Journal of labelled compounds & radiopharmaceuticals最新文献_第3页

Synthesis of Deuterated Endochin-Like Quinolones 氘代内脏类喹诺酮的合成。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-04-25 DOI: 10.1002/jlcr.4092

Sovitj Pou, Rolf W. Winter, Katherine M. Liebman, Rosie A. Dodean, Aaron Nilsen, Andrea DeBarber, J. Stone Doggett, Michael K. Riscoe

引用次数: 0

An Improved HPLC Separation Method for TSPO Radioligand [11C]ER176 Clinical Production 一种用于 TSPO 放射性配体 [11C]ER176 临床生产的改进型 HPLC 分离方法

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-04-19 DOI: 10.1002/jlcr.4093

Kang-Po Li, Hancheng Cai

{"title":"An Improved HPLC Separation Method for TSPO Radioligand [11C]ER176 Clinical Production","authors":"Kang-Po Li, Hancheng Cai","doi":"10.1002/jlcr.4093","DOIUrl":"10.1002/jlcr.4093","url":null,"abstract":"<div>\u0000 \u0000 Mitochondrial membrane translocator protein 18 kDa (TSPO) expression is increased in activated microglia, established as a plausible target of neuroinflammation imaging. [11C]ER176, specifically binding to TSPO, has been developed as the third generation of radioligand for PET imaging of TSPO, which showed the potential in better quantifying neuroinflammation than its predecessors. In the current study, we developed an automated radiosynthesis with an improved HPLC purification method for [11C]ER176 clinical production. The improved HPLC separation was integrated into the automated production of [11C]ER176 using a reverse phase semi-preparative HPLC column with an isocratic pump and the mixture of methanol and 50 mM ammonium acetate as the mobile phase. The fraction corresponding to [11C]ER176 was collected around 8.5–9.0 min without the risk of getting contaminations from nearby impurities. The automated production process took about 30 min after end of bombardment (EOB) and the quality of the final product [11C]ER176 met all specifications for clinical use based on current US Pharmacopeia and FDA CGMP requirements.\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 7","pages":"273-276"},"PeriodicalIF":1.8,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626778","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

Carbon 14 and Carbon 13 Syntheses of Velagliflozin 碳 14 和碳 13 合成 Velagliflozin

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-04-11 DOI: 10.1002/jlcr.4091

Bachir Latli, Matt J. Hrapchak, Maxim Chevliakov, Chutian Shu

引用次数: 0

Preparation, Characterization, and Radiolabeling of Anti-HER2 scFv With Technetium Tricarbonyl and Stability Studies 三羰基锝抗 HER2 scFv 的制备、表征、放射性标记及稳定性研究

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-03-14 DOI: 10.1002/jlcr.4090

Negar Bozorgchami, Maryam Ahmadzadeh, Dara Hatamabadi, Abdolreza Yazdani, Soraya Shahhosseini, Elham Mohit

{"title":"Preparation, Characterization, and Radiolabeling of Anti-HER2 scFv With Technetium Tricarbonyl and Stability Studies","authors":"Negar Bozorgchami, Maryam Ahmadzadeh, Dara Hatamabadi, Abdolreza Yazdani, Soraya Shahhosseini, Elham Mohit","doi":"10.1002/jlcr.4090","DOIUrl":"10.1002/jlcr.4090","url":null,"abstract":"<div>\u0000 \u0000 Breast cancer is the most common diagnosed cancer, and the second cause of cancer death among women, worldwide. HER2 overexpression occurred in approximately 15% to 20% of breast cancers. Invasive biopsy method has been used for detection of HER2 overexpression. HER2-targeted imaging via an appropriate radionuclide is a promising method for sensitive and accurate identification of HER2+ primary and metastatic lesions. 99mTc-anti-HER2 scFv can specifically target malignancies and be used for diagnosis of the cancer type and metastasis as well as treatment of breast cancer. We radiolabeled anti-HER2 scFv that was expressed in Escherichia coli and purified through Ni-NTA resin under native condition with 99mTc-tricarbonyl formed from boranocarbonate. HER2-based ELISA, BCA, TLC, and HPLC were used in this study. In the current study, anti-HER2 scFv was lyophilized before radiolabeling. It was found that freeze-drying did not change the binding activity of anti-HER2 scFv to HER2. Results demonstrated direct anti-HER2 scFv radiolabeling by 99mTc-tricarbonyl to hexahistidine sequence (His-tag) without any changes in biological activity and radiochemical purity of around 98%. Stability analysis revealed that 99mTc-anti-HER2 scFv is stable for at least 24 h in PBS buffer, normal saline, human plasma proteins, and histidine solution.\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 5","pages":"168-179"},"PeriodicalIF":1.8,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131749","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

