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Exposure to Low-Frequency Radiation Changes the Expression of Nestin, VEGF, BCRP and Apoptosis Markers During Glioma Treatment Strategy: An In Vitro Study 在胶质瘤治疗策略中,暴露于低频辐射改变Nestin、VEGF、BCRP和凋亡标志物的表达:一项体外研究
4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-10-04 DOI: 10.2174/0118744710258350230921065159
Maryam Amirinejad, Seyed Hassan Eftekhar-Vaghefi, Seyed Noureddin Nematollahi-Mahani, Moein Salari, Rasoul Yahyapour, Meysam Ahmadi-Zeidabadi
Background: Exposure to physical contamination during chemotherapy, including non-ionizing electromagnetic field, raising concerns about the widespread sources of exposure to this type of radiation. Glioblastoma multiform (GBM) is an aggressive tumor of the central nervous system that is hard to treat due to resistance to drugs such as temozolomide (TMZ). Objective: Electromagnetic fields (EMF) and haloperidol (HLP) may have anticancer effects. In this study, we investigated the effects of TMZ, HLP, and EMF on GBM cell lines and analyzed the association between non-ionizing radiation and the risk of change in drug performance. Methods: Cell viability and reactive oxygen species (ROS) generation were measured by MTT and NBT assay, respectively. Then, the expression levels of breast cancer-resistant protein (BCRP), Bax, Bcl2, Nestin, vascular endothelial growth factor (VEGF) genes, and P53, Bax, and Bcl2 Proteins were evaluated by real-time PCR and western blot. Results: Co-treatment of GBM cells by HLP and TMZ enhanced apoptosis in T-98G and A172 cells by increasing the expression of P53 and Bax and decreasing Bcl-2. Interestingly, exposure of GBM cells to EMF decreased apoptosis in the TMZ+HLP group. Conclusion: In conclusion, EMF reduced the synergistic effect of TMZ and HLP. This hypothesis that patients who are treated for brain tumors and suffer from depression should not be exposed to EMF is proposed in the present study. There appears to be an urgent need to reconsider exposure limits for low-frequency magnetic fields, based on experimental and epidemiological research, the relationship between exposure to non-ionizing radiation and adverse human health effects.
背景:化疗期间暴露于物理污染,包括非电离电磁场,引起人们对这类辐射暴露的广泛来源的关注。多形性胶质母细胞瘤(GBM)是一种侵袭中枢神经系统的肿瘤,由于对替莫唑胺(TMZ)等药物具有耐药性而难以治疗。目的:电磁场(EMF)和氟哌啶醇(HLP)可能具有抗癌作用。在这项研究中,我们研究了TMZ、HLP和EMF对GBM细胞系的影响,并分析了非电离辐射与药物性能变化风险之间的关系。方法:采用MTT法和NBT法分别测定细胞活力和活性氧(ROS)生成。然后采用实时荧光定量PCR和western blot检测乳腺癌耐药蛋白(BCRP)、Bax、Bcl2、Nestin、血管内皮生长因子(VEGF)基因以及P53、Bax、Bcl2蛋白的表达水平。结果:HLP和TMZ共同作用GBM细胞后,T-98G和A172细胞凋亡增加,P53、Bax表达增加,Bcl-2表达降低。有趣的是,TMZ+HLP组GBM细胞暴露于EMF减少了凋亡。结论:电磁场降低了TMZ与HLP的协同作用。目前的研究提出了这样一种假设,即接受脑肿瘤治疗并患有抑郁症的患者不应暴露于电磁场。在实验和流行病学研究的基础上,似乎迫切需要重新考虑低频磁场的接触限值,以及接触非电离辐射与人体健康不良影响之间的关系。
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引用次数: 0
A Computed Tomography-based Radiomics Analysis of Low-energy Proximal Femur Fractures in the Elderly Patients. 老年患者低能量股骨近端骨折的ct放射组学分析。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-05 DOI: 10.2174/1874471016666230321120941
Seyed Mohammad Mohammadi, Samir Moniri, Payam Mohammadhoseini, Mohammad Ghasem Hanafi, Maryam Farasat, Mohsen Cheki

Introduction: Low-energy proximal femur fractures in elderly patients result from factors, like osteoporosis and falls. These fractures impose high rates of economic and social costs. In this study, we aimed to build predictive models by applying machine learning (ML) methods on radiomics features to predict low-energy proximal femur fractures.

Methods: Computed tomography scans of 40 patients (mean ± standard deviation of age = 71 ± 6) with low-energy proximal femur fractures (before a fracture occurs) and 40 individuals (mean ± standard deviation of age = 73 ± 7) as a control group were included. The regions of interest, including neck, trochanteric, and intertrochanteric, were drawn manually. The combinations of 25 classification methods and 8 feature selection methods were applied to radiomics features extracted from ROIs. Accuracy and the area under the receiver operator characteristic curve (AUC) were used to assess ML models' performance.

