Journal of labelled compounds & radiopharmaceuticals最新文献_第6页

Improved Radiosynthesis and Automation of [11C]2-(2,6-Difluoro-4-((2-(N-methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([11C]K2) for Positron Emission Tomography of the Glutamate α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid (AMPA) Receptor 改进[11C]2-(2,6-二氟-4-((2-(N-甲基苯基磺酰胺基)乙基)硫)苯氧基)乙酰胺（[11C]K2）的放射合成和自动化，用于谷氨酸α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体的正电子发射断层成像。

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-06-06 DOI: 10.1002/jlcr.4113

Jason A. Witek, Mami Horikawa, Bradford D. Henderson, Allen F. Brooks, Peter J. H. Scott, Xia Shao

{"title":"Improved Radiosynthesis and Automation of [11C]2-(2,6-Difluoro-4-((2-(N-methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([11C]K2) for Positron Emission Tomography of the Glutamate α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid (AMPA) Receptor","authors":"Jason A. Witek, Mami Horikawa, Bradford D. Henderson, Allen F. Brooks, Peter J. H. Scott, Xia Shao","doi":"10.1002/jlcr.4113","DOIUrl":"10.1002/jlcr.4113","url":null,"abstract":"A