Synthesis of Stable Isotope, Tritiated, and Carbon-14 Labeled Balcinrenone 合成稳定同位素、三联苯和碳-14 标记的 Balcinrenone。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-03-05 DOI: 10.1002/jlcr.4089

Jonas Bergare, Christopher Bailey, Henrik Sörensen, Gunnar Grönberg, Karl Broberg, Monica Berglund, Tudor Grecu, Carolina Sanchez, Hans Emtenäs, Ryan A. Bragg, Charles S. Elmore

引用次数: 0

Automated radiosynthesis of mGluR5 PET tracer [18F]FPEB from aryl-chloro precursor and validation for clinical application 从芳基氯前驱体中自动放射性合成 mGluR5 PET 示踪剂 [18 F]FPEB 并进行临床应用验证。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-02-19 DOI: 10.1002/jlcr.4088

Mahabuba Jahan, Arsalan Amir, Arindam Das, Jacob Kihlström, Sangram Nag

{"title":"Automated radiosynthesis of mGluR5 PET tracer [18F]FPEB from aryl-chloro precursor and validation for clinical application","authors":"Mahabuba Jahan, Arsalan Amir, Arindam Das, Jacob Kihlström, Sangram Nag","doi":"10.1002/jlcr.4088","DOIUrl":"10.1002/jlcr.4088","url":null,"abstract":"The radioligand [18F]FPEB, used for PET imaging of the brain's metabotropic glutamate receptor subtype 5 (mGluR5), undergoes a thorough validation process to ensure its safety, efficacy, and quality for clinical use. The process starts by optimizing the synthesis of [18F]FPEB to achieve high radiochemical yield and purity. This study focuses on optimizing the radiolabeling process using an aryl-chloro precursor and validating the GMP production for clinical applications. Fully automated radiolabeling was achieved via one-step nucleophilic substitution reaction. [18F]FPEB was produced and isolated in high radioactivity and radiochemical purity. Throughout the validation process, thorough quality control measures are implemented. Radiopharmaceutical batch release criteria are established, including testing for physical appearance, filter integrity, pH, radiochemical purity, molar activity, radiochemical identity, chemical impurity, structural identity, stability, residual solvent, sterility, and endotoxin levels. In conclusion, the validation of [18F]FPEB involved a comprehensive process of synthesis optimization, quality control, which ensure the safety, efficacy, and quality of [18F]FPEB, enabling its reliable use in clinical PET. Here, we successfully radiolabeled and validated [18F]FPEB using aryl-chloro precursor according to GMP production for clinical application.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 4","pages":"155-164"},"PeriodicalIF":1.8,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139900100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Formulation of patient dose of [177Lu]Lu-Trastuzumab using in-house developed freeze-dried kit: A path forward for clinical translation 使用自主研发的冻干试剂盒配制患者剂量的[177 Lu]Lu-曲妥珠单抗：临床转化之路。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-02-11 DOI: 10.1002/jlcr.4086

Jeyachitra Amirdhanayagam, Mohini Guleria, Rohit Sharma, Naveen Kumar, Archana Mukherjee, Tapas Das

{"title":"Formulation of patient dose of [177Lu]Lu-Trastuzumab using in-house developed freeze-dried kit: A path forward for clinical translation","authors":"Jeyachitra Amirdhanayagam, Mohini Guleria, Rohit Sharma, Naveen Kumar, Archana Mukherjee, Tapas Das","doi":"10.1002/jlcr.4086","DOIUrl":"10.1002/jlcr.4086","url":null,"abstract":"Trastuzumab is a US-FDA-approved humanized monoclonal antibody used for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The aim of the present work is to optimize a freeze-dried formulation of DOTA-Trastuzumab conjugate for the preparation of patient doses of [177Lu]Lu-Trastuzumab for radioimmunotherapy of breast cancer. The formulation of [177Lu]Lu-Trastuzumab usually takes a long time, and thus, such a process is not suitable for the routine preparation of this agent in hospital radiopharmacies. To circumvent this, a pre-synthesized DOTA-Trastuzumab conjugate as a freeze-dried formulation is proposed. In the present work, DOTA-Trastuzumab conjugate was subjected to a freeze-drying process after the addition of optimized amounts of radioprotectant and cryoprotectant. [177Lu]Lu-DOTA-Trastuzumab was prepared by incubating the lyophilized powder of the kit vial with medium-specific activity 177LuCl3. The final radiochemical purity of [177Lu]Lu-DOTA-Trastuzumab, prepared using freeze-dried kit, was determined to be >95%. To ascertain the reproducibility of the procedure, six consecutive batches of the freeze-dried formulation were prepared, radiolabeled, and evaluated by carrying out both in vitro and ex vivo studies. The consistency of the results of all the six consecutive batches confirmed the robustness and utility of the in-house optimized freeze-dried formulation for the preparation of patient doses of [177Lu]Lu-Trastuzumab at hospital radiopharmacies.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 4","pages":"131-144"},"PeriodicalIF":1.8,"publicationDate":"2024-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139717618","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