Results: AUC and accuracy values ranged from 0.408 to 1 and 0.697 to 1, respectively. Three classification methods, including multilayer perceptron (MLP), sequential minimal optimization (SMO), and stochastic gradient descent (SGD), in combination with the feature selection method, SVM attribute evaluation (SAE), exhibited the highest performance in the neck (AUC = 0.999, 0.971 and 0.971, respectively; accuracy = 0.988, 0.988, and 0.988, respectively) and the trochanteric (AUC = 1, 1 and 1, respectively; accuracy = 1, 1 and 1, respectively) regions. The same methods demonstrated the highest performance for the combination of the 3 ROIs' features (AUC = 1, 1 and 1, respectively; accuracy =1, 1 and 1, respectively). In the intertrochanteric region, the combination methods, MLP + SAE, SMO + SAE, and SGD + SAE, as well as the combination of the SAE method and logistic regression (LR) classification method exhibited the highest performance (AUC = 1, 1, 1 and 1, respectively; accuracy= 1, 1, 1 and 1, respectively).

Conclusion: Applying machine learning methods to radiomics features is a powerful tool to predict low-energy proximal femur fractures. The results of this study can be verified by conducting more research on bigger datasets.

老年患者股骨近端低能量骨折是由骨质疏松和跌倒等因素引起的。这些骨折造成了很高的经济和社会成本。在这项研究中,我们旨在通过应用放射组学特征的机器学习(ML)方法建立预测模型,以预测低能量股骨近端骨折。方法:选取股骨近端低能性骨折(发生骨折前)患者40例(平均±年龄标准差= 71±6)和对照组40例(平均±年龄标准差= 73±7)进行计算机断层扫描。手动绘制感兴趣的区域,包括颈部、转子和转子间。将25种分类方法和8种特征选择方法组合应用于roi中提取的放射组学特征。准确度和接收算子特征曲线下面积(AUC)用于评估ML模型的性能。结果:AUC值为0.408 ~ 1,准确度为0.697 ~ 1。多层感知器(MLP)、顺序最小优化(SMO)和随机梯度下降(SGD)三种分类方法与特征选择方法、支持向量机属性评价(SAE)相结合,在颈部表现出最高的性能(AUC分别为0.999、0.971和0.971;准确度分别为0.988、0.988、0.988)和转子(AUC分别为1、1、1);精度分别为1、1和1)区域。同样的方法在3个roi特征的组合下表现出最高的性能(AUC分别= 1,1和1);精度分别为1、1和1)。在粗隆间区,MLP + SAE、SMO + SAE和SGD + SAE组合方法以及SAE方法与logistic回归(LR)分类方法的组合方法表现出最高的性能(AUC分别为1、1、1和1;精度分别为1、1、1和1)。结论:将机器学习方法应用于放射组学特征是预测低能量股骨近端骨折的有力工具。这项研究的结果可以通过在更大的数据集上进行更多的研究来验证。
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引用次数: 0
Cardiac Injury Following Chemo/Radiation Therapy: An Updated Review on Mechanisms and Therapeutic Approaches. 化疗/放疗后心脏损伤:机制和治疗方法的最新综述。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-05 DOI: 10.2174/1874471016666230214101830
Krishanveer Singh, Ameer A Alameri, Ammar Ali Hamza, Moaed E Al-Gazally, Sarvar Temurovich Islomov, Rasha Fadhel Obaid, Andrés Alexis Ramírez-Coronel, Munther Abosaooda, Rasoul Yahyapour, Masoud Najafi

Cardiovascular disorders are among the critical side effects of cancer therapy. Damage to the function and normal structure of the heart can cause serious threats to patients that are being treated for cancer. Cardiovascular complications may be induced by various types of chemotherapy drugs and also radiation therapy. The severity of cardiovascular toxicity depends on several factors, such as types of drugs, tumor location for radiotherapy, the presence of cardiac disease history, the dose of drugs or ionizing radiation, etc. Radiotherapy and chemotherapy can cause heart diseases through various mechanisms, such as oxidative stress, inflammation, cell death, fibrosis, endothelial to mesenchymal transition (EndMT), etc. Chronic inflammation following damage to a huge number of cells can trigger more accumulation of inflammatory cells and chronic release of reactive oxygen species (ROS) and nitric oxide (NO). Oxidative stress can induce more cell death and cardiac remodeling through damage to vessels and valvular and disruption of the normal structure of the extracellular matrix. These changes may lead to cardiomyopathy, myocarditis, pericarditis, and vascular disorders that may lead to heart attack and death. This review provides basic information on cellular and molecular mechanisms of different types of cardiovascular disorders following cancer therapy by radiation or chemotherapy. We also recommend some adjuvants and targets to reduce the risk of heart toxicity by radiation/chemotherapy.

