS患者的肢体活动在0.5±0.2 min时最高,SUV为1.5±0.2。结论:该方法具有较高的放射化学产率和摩尔活性。
{"title":"A New Approach to Synthesize Carbon-11-PBR28 and its Clinical Validation in ALS Patients.","authors":"Pardeep Kumar, Aishwarya Kumar, Muddasu Keerthipriya, Chandrika H, Atchayaram Nalini, Seena Vengalil, Kirti Sitani, Chandana Nagaraj, Saikat Dey, Monojit Debnath, Vijayalakshmi K, Talakad N Sathyaprabha","doi":"10.2174/0118744710341203250220042349","DOIUrl":"10.2174/0118744710341203250220042349","url":null,"abstract":"<p><strong>Introduction: </strong>Many studies have reported translocator protein (TSPO) overexpression in various neurological disorders. Carbon-11[<sup>11</sup>C]PBR28 is a widely used TSPO Positron Emission Tomography (PET) radiopharmaceutical. We compared HPLC-based purification with cartridge-based purification and performed PET-MR imaging in ALS patients.</p><p><strong>Methods: </strong>[<sup>11</sup>C]PBR28 was synthesized using both an HPLC-based and cartridge-based purification technique on the FX2C chemistry module. We injected 350 ± 20 MBq of the [<sup>11</sup>C]PBR28 intravenously into the patients diagnosed with amyotrophic lateral syndrome (ALS) limb onset (n =3) and bulbar (n =3). Simultaneous PET-MR dynamic imaging was then performed.</p><p><strong>Results: </strong>The radiochemical purity exceeded 95% with both methods. Using the HPLC-based method, the radiochemical yield was 11.8 ± 3.3%, molar activity was 253 ± 20.9 GBq/μmol, and the total synthesis time of 25 ± 2 minutes. In contrast, the cartridge-based method yielded a radiochemical yield of 53.0 ± 3.6%, a molar activity of 885 ± 17.7 GBq/μmol, and a total synthesis time of 12 ± 2 minutes. In imaging results, higher activity was observed in the precentral gyrus and cerebellum at 2.5 ± 0.5 minutes in bulbar-onset ALS cases, with a standardized uptake value (SUV) of 2.3 ± 0.3. In contrast, limb-onset ALS cases showed the highest uptake at 0.5 ± 0.2 minutes, with an SUV of 1.5 ± 0.2.</p><p><strong>Discussion: </strong>The difference in SUV in bulbar and limb onset may be due to pathological changes.</p><p><strong>Conclusion: </strong>The cartridge-based purification method provided higher radiochemical yield and molar activity as compared to the HPLC purification method.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":"216-223"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prediction of Recurrence using a Stacked Denoising Autoencoder and Multifaceted Feature Analysis of Pretreatment MRI in Patients with Nasopharyngeal Carcinoma. 应用叠置去噪自编码器预测鼻咽癌患者复发及预处理MRI多面特征分析。
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.2174/0118744710384129250327060846
Yibin Liu, Xianwen Wang, Jiongyi Li, Junxiao Gao, Bin He, Xianlong Wang, Lianfang Tian, Bin Li, Qianhui Qiu

Introduction: Nasopharyngeal Carcinoma (NPC) exhibits high incidence in southern China. Despite improved survival with intensity-modulated radiotherapy (IMRT), 10%-20% of patients experience local recurrence. Traditional TNM staging fails to reflect tumor heterogeneity, necessitating robust recurrence prediction models. This study aimed to develop an MRIbased NPC recurrence prediction model by integrating radiomics, deep learning, and clinical features.

Methods: A total of 184 pathologically confirmed NPC patients receiving radical radiotherapy were included. After propensity score matching (1:1), 136 cases were analyzed. Stacked denoising autoencoder (SDAE) extracted deep features from contrast-enhanced T1-weighted MRI. Radiomic features (morphology, texture, first-order statistics), clinical parameters (gender, age, TNM stage), and SDAE features were combined to construct 12 models using SVM, MLP, logistic regression (LR), and random forest (RF). Performance was evaluated via AUC, accuracy, sensitivity, and specificity, with external validation (91 cases).

Results: Model 1 (radiomics + SDAE + clinical features + SVM) achieved the highest AUC (0.89, 95% CI: 0.84-0.93), accuracy (81.5%), sensitivity (67.3%), and specificity (97.9%). External validation showed AUC 0.83, sensitivity 88.9%, and specificity 78%. The DeLong test confirmed no significant AUC difference between internal and external cohorts (P >0.05).

Discussion: The fusion of SDAE-enhanced features outperformed traditional radiomics. SVM demonstrated optimal performance in small samples, likely due to its high-dimensional feature handling and anti-overfitting capability. Limitations include single-center retrospective design and lack of functional imaging (DWI/PET) or molecular markers (EBV-DNA). Future multicenter prospective studies and multimodal data integration are warranted to enhance biological interpretability and clinical utility.