Tritium and deuterium labelling of a kainate receptor antagonist and evaluation as a radioligand 一种凯纳特受体拮抗剂的氚和氘标记以及作为放射性配体的评估。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-02-08 DOI: 10.1002/jlcr.4087

Paulina Chałupnik, Aleš Marek, Marie Emilie Leiticia Hovah, Darryl S. Pickering, Piero Temperini, Stephanie Donbosco, Ewa Szymańska, Tommy N. Johansen

{"title":"Tritium and deuterium labelling of a kainate receptor antagonist and evaluation as a radioligand","authors":"Paulina Chałupnik, Aleš Marek, Marie Emilie Leiticia Hovah, Darryl S. Pickering, Piero Temperini, Stephanie Donbosco, Ewa Szymańska, Tommy N. Johansen","doi":"10.1002/jlcr.4087","DOIUrl":"10.1002/jlcr.4087","url":null,"abstract":"Kainate receptors play a crucial role in mediating synaptic transmission within the central nervous system. However, the lack of selective pharmacological tool compounds for the GluK3 subunit represents a significant challenge in studying these receptors. Recently presented compound 1 stands out as a potent antagonist of GluK3 receptors, exhibiting nanomolar affinity at GluK3 receptors and strongly inhibiting glutamate-induced currents at homomeric GluK1 and GluK3 receptors in HEK293 cells with Kb values of 65 and 39 nM, respectively. This study presents the synthesis of two potent GluK3-preferring iodine derivatives of compound 1, serving as precursors for radiolabelling. Furthermore, we demonstrate the optimisation of dehalogenation conditions using hydrogen and deuterium, resulting in [2H]-1, and demonstrate the efficient synthesis of the radioligand [3H]-1 with a specific activity of 1.48 TBq/mmol (40.1 Ci/mmol). Radioligand binding studies conducted with [3H]-1 as a radiotracer at GluK1, GluK2, and GluK3 receptors expressed in Sf9 and rat P2 membranes demonstrated its potential applicability for selectively studying native GluK3 receptors in the presence of GluK1 and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-blocking ligands.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 4","pages":"120-130"},"PeriodicalIF":1.8,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Automated radiolabeling and handling of 177Lu- and 225Ac-PSMA-617 using a robotic pipettor 使用机器人移液器自动对 177 Lu- 和 225 Ac-PSMA-617 进行放射性标记和处理。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-01-31 DOI: 10.1002/jlcr.4085

Shin Hye Ahn, Anthony P. Belanger

{"title":"Automated radiolabeling and handling of 177Lu- and 225Ac-PSMA-617 using a robotic pipettor","authors":"Shin Hye Ahn, Anthony P. Belanger","doi":"10.1002/jlcr.4085","DOIUrl":"10.1002/jlcr.4085","url":null,"abstract":"While automated modules for F-18 and C-11 radiosyntheses are standardized with features such as multiple reactors, vacuum connection and semi-preparative HPLC, labeling and processing of compounds with radiometals such as Zr-89, Lu-177 and Ac-225 often do not require complex manipulations and are frequently performed manually by a radiochemist. These procedures typically involve transferring solutions to and from vials using pipettes followed by heating of the reaction mixture, and do not require all the features found in most commercial automated synthesis units marketed as F-18 or C-11 modules. Here we present an efficient automated method for performing radiosyntheses involving radiometals by adapting a commercially available robotic pipettor originally developed for high-throughput processing of biological samples. While a robotic pipettor is less costly than a radiosynthesis module, it holds many similar advantages over manual radiosynthesis such as minimization of operator error, lower operator exposure rates, and abbreviated synthesis times, among others. To demonstrate the feasibility of using the OpenTrons OT-2 robotic pipettor to perform automated radiosyntheses, we radiolabeled and formulated 177Lu-PSMA-617 and 225Ac-PSMA-617 on the system. The OT-2 was then used to help streamline the quality control process for both products, further minimizing manual handling by and exposure to the radiochemist.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 3","pages":"111-115"},"PeriodicalIF":1.8,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

18F-Fluorination of a supported 2-(aryl-di-tert-butylsilyl)-N-methyl-imidazole for indirect 18F-labeling of a VHH single-variable domain 用于 VH H 单变量结构域间接 18 F 标记的 2-（芳基-二叔丁基硅基）-N-甲基咪唑的 18 F-氟化。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-01-15 DOI: 10.1002/jlcr.4082

Marine Steffann, Guillaume Bluet, Sébastien Roy, Catherine Aubert, Eric Fouquet, Philippe Hermange

引用次数: 0