心血管疾病是癌症治疗的主要副作用之一。对心脏功能和正常结构的损害会对正在接受癌症治疗的患者造成严重威胁。心血管并发症可由各种化疗药物和放射治疗引起。心血管毒性的严重程度取决于几个因素,如药物的种类、肿瘤放射治疗的位置、是否有心脏病史、药物或电离辐射的剂量等。放疗和化疗可通过多种机制引起心脏病,如氧化应激、炎症、细胞死亡、纤维化、内皮细胞向间充质细胞转化(EndMT)等。大量细胞受损后的慢性炎症会引发更多炎症细胞的积累和活性氧(ROS)和一氧化氮(NO)的慢性释放。氧化应激可通过损伤血管和瓣膜以及破坏细胞外基质的正常结构诱导更多的细胞死亡和心脏重塑。这些变化可能导致心肌病、心肌炎、心包炎和可能导致心脏病发作和死亡的血管疾病。本文综述了不同类型的癌症放疗或化疗后心血管疾病的细胞和分子机制。我们还推荐一些佐剂和靶点来降低放化疗引起的心脏毒性风险。
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引用次数: 5
DTPA(DOTA)-Nimotuzumab Radiolabeling with Generator-produced Thorium for Radioimmunotherapy of EGFR-overexpressing Carcinomas. DTPA(DOTA)-尼莫妥珠单抗用发电机产生的钍进行放射免疫标记,用于表皮生长因子受体表达过高的癌症的放射免疫治疗。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-05 DOI: 10.2174/1874471016666230221102518
Magdiel G Bravo, Bayirta V Egorova, Aleksandr N Vasiliev, Elena V Lapshina, Stanislav V Ermolaev, Mikhail O Durymanov

Introduction: The feasibility of preparing the "in-house" generators and the Th- DTPA(DOTA)-Nimotuzumab radioimmunoconjugate was evaluated. 226Th is perspective for TAT, however, due to short half-life it is preferable to apply this radionuclide for readily available epithelial malignancies. Nimotuzumab being specific for EGFR expressing cells as a targeting moiety is considered to be suitable for thorium delivery.

Methods: TEVA extraction chromatographic resin and anion exchange resin AG 1x8 were used as sorbents for 226Th generator. In order to determine features of labeling by Th4+ we applied 234Th as a longer-lived analog of short-lived 226Th and the immunoconjugates DTPA(DOTA)-Nimotuzumab were used for radiolabeling.

Results: The generator on the base of TEVA resin has shown higher volume activity of the product compared to the AG 1x8. The 226Th volume concentration was up to 80%/mL. The radiolabeling of BFCA by thorium radioisotopes reached 95% at the MR(Th:p-SCN-Bn-DTPA) = 1:100 and 86% for MR(Th:p-SCN-Bn-DOTA) = 1:5000 at 90°C. The procedure of Nimotuzumab labeling with Th4+ for radiotherapy of EGFR-overexpressing carcinomas was established. The overall labeling yield in both radioimmunoconjugates - DTPA and DOTA functionalized - was in the range of 45-50%. The immunoconjugate Nimotuzumab-p-SCN-Bn-DTPA was obtained with a molar ratio 1:25 (Nimotuzumab: BFCA), within 1 hour of conjugation at 25°C and labelled via postconjugation approach. Whereas Nimotuzumab-p-SCN-Bn-DOTA was obtained at the same conditions, but radiolabeled by the method of pre-conjugation.

Conclusion: Thorium-234 incorporation into both radioimmunoconjugates reached 45-50%. It has been shown that Th-DTPA-Nimotuzumab radioimmunoconjugate specifically bound with EGFR overexpressing epidermoid carcinoma A431 cells.