Conclusion: This model provides a tool for early recurrence risk stratification and personalized therapy optimization, advancing precision medicine in NPC management.

背景:预测鼻咽癌复发的策略有待进一步发展和验证。我们基于鼻咽癌(NPC)患者治疗前常规磁共振序列(CE-T1W)的多组学特征融合建立了复发预测模型,用于预测治疗后复发。方法:采用深度无监督堆叠去噪自编码器(stacked denoising autoencoder, SDAE)和多组学特征融合方法建立鼻咽癌复发预测模型。本文收集184例经病理证实并接受根治性综合治疗的新诊断鼻咽癌(NPC)患者的资料和磁共振图像。采用倾向评分匹配(复发:无复发= 1:1)来平衡可能影响复发的临床因素,匹配病例136例。利用SDAE提取深度特征,结合放射组学(radiomics)特征与临床特征的融合特征,采用支持向量机(SVM)、多层感知器(MLP)、逻辑回归(LR)和随机森林(RF)机器学习方法构建模型。比较各模型的平均曲线下面积(AUC)、准确性、敏感性和特异性,评价其预测复发的效果。结果:经过参数调整,建立了12个基于不同融合特征的机器学习模型。模型1 (Radiomics+AutoEncoder+Clinical+SVM)的预测效果更好,平均AUC、准确率、灵敏度和特异性分别为0.89 (95% CI: 0.84- 0.93)、81.5%、67.3%和97.9%。模型2 (Radiomics + AutoEncoder +支持向量机),3 (Radiomics + SVM)模型,模型4 (Radiomics + AutoEncoder +临床+ MLP),模型5 (Radiomics +汽车编码器+ MLP), 6 (Radiomics + MLP)模型,模型7 (Radiomics + AutoEncoder +临床+ LR)模型8 (Radiomics + AutoEncoder + LR), 9 (Radiomics + LR)模型,模型10 (Radiomics +汽车编码器+临床+ RF), 11 (Radiomics + AutoEncoder + RF)模型,模型12 (Radiomics + RF)实现了auc的0.87,0.87,0.82,0.80,0.82,0.82,0.78,0.80,0.81,0.80,和0.82,分别。结论:基于鼻咽癌患者治疗前CE-T1WI建立的放射组学+autoEncoder+临床融合特征预测鼻咽癌复发的SVM模型具有较好的预测效果,且较为可靠,可为临床诊疗决策和干预提供更多信息和帮助。
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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 : 2025-01-01 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
Harnessing Radionuclides: Unveiling the Promising Role of Radiopharmaceuticals in Cancer Theranostics and Palliative Care. 利用放射性核素:揭示放射性药物在癌症治疗和姑息治疗中的有希望的作用。
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.2174/0118744710337420250102054532
Mihai Cozmin, Ionut Iulian Lungu, Radu Cernei, George Alexandru Marin, Letitia Doina Duceac, Gabriela Calin, Marius Gabriel Dabija, Cristian Gutu, Elena Roxana Bogdan Goroftei, Alina Stefanache, Tudor Ciuhodaru

Introduction: In the context of modern oncology, radiogenic elements have emerged as pivotal tools for targeted cancer therapies. Elements like Iodine-131 and Yttrium-90 offer unique radiological properties that allow precise treatment delivery. This article explores their growing importance and potential in reshaping the landscape of cancer therapy.

Methods: Utilizing a systematic literature search, relevant studies, clinical trials, and research articles were collected from databases. The selected material was scrutinized to extract insights into the mechanisms, applications, advantages, and challenges of radiogenic elements. These results are combined in the study to give a perceptive picture of how contemporary oncology treatment is developing.

Results: The article reveals a comprehensive analysis of the outcomes derived from the study of radiogenic elements in contemporary cancer treatment. The results highlight the diverse applications of radionuclides like Iodine-131, Yttrium-90, and actinides in targeted therapies. It showcases their ability to selectively damage cancer cells while sparing healthy tissues, emphasizing precision and efficacy. The review underscores the increasing importance of personalized medicine, combination therapies, and the potential of emerging alpha-particle-based treatments. Furthermore, the results shed light on the challenges posed by radiation safety and potential side effects, prompting a need for vigilant management. This comprehensive examination of results provides a nuanced understanding of the pivotal role that radiogenic elements play in shaping the future of modern oncology therapy.

Conclusion: The article examines the role of radiogenic elements in contemporary cancer treatment. It highlights the significance of elements like 131I, 90Y, and actinides in targeted therapies, discussing their mechanisms and applications. The article emphasizes personalized medicine, combination therapies, and emerging alpha-particle-based treatments. Challenges, including radiation safety and side effects, are also addressed. The review anticipates a promising future where radiogenic elements contribute to precise, effective, and patient-centered cancer care.

