Journal of labelled compounds & radiopharmaceuticals最新文献_第5页

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

Synthesis of [3H]Org24598 using in-house prepared [3H]MeI 使用内部制备的[3 H]MeI 合成[3 H]Org24598 。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-01-14 DOI: 10.1002/jlcr.4084

Michal Kriegelstein, Gabriela Nováková, Aleš Marek

引用次数: 0

Preparation of [1′-13C]citric acid as a probe in a breath test to evaluate tricarboxylic acid cycle flux 制备[1'-13 C]柠檬酸作为呼气试验的探针，以评估三羧酸循环通量。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-01-03 DOI: 10.1002/jlcr.4083

Hidemichi Mitome, Mieko Takenishi, Kumiko Ono, Naoyuki Kawagoe, Tsunehiko Imai, Yosuke Sasaki, Yoshihisa Urita, Kazuki Akira

引用次数: 0

A facile synthesis of precursor for the σ-1 receptor PET radioligand [18F]FTC-146 and its radiofluorination σ-1受体PET放射性配体[18 F]FTC-146 前体的简易合成及其放射性氟化。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-01-03 DOI: 10.1002/jlcr.4081

Anna Marešová, Michal Jurášek, Pavel B. Drašar, Bohumil Dolenský, Elena A. Prokudina, Vladimir Shalgunov, Matthias M. Herth, Paul Cumming, Alexander Popkov

{"title":"A facile synthesis of precursor for the σ-1 receptor PET radioligand [18F]FTC-146 and its radiofluorination","authors":"Anna Marešová, Michal Jurášek, Pavel B. Drašar, Bohumil Dolenský, Elena A. Prokudina, Vladimir Shalgunov, Matthias M. Herth, Paul Cumming, Alexander Popkov","doi":"10.1002/jlcr.4081","DOIUrl":"10.1002/jlcr.4081","url":null,"abstract":"The σ-1 receptor is a non-opioid transmembrane protein involved in various human pathologies including neurodegenerative diseases, inflammation, and cancer. The previously published ligand [18F]FTC-146 is among the most promising tools for σ-1 molecular imaging by positron emission tomography (PET), with a potential for application in clinical diagnostics and research. However, the published six- or four-step synthesis of the tosyl ester precursor for its radiosynthesis is complicated and time-consuming. Herein, we present a simple one-step precursor synthesis followed by a one-step fluorine-18 labeling procedure that streamlines the preparation of [18F]FTC-146. Instead of a tosyl-based precursor, we developed a one-step synthesis of the precursor analog AM-16 containing a chloride leaving group for the SN2 reaction with 18F-fluoride. 18F-fluorination of AM-16 led to a moderate decay-corrected radiochemical yield (RCY = 7.5%) with molar activity (Am) of 45.9 GBq/μmol. Further optimization of this procedure should enable routine radiopharmaceutical production of this promising PET tracer.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 2","pages":"59-66"},"PeriodicalIF":1.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087222","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

Open-source flow setup for rapid and efficient [18F]fluoride drying for automation of PET tracer syntheses 用于快速高效[18 F]氟化物干燥的开源流程设置，实现 PET 示踪剂合成自动化。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-12-28 DOI: 10.1002/jlcr.4080

Florian Menzel, Jonathan Cotton, Thomas Ziegler, Andreas Maurer, Jochen M. Neumaier