简介对制备 "内部 "发生器和Th- DTPA(DOTA)-尼莫妥珠单抗放射免疫结合剂的可行性进行了评估。226Th 是 TAT 的透视剂,但由于半衰期较短,因此最好将这种放射性核素用于现成的上皮恶性肿瘤。尼妥珠单抗作为靶向分子,对表皮生长因子受体表达细胞具有特异性,因此被认为适用于钍的输送:方法:使用 TEVA 提取色谱树脂和 AG 1x8 阴离子交换树脂作为 226Th 发生器的吸附剂。为了确定 Th4+ 标记的特征,我们使用 234Th 作为短效 226Th 的长效类似物,并使用免疫结合剂 DTPA(DOTA)-Nimotuzumab 进行放射性标记:结果:与 AG 1x8 相比,以 TEVA 树脂为基础的发生器显示出更高的产品体积活性。226Th 体积浓度高达 80%/毫升。在 90°C 下,钍放射性同位素对 BFCA 的放射性标记率在 MR(Th:p-SCN-Bn-DTPA) = 1:100 时达到 95%,在 MR(Th:p-SCN-Bn-DOTA) = 1:5000 时达到 86%。用 Th4+ 标记尼莫妥珠单抗用于表皮生长因子受体过表达癌的放射治疗的程序已经建立。两种放射免疫缀合物(DTPA 和 DOTA 功能化)的总体标记率在 45-50% 之间。尼莫妥珠单抗-p-SCN-Bn-DTPA免疫轭合物的摩尔比为1:25(尼莫妥珠单抗:BFCA),在25°C下轭合后1小时内获得,并通过后轭合法进行标记。而尼莫妥珠单抗-p-SCN-Bn-DOTA是在相同条件下获得的,但采用了预共轭法进行放射性标记:结论:钍-234在两种放射免疫结合剂中的掺入率都达到了45-50%。研究表明,Th-DTPA-Nimotuzumab 放射免疫结合剂能与表皮生长因子受体过度表达的表皮样癌 A431 细胞特异性结合。
{"title":"DTPA(DOTA)-Nimotuzumab Radiolabeling with Generator-produced Thorium for Radioimmunotherapy of EGFR-overexpressing Carcinomas.","authors":"Magdiel G Bravo, Bayirta V Egorova, Aleksandr N Vasiliev, Elena V Lapshina, Stanislav V Ermolaev, Mikhail O Durymanov","doi":"10.2174/1874471016666230221102518","DOIUrl":"10.2174/1874471016666230221102518","url":null,"abstract":"<p><strong>Introduction: </strong>The feasibility of preparing the \"in-house\" generators and the Th- DTPA(DOTA)-Nimotuzumab radioimmunoconjugate was evaluated. <sup>226</sup>Th is perspective for TAT, however, due to short half-life it is preferable to apply this radionuclide for readily available epithelial malignancies. Nimotuzumab being specific for EGFR expressing cells as a targeting moiety is considered to be suitable for thorium delivery.</p><p><strong>Methods: </strong>TEVA extraction chromatographic resin and anion exchange resin AG 1x8 were used as sorbents for <sup>226</sup>Th generator. In order to determine features of labeling by Th4<sup>+</sup> we applied <sup>234</sup>Th as a longer-lived analog of short-lived <sup>226</sup>Th and the immunoconjugates DTPA(DOTA)-Nimotuzumab were used for radiolabeling.</p><p><strong>Results: </strong>The generator on the base of TEVA resin has shown higher volume activity of the product compared to the AG 1x8. The <sup>226</sup>Th volume concentration was up to 80%/mL. The radiolabeling of BFCA by thorium radioisotopes reached 95% at the MR(Th:p-SCN-Bn-DTPA) = 1:100 and 86% for MR(Th:p-SCN-Bn-DOTA) = 1:5000 at 90°C. The procedure of Nimotuzumab labeling with Th4+ for radiotherapy of EGFR-overexpressing carcinomas was established. The overall labeling yield in both radioimmunoconjugates - DTPA and DOTA functionalized - was in the range of 45-50%. The immunoconjugate Nimotuzumab-p-SCN-Bn-DTPA was obtained with a molar ratio 1:25 (Nimotuzumab: BFCA), within 1 hour of conjugation at 25°C and labelled <i>via</i> postconjugation approach. Whereas Nimotuzumab-p-SCN-Bn-DOTA was obtained at the same conditions, but radiolabeled by the method of pre-conjugation.</p><p><strong>Conclusion: </strong>Thorium-234 incorporation into both radioimmunoconjugates reached 45-50%. It has been shown that Th-DTPA-Nimotuzumab radioimmunoconjugate specifically bound with EGFR overexpressing epidermoid carcinoma A431 cells.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":"16 3","pages":"233-242"},"PeriodicalIF":2.3,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9642012","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
Gamma Knife Radiosurgery Modulates micro-RNA Levels in Patients with Brain Metastasis. 伽玛刀放射治疗可调节脑转移患者的微rna水平。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-05 DOI: 10.2174/1874471016666230202164557
Imran Khan, Kerime Akdur, Sadaf Mahfooz, Elif Burce Elbasan, Ayten Sakarcan, Busra Karacam, Georges Sinclair, Sahabettin Selek, Fahri Akbas, Mustafa Aziz Hatiboglu

Background: The relation between micro-RNA (miRNA) modulation and immune cell activity in high-dose radiation settings is not clearly understood.

Objective: To investigate the role of stereotactic radiosurgery (SRS) in (i) the regulation of tumorsuppressor and oncogenic miRNAs as well as (ii) its effect on specific immune cell subsets in patients with metastatic brain tumors (MBT).

Methods: 9 MBT patients who underwent gamma knife-based stereotactic radiosurgery (GKRS) and 8 healthy individuals were included. Serum samples were isolated at three-time intervals (before GKRS, 1 hour, and 1-month post-GKRS). Expressions of tumor-suppressor (miR-124) and oncogenic (miR-21, miR-181a, miR-23a, miR-125b, and miR-17) miRNAs were quantified by qPCR. The lymphocytic frequency (CD3+, CD4+, CD8+, CD56+, CD19+, and CD16+) was investigated by means of flow cytometry.