背景:在现代肿瘤学的背景下,放射基因元件已经成为靶向癌症治疗的关键工具。像碘-131和钇-90这样的元素具有独特的放射特性,可以进行精确的治疗。本文探讨了它们在重塑癌症治疗前景方面日益增长的重要性和潜力。方法:采用系统的文献检索方法,从数据库中收集相关研究、临床试验和研究文章。对选定的材料进行了仔细审查,以深入了解放射性成因元素的机制、应用、优势和挑战。这些结果在研究中结合起来,给出了当代肿瘤治疗发展的直观图景。结果:本文对当代癌症治疗中放射原性元素的研究结果进行了综合分析。这些结果强调了放射性核素如碘-131、钇-90和锕系元素在靶向治疗中的不同应用。它展示了它们在保留健康组织的同时选择性破坏癌细胞的能力,强调了准确性和有效性。这篇综述强调了个性化医疗、联合治疗以及新兴的基于α粒子的治疗的潜力日益增加的重要性。此外,研究结果揭示了辐射安全和潜在副作用带来的挑战,促使人们需要警惕管理。对结果的全面检查提供了对放射基因元素在塑造现代肿瘤治疗未来中所起关键作用的细致入微的理解。结论:本文探讨了放射原性元素在当代肿瘤治疗中的作用。强调了131I、90Y和锕系元素在靶向治疗中的重要性,并讨论了它们的作用机制和应用。文章强调个性化医疗、联合治疗和新兴的基于α粒子的治疗。还讨论了包括辐射安全和副作用在内的挑战。这篇综述预测了一个有希望的未来,放射基因元素有助于精确、有效和以患者为中心的癌症治疗。
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引用次数: 0
Evaluating the Effectiveness of Geant4 Software in Measuring the Damage Caused by Ti48 Ion Radiation on Nerve Cells, in Comparison to the Biophysical Model and Empirical Data. 评价Geant4软件测量Ti48离子辐射对神经细胞损伤的有效性,比较生物物理模型和经验数据。
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-01 DOI: 10.2174/0118744710367266250506050409
Habiballah Moradi, Eman Obeidavi, Akbar Aliasgharzadeh, Bagher Farhood, Mohammad Esmail Shahabodin

Introduction: Presently, heavy particle ion radiation therapy is commonly utilized for the treatment of deep-seated malignancies, such as brain tumors. In addition to tumor treatment, these particles may negatively impact healthy nerve cells. Therefore, it is essential to investigate the radiobiological effects of these radiations on cells. Simulation studies that model the radiation of heavy particles and the exact geometrical configuration of nerve cells are essential and effective in evaluating potential cellular damage.

Methods: The NEURON software was employed in Geant4 code to simulate an individual nerve cell (ID no: NMO 06176) and a network of ten neural cells subjected to bombardment by Ti48 ion particles at an energy of 600 MeV/u.

Results: The absorbed energy differs among several components of individual cells and neural networks, including the soma and dendrites. The absorbed doses from Ti48 radiation in individual nerve cells and dendritic networks surpass those in the cell body, and this ratio remains consistent as the dosage escalates. The decrease in the initial length of dendrites in both individual cells and neuronal networks intensifies with increased dosages. ; Discussion: The simulation results demonstrate that dendrites absorb a higher radiation dose than the soma, resulting in greater structural damage. This finding highlights the vulnerability of neuronal networks to high-LET radiation, with important implications for space radiation protection and clinical radiotherapy planning.

Conclusion: The diminution of dendritic length due to Ti48 radiation is more significant within the cellular network compared to isolated nerve cells.

目前,重粒子离子放射治疗被广泛用于治疗深部恶性肿瘤,如脑肿瘤。除了肿瘤治疗外,这些颗粒还可能对健康的神经细胞产生负面影响。因此,有必要研究这些辐射对细胞的放射生物学效应。模拟重粒子辐射和神经细胞的精确几何结构的模拟研究对于评估潜在的细胞损伤是必要和有效的。材料和方法:在Geant4代码中使用NEURON软件模拟单个神经细胞(ID号:NMO 06176)和十个神经细胞组成的网络受到能量为600 MeV/u的Ti48离子粒子轰击。结果:细胞和神经网络的不同组成部分(包括体细胞和树突)吸收能量不同。Ti48辐射在单个神经细胞和树突状网络中的吸收剂量超过了细胞体中的吸收剂量,并且随着剂量的增加,这一比例保持一致。随着剂量的增加,单个细胞和神经元网络中树突初始长度的减少会加剧。结论:与分离的神经细胞相比,Ti48辐射导致的树突长度减少在细胞网络内更为显著。
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引用次数: 0
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