{"title":"Open-source flow setup for rapid and efficient [18F]fluoride drying for automation of PET tracer syntheses","authors":"Florian Menzel, Jonathan Cotton, Thomas Ziegler, Andreas Maurer, Jochen M. Neumaier","doi":"10.1002/jlcr.4080","DOIUrl":"10.1002/jlcr.4080","url":null,"abstract":"One of the key strategies for radiochemical research facilities is the automation of synthesis processes. Unnecessary manual operations increase the radiation exposure of personnel, while simultaneously threatening the reliability of syntheses. We have previously reported an affordable open-source system comprising 3D-printed continuous flow reactors, a custom syringe pump, and a pressure regulator that can be used to perform radiofluorinations. In this paper, we address additional essential processes that are needed for radiotracer development and synthesis, with the aim of making laboratory work safer and research more efficient. We have designed and evaluated a fully automated system for rapidly and effectively processing and drying aqueous [18F]fluoride that can be directly connected to the cyclotron. This process relies on triflyl fluoride gas generation and allows nucleophilic [18F]fluoride to be prepared safely in a hotcell within 10 min and an activity recovery of 91.7 ± 1.6% (n = 5). Owing to the need for convenient radiofluorinated prosthetic ligands, we have adapted our continuous flow system to produce [18F]fluoroethyl tosylate (FEOTs) and [18F]fluoroethyl triflate (FEOTf), prosthetic groups that are widely used for late-stage fluoroethylation of PET tracers. The processes as well as the radiolabeling of different groups are compared and comprehensively discussed. Having a method providing [18F]fluoroethyl tosylate (FEOTs) as well as [18F]fluoroethyl triflate (FEOTf) quickly and highly efficiently is beneficial for radiochemical research.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 2","pages":"40-58"},"PeriodicalIF":1.8,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058439","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

Development of radiotracers for riboflavin transporter 3 imaging in diseases—A brief overview 用于核黄素转运体 3 在疾病中成像的放射性racers 的开发--简述。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-12-22 DOI: 10.1002/jlcr.4076

Jindian Li, Xianzhong Zhang

引用次数: 0

Automated radiosynthesis of [18F]CETO, a PET radiotracer for imaging adrenal glands, on Synthra RNplus 用于肾上腺成像的 PET 放射性示踪剂 [18 F]CETO 在 Synthra RNplus 上的自动放射合成。

IF 1.8 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-12-20 DOI: 10.1002/jlcr.4078

Matthew Hird, Joseph J. Russell, Lei Li Corrigan, Istvan Boros, Patrik Nordeman, Gunnar Antoni, Mark Gurnell, Franklin I. Aigbirhio

{"title":"Automated radiosynthesis of [18F]CETO, a PET radiotracer for imaging adrenal glands, on Synthra RNplus","authors":"Matthew Hird, Joseph J. Russell, Lei Li Corrigan, Istvan Boros, Patrik Nordeman, Gunnar Antoni, Mark Gurnell, Franklin I. Aigbirhio","doi":"10.1002/jlcr.4078","DOIUrl":"10.1002/jlcr.4078","url":null,"abstract":"Primary aldosteronism (PA) is the leading secondary cause of hypertension. Determining whether one (unilateral) or both (bilateral) adrenal glands are the source of PA in a patient remains challenging, and yet it is a critical step in the decision whether to recommend potentially curative surgery (adrenalectomy) or lifelong medical therapy (typically requiring multiple drugs). Recently, we have developed a fluorine-18 radiopharmaceutical [18F]CETO to permit greater access to PA molecular imaging. Herein, we report an automated synthesis of this radiotracer. To manufacture the radiopharmaceutical routinely for clinical PET studies, we implemented an automated radiosynthesis method on a Synthra RNplus© synthesiser for which Cl-tosyletomidate was used as the precursor for radiolabelling via nucleophilic [18F]fluorination. [18F]CETO was produced with 35 ± 1% (n = 7), decay corrected and 25 ± 4% (n = 7) non-decay corrected radiochemical yield with molar activities ranging from 150 to 400 GBq/μmol. The GMP compliant manufacturing process produces a sterile formulated [18F]CETO injectable solution for human use as demonstrated by the results of quality control. Automation of the radiosynthesis of [18F]CETO should facilitate uptake by other adrenal centres and increase access to molecular imaging in PA.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 2","pages":"67-75"},"PeriodicalIF":1.8,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138806677","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