Results: The median age was 64 years (range: 50-73 years). The median prescription dose was 20Gy (range: 16Gy-24Gy), all delivered in a single fraction. The median overall survival and progression- free survival were 7.8 months (range: 1.7-14.9 months) and 6.7 months (range: 1.1-11.5 months), respectively. Compared to healthy controls, baseline levels of oncogenic miRNAs were significantly higher, while tumor-suppressing miRNA levels remained markedly lower in MBT patients prior to GKRS. Following GKRS, there was a reduction in the expression of miR-21, miR-17, and miR-181a; simultaneously, increased expression increased of miR-124 was observed. No significant difference in immune cell subsets was noted post GKRSIn a similar fashion. We noted no correlation between patient characteristics, radiosurgery data, miRNA expression, and immune cell frequency.

Conclusion: For this specific population with MBT disease, our data suggest that stereotactic radiosurgery may modulate the expression of circulating tumor-suppressor and oncogenic miRNAs, ultimately enhancing key anti-tumoral responses. Further evaluation with larger cohorts is warranted.

背景:在高剂量辐射环境下,微rna (miRNA)调节与免疫细胞活性之间的关系尚不清楚。目的:探讨立体定向放射手术(SRS)在转移性脑肿瘤(MBT)患者中(i)肿瘤抑制因子和致癌mirna的调节以及(ii)特异性免疫细胞亚群的作用。方法:选取9例行伽玛刀立体定向放射治疗(GKRS)的MBT患者和8例健康人。每隔三个时间间隔(GKRS前、1小时和GKRS后1个月)分离血清样本。通过qPCR定量肿瘤抑制mirna (miR-124)和致癌mirna (miR-21、miR-181a、miR-23a、miR-125b和miR-17)的表达。流式细胞术检测淋巴细胞频率(CD3+、CD4+、CD8+、CD56+、CD19+、CD16+)。结果:中位年龄64岁(范围:50-73岁)。处方中位剂量为20Gy(范围:16Gy-24Gy),均为单次给药。中位总生存期和无进展生存期分别为7.8个月(1.7-14.9个月)和6.7个月(1.1-11.5个月)。与健康对照相比,GKRS前MBT患者的致癌miRNA基线水平显著升高,而肿瘤抑制miRNA水平仍显著降低。GKRS后,miR-21、miR-17和miR-181a的表达降低;同时观察到miR-124表达升高。GKRSIn后免疫细胞亚群无显著差异。我们注意到患者特征、放射手术数据、miRNA表达和免疫细胞频率之间没有相关性。结论:对于这一特定的MBT疾病人群,我们的数据表明,立体定向放射手术可能调节循环肿瘤抑制因子和致癌mirna的表达,最终增强关键的抗肿瘤反应。有必要在更大的队列中进行进一步评价。
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引用次数: 0
Promising Radiopharmaceutical Tracers for Detection of Cardiotoxicity in Cardio-oncology. 有前途的放射性药物示踪剂在心脏肿瘤中检测心脏毒性。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-05 DOI: 10.2174/1874471016666230228102231
Zahra Shaghaghi, Fatemeh Jalali Zefrei, Arsalan Salari, Seyed Amineh Hojjati, Seyed Aboozar Fakhr Mousavi, Soghra Farzipour

Cancer treatment has the potential to cause cardiovascular issues and can encourage the appearance of all aspects of cardiac disease, including coronary heart disease, myocardial disease, heart failure, structural heart disease, and rhythm problems. Imaging is required for both diagnostic workup and therapy monitoring for all possible cardiovascular side effects of cancer therapy. Echocardiography is the cardiac imaging gold standard in cardio-oncology. Despite advancements in its use, this method is often not sensitive to early-stage or subclinical impairment. The use of molecular imaging technologies for diagnosing, assessing, and tracking cardiovascular illness as well as for treating, it is fast growing. Molecular imaging techniques using biologically targeted markers are gradually replacing the traditional anatomical or physiological approaches. They offer unique insight into patho-biological processes at the molecular and cellular levels and enable the evaluation and treatment of cardiovascular disease. This review paper will describe molecularbased single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging techniques that are now available and in development to assess post-infarction cardiac remodeling. These methods could be used to evaluate important biological processes such as inflammation, angiogenesis, and scar formation.

癌症治疗有可能引起心血管疾病,并可能促使心脏病的各个方面出现,包括冠心病、心肌疾病、心力衰竭、结构性心脏病和心律问题。对于癌症治疗的所有可能的心血管副作用,诊断检查和治疗监测都需要影像学检查。超声心动图是心脏肿瘤学中心脏成像的金标准。尽管在使用上取得了进步,但这种方法通常对早期或亚临床损害不敏感。分子成像技术在诊断、评估、追踪心血管疾病以及治疗方面的应用正在迅速增长。利用生物靶向标记的分子成像技术正逐渐取代传统的解剖学或生理学方法。它们在分子和细胞水平上对病理生物学过程提供了独特的见解,并使心血管疾病的评估和治疗成为可能。这篇综述文章将描述基于分子的单光子发射计算机断层扫描(SPECT)和正电子发射断层扫描(PET)成像技术,这些技术现在可用和正在开发中,用于评估梗死后心脏重构。这些方法可用于评估重要的生物过程,如炎症、血管生成和疤痕形成。
{"title":"Promising Radiopharmaceutical Tracers for Detection of Cardiotoxicity in Cardio-oncology.","authors":"Zahra Shaghaghi,&nbsp;Fatemeh Jalali Zefrei,&nbsp;Arsalan Salari,&nbsp;Seyed Amineh Hojjati,&nbsp;Seyed Aboozar Fakhr Mousavi,&nbsp;Soghra Farzipour","doi":"10.2174/1874471016666230228102231","DOIUrl":"https://doi.org/10.2174/1874471016666230228102231","url":null,"abstract":"<p><p>Cancer treatment has the potential to cause cardiovascular issues and can encourage the appearance of all aspects of cardiac disease, including coronary heart disease, myocardial disease, heart failure, structural heart disease, and rhythm problems. Imaging is required for both diagnostic workup and therapy monitoring for all possible cardiovascular side effects of cancer therapy. Echocardiography is the cardiac imaging gold standard in cardio-oncology. Despite advancements in its use, this method is often not sensitive to early-stage or subclinical impairment. The use of molecular imaging technologies for diagnosing, assessing, and tracking cardiovascular illness as well as for treating, it is fast growing. Molecular imaging techniques using biologically targeted markers are gradually replacing the traditional anatomical or physiological approaches. They offer unique insight into patho-biological processes at the molecular and cellular levels and enable the evaluation and treatment of cardiovascular disease. This review paper will describe molecularbased single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging techniques that are now available and in development to assess post-infarction cardiac remodeling. These methods could be used to evaluate important biological processes such as inflammation, angiogenesis, and scar formation.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":"16 3","pages":"171-184"},"PeriodicalIF":2.3,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960885","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
An In-House 3D Voxel Dosimetric Tool to Compare Predictive and Post- Treatment Dosimetry in 90Y Radioembolization: A Proof of Concept. 一种内部3D体素剂量测定工具,用于比较90Y放射栓塞的预测和治疗后剂量测定:概念验证。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-05 DOI: 10.2174/1874471016666230215102455
Ornella Ferrando, Rossana Bampi, Franca Foppiano, Andrea Ciarmiello

Aim: The aim of this study was to implement an in-house dosimetric tool to assess tumour- absorbed doses in pre and post-dosimetry for 90Y radioembolization with resin spheres.

Materials and methods: To perform dosimetric calculations we set up a dosimetric procedure and developed homemade software to calculate tumour absorbed dose and dose volume histograms (DVHs). The method is based on a simplified voxel dosimetry for an estimated 3D absorbed dose and it can be applied to both 99mTc-MAA SPECT/CT and 90Y PET/CT acquisitions for pre and post-dosimetry. We tested the software performance in a retrospective study using the data of 22 patients with hepatocellular carcinoma who underwent radioembolization with 90Y resin spheres in the period 2016-2021. The software calculates tumour doses (mean, minimum and maximum doses) from voxel counts and dose-volume histograms (DVH_spect, DVH_pet) for both 99mTc-MAA SPECT/CT and 90Y PET/CT imaging. DVH_spect and DVH_pet data were analyzed and compared with the aim to assess an agreement between them. Concordance between dosimetric data were evaluated with the Wilcoxon Signed Ranked test, descriptive statistical analysis and Pearson correlation coefficient.

Results: The mean administrated activity was 1313 MBq (range 444 MBq - 2200 MBq). Tumour volumes ranged from 75 mL to 1012 mL. The mean absorbed dose for tumour volume was 161 ± 66 Gy (Dm_spect) and 173 ± 79 Gy (Dm_pet). From Wilcoxon Signed Rank Test the differences between the dosimetric data extrapolated from DVH_spect and DVH_pet results were not significant with α = 0.05 (two-sided test). A good linear correlation was found between 99mTc-MAA and 90Y dosimetric data (Pearson correlation coefficient 0.887 p < 0.001). Generally, DVHs calculated on 99mTc-MAA SPECT/CT and 90Y PET/CT gave comparable results, some discrepancies were observed particularly with those patients where SPECT and PET imaging presented a visual mismatching.

Conclusion: A simplified 3D dosimetry methodology was implemented and tested retrospectively on patient data treated with 90Y resin spheres. Even if the clinical feasibility of our approach has to be further validated on an extended patient cohort, the preliminary results of our study highlight the potential of the implemented dosimetric tool for tumour dose assessment.

目的:本研究的目的是实施一种内部剂量学工具,以评估树脂球90Y放射栓塞前和后剂量学中的肿瘤吸收剂量。材料和方法:为了进行剂量学计算,我们建立了一个剂量学程序,并开发了自制的软件来计算肿瘤吸收剂量和剂量体积直方图(DVHs)。该方法基于预估3D吸收剂量的简化体素剂量学,可应用于99mTc-MAA SPECT/CT和90Y PET/CT采集,用于剂量测定前后。我们在一项回顾性研究中测试了软件的性能,该研究使用了2016-2021年期间接受90Y树脂球放射栓塞治疗的22例肝细胞癌患者的数据。该软件计算肿瘤剂量(平均,最小和最大剂量)从体素计数和剂量-体积直方图(DVH_spect, DVH_pet)为99mTc-MAA SPECT/CT和90Y PET/CT成像。对DVH_spect和DVH_pet数据进行分析和比较,目的是评估两者之间的一致性。采用Wilcoxon sign ranking检验、描述性统计分析和Pearson相关系数评价剂量学资料的一致性。结果:平均给药活度为1313 MBq(范围为444 MBq - 2200 MBq)。肿瘤体积为75 ~ 1012 mL,肿瘤体积的平均吸收剂量为161±66 Gy (Dm_spect)和173±79 Gy (Dm_pet)。根据Wilcoxon sign Rank检验,DVH_spect和DVH_pet结果外推的剂量学数据差异无统计学意义,α = 0.05(双侧检验)。99mTc-MAA与90Y剂量学数据呈良好的线性相关(Pearson相关系数0.887 p < 0.001)。通常,在99mTc-MAA SPECT/CT和90Y PET/CT上计算的dvh结果相当,特别是在SPECT和PET成像出现视觉不匹配的患者中,观察到一些差异。结论:采用了一种简化的三维剂量学方法,并对90Y树脂球治疗的患者资料进行了回顾性测试。即使我们的方法的临床可行性还需要在更广泛的患者队列中进一步验证,我们研究的初步结果也强调了实施剂量学工具用于肿瘤剂量评估的潜力。
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引用次数: 0
World's First Experience of the Low-Dose Radionuclide Inhalation Therapy in the Treatment of COVID-19-Associated Viral Pneumonia: Phase 1/2 Clinical Trial. 低剂量放射性核素吸入治疗新型冠状病毒相关病毒性肺炎全球首例临床试验
IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-06-05 DOI: 10.2174/1874471016666230307113045
Peter Shegay, Alexey Leontyev, Denis Baranovskii, German Davydov, Marina Poluektova, Lyudmila Grivtsova, Vasily Petriev, Valeriy Stepanenko, Igor Gulidov, Valeriy Krylov, Svetlana Osadchaya, Vladimir Petrov, Maria Sedova, Mikhail Vekilyan, Olga Krasilnikova, Sergey Morozov, Sergey Ivanov, Ilya Klabukov, Andrey Kaprin

Objective: Previously, low-dose radiation therapy was used for pneumonia treatment. We aimed to investigate the safety and effectiveness of carbon nanoparticles labeled with Technetium isotope (99mTc) in a form of ultradispersed aerosol in combination with standard COVID-19 therapy. The study was a randomized phase 1 and phase 2 clinical trial of low-dose radionuclide inhalation therapy for patients with COVID-19 related pneumonia.

Methods: We enrolled 47 patients with confirmed COVID-19 infection and early laboratory signs of cytokine storm and randomized them into the Treatment and Control groups. We analyzed blood parameters reflecting the COVID-19 severity and inflammatory response.

Results: Low-dose 99mTc-labeled inhalation showed a minimal accumulation of radionuclide in lungs in healthy volunteers. We observed no significant differences between the groups before treatment in WBC-count, D-dimer, CRP, Ferritin or LDH levels. We found that Ferritin and LDH levels significantly raised after the 7th day follow-up only in the Control group (p < 0.0001 and p = 0.0005, respectively), while mean values of the same indicators did not change in patients in the Treatment group after the radionuclide treatment. D-dimer values also lowered in the radionuclide treated group, however, this effect was not statistically significant. Furthermore, we observed a significant decrease in CD19+ cell counts in patients of the radionuclide-treated group.

Conclusion: Inhalation low-dose radionuclide therapy of 99mTc aerosol affects the major prognostic indicators of COVID-19- related pneumonia restraining inflammatory response. Overall, we identified no evidence of major adverse events in the group receiving radionuclide.

目的:以前,低剂量放射治疗被用于肺炎的治疗。我们的目的是研究超分散气溶胶形式的锝同位素(99mTc)标记的碳纳米颗粒与标准COVID-19治疗联合使用的安全性和有效性。该研究是一项低剂量放射性核素吸入治疗COVID-19相关肺炎患者的随机1期和2期临床试验。方法:选取47例确诊为COVID-19感染并有细胞因子风暴早期实验室体征的患者,随机分为治疗组和对照组。我们分析了反映COVID-19严重程度和炎症反应的血液参数。结果:低剂量99mtc标记吸入显示,放射性核素在健康志愿者肺部的积累最小。我们观察到治疗前各组间白细胞计数、d -二聚体、CRP、铁蛋白或LDH水平无显著差异。我们发现,只有对照组患者在随访第7天后铁蛋白和LDH水平显著升高(p < 0.0001和p = 0.0005),而治疗组患者在放射性核素治疗后,这些指标的平均值没有变化。放射性核素处理组d -二聚体值也降低,但无统计学意义。此外,我们观察到放射性核素治疗组患者的CD19+细胞计数显著下降。结论:吸入低剂量放射性核素治疗99mTc气雾剂可影响COVID-19相关性肺炎的主要预后指标,抑制炎症反应。总的来说,我们没有发现在接受放射性核素治疗的人群中发生重大不良事件的证据。
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引用次数: 0
Preface 前言
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-01 DOI: 10.1109/DEEC.2005.18
A. Ciarmiello
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引用次数: 0
Re-Evaluation of Patient-Sourced Radiation Doses in PET/CT. PET/CT中患者源辐射剂量的再评估。
IF 2.3 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2174/1874471016666230102122554
Ahmet Murat Şenışık, Handan Tanyıldızı Kökkülünk, Mahmut Yüksel

Background: New generation PET/CT devices provide quality images using low radiopharmaceutical activities. Dose monitoring is carried out for nuclear medicine personnel, other health personnel, and companions by determining the radiation dose emitted from low-activity patients to the environment. In particular, it is necessary to revise the working conditions of the personnel according to the radiation dose exposed.

Aim: It was aimed to reevaluate the radiation dose rate transmitted to the environment from patients injected with 18F-FDG.

Materials and methods: A total of 31 patients (14F, 17M) who underwent 18F-FDG PET/CT imaging were included. The mean 18F-FDG activity of 7.26 ± 1.29 mCi was used for injection. After injection, radiation dose rates (mR/h) were measured at distances of 25, 50, 100, 150, and 200cm for 3 different periods from the level of the head, thorax, abdomen, and pelvis by using a GM counter. Additionally, biological samples such as urine and sweat were taken during 3 different periods. The activity amounts (μCi) in the samples were measured with a well-type counter.

Results: Strong correlations were calculated between normalized dose rates obtained by all regions and time. Considering the nuclear medicine staff handling time with a PET/CT patient, the average dose received by staff was calculated between a range of 0.002-0.004 mSv/pt. The radiation dose exposed to the porter and nurse was calculated as 0.049 mSv/pt for the 2nd hour and 0.001-0.007 mSv/pt for the 4th hour, respectively. The companion was exposed to a dose between 0.073-0.147 mSv and 0.024-0.048 mSv for public transport and private car transportation after 4-6 hours of injection (for 30-60 min of travel duration), respectively. For inpatients, the received dose for porters, serving 20min from a distance of 30cm for the 2nd and 4th hours after the PET/CT scan, was 0.049 mSv/pt and 0.048 mSv/pt, respectively. And for nurses serving from a 50cm distance between 1-5 minutes, these values were found to be 0.001-0.007mSv/pt, 0.001-0.007mSv/pt, and 0.001-0.006mSv/pt, respectively.

Conclusion: The radiation dose of nuclear medicine staff, porters, nurses, and companions are found to be below the recommended dose limit by the ICRP. According to our results, there is no need for any restrictions for patients, companions, or healthcare personnel in PET/CT units.

背景:新一代PET/CT设备使用低放射性药物活性提供高质量的图像。对核医学人员、其他卫生人员和随行人员进行剂量监测,确定低活度患者向环境释放的辐射剂量。特别是,有必要根据暴露的辐射剂量修改人员的工作条件。目的:重新评价注射18F-FDG患者对环境的辐射剂量率。材料和方法:共纳入31例(14F, 17M)行18F-FDG PET/CT成像的患者。注射用18F-FDG平均活度为7.26±1.29 mCi。注射后,使用GM计数器在距头、胸、腹、骨盆水平25、50、100、150、200cm的3个不同时段测量辐射剂量率(mR/h)。此外,在3个不同时期采集尿液和汗液等生物样本。用孔式计数器测定样品的活度(μCi)。结果:各地区得到的归一化剂量率与时间有很强的相关性。考虑到核医学工作人员与PET/CT患者接触的时间,计算出工作人员接受的平均剂量在0.002-0.004 mSv/pt之间。搬运工和护士第2小时和第4小时的辐射剂量分别为0.049 mSv/pt和0.001-0.007 mSv/pt。在公共交通和私家车上,同伴在注射后4-6小时(旅行时间30-60分钟)分别受到0.073-0.147毫西弗和0.024-0.048毫西弗的剂量。对于住院患者,搬运工在PET/CT扫描后第2小时和第4小时,在距离30cm的20分钟内接受的剂量分别为0.049 mSv/pt和0.048 mSv/pt。对于在1-5分钟之间50厘米距离内服务的护士,这些值分别为0.001-0.007mSv/pt, 0.001-0.007mSv/pt和0.001-0.006mSv/pt。结论:核医学工作人员、搬运工、护士及随行人员的辐射剂量均低于ICRP推荐剂量限值。根据我们的研究结果,无需对PET/CT病房的患者、陪伴者或医护人员进行任何限制。
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引用次数: 0
期刊
Current radiopharmaceuticals
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