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.
{"title":"Preclinical Aspects of [89Zr]Zr-DFO-Rituximab: A High Potential Agent for Immuno-PET Imaging.","authors":"Zahra Rouhollahi, Seyed Mahmoud Reza Aghamiri, Hassan Yousefnia, Behrouz Alirezapour, Ali Moghaddasi, Samaneh Zolghadri","doi":"10.2174/0118744710326742241018050220","DOIUrl":"https://doi.org/10.2174/0118744710326742241018050220","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>[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.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496720","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}
<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
{"title":"Enhancing Ketoprofen Solubility: A Strategic Approach Using Solid Dispersion and Response Surface Methodology.","authors":"Devika Tripathi, Dinesh Kumar Sharma, Jagannath Sahoo","doi":"10.2174/0118744710311951241018054453","DOIUrl":"https://doi.org/10.2174/0118744710311951241018054453","url":null,"abstract":"<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","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496719","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}
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。
{"title":"Apigenin's Influence on Inflammatory and Epigenetic Responses in Rat Lungs After Radiotherapy.","authors":"Fatemeh Rajabinasab, Pooya Hajimirzaei, Fatemeh Ramezani, Fariborz Moayer, Fazel Gorjipour, Alireza Nikoofar, Leila Hasanzadeh, Michael R Hamblin, Atousa Janzadeh, Reza Paydar","doi":"10.2174/0118744710336823241011095632","DOIUrl":"https://doi.org/10.2174/0118744710336823241011095632","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Api administration mitigated radiation-induced lung damage by reversing inflammatory and epigenetic changes.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496718","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}
Pub Date : 2024-09-02DOI: 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.
{"title":"An Analysis of the Radiosensitiser Applications in the Biomedical Field.","authors":"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","doi":"10.2174/0118744710269842240825160247","DOIUrl":"https://doi.org/10.2174/0118744710269842240825160247","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Results and conclusion: </strong>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.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119212","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}
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.
{"title":"Left Ventricular Wall Motion as an Additional Valuable Parameter in Diabetic Patients with Normal Myocardial Perfusion Imaging.","authors":"Amirhesam Davari, Fatemeh Jalali-Zefrei, Bahareh Gholami-Chabok, Shiva Tabaghi, Soghra Farzipour, Kourosh Delpasand, Seyed Mehdi Mousavi","doi":"10.2174/0118744710312688240814100448","DOIUrl":"https://doi.org/10.2174/0118744710312688240814100448","url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281760","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}
Pub Date : 2024-07-22DOI: 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
{"title":"Pressed Solid Target Production of 89Zr and its Application for Antibody Labelling.","authors":"Anjli Shrivastav, Sonu Maurya, Manish Dixit, Sarita Kumari, Sanjay Gambhir","doi":"10.2174/0118744710318544240715061530","DOIUrl":"https://doi.org/10.2174/0118744710318544240715061530","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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</p>.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747686","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}
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.
{"title":"Recent Advances in the Diagnosis of Alzheimer's Disease: A Brief Overview of Tau PET Tracers in Nuclear Medicine.","authors":"Farahnaz Aghahosseini, Yalda Salehi, Saeed Farzanefar, Mohsen Bakhshi Kashi, Elisabeth Eppard, Hojjat Ahmadzadehfar, Siroos Mirzaei, Nasim Vahidfar, Ayuob Aghanejad","doi":"10.2174/0118744710314668240718070109","DOIUrl":"https://doi.org/10.2174/0118744710314668240718070109","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747687","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}
Pub Date : 2024-04-30DOI: 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.
{"title":"Biological Efficacy of Ionizing Radiation Sources on 3D Organotypic Tissue Slices Assessed by Fluorescence Microscopy.","authors":"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","doi":"10.2174/0118744710293570240419110322","DOIUrl":"https://doi.org/10.2174/0118744710293570240419110322","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Biological dosimetry is represented by differentially stained 200-µm thick organotypic tissue sections related to living and dead cells and cell metabolic activity.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862297","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}
Pub Date : 2024-04-29DOI: 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.
{"title":"Radiopharmaceuticals Adverse Events Management.","authors":"Ana Agudo Martínez, Gertrudis Sabatel Hernandez, Manuela Molina Mora, Pablo Antonio de la Riva Perez, Rosa Fernandez Lopez, Teresa Cambil Molina, Cinta Calvo Moron","doi":"10.2174/0118744710284298240419115911","DOIUrl":"https://doi.org/10.2174/0118744710284298240419115911","url":null,"abstract":"<p><strong>Background and purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854634","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}
Pub Date : 2024-04-22DOI: 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.
{"title":"Guideline Adherence as an Indicator of PET Scan Overuse in an Italian Teaching Hospital: An Observational Study.","authors":"Giuseppe Lucio Cascini, Marianna Mauro, Barbara Catalfamo, Monica Giancotti, Roberta Muraca","doi":"10.2174/0118744710290906240408094829","DOIUrl":"https://doi.org/10.2174/0118744710290906240408094829","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>Analysis showed a not complete adherence to national guidelines and no shared decision-making approach.</p>","PeriodicalId":10991,"journal":{"name":"Current radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876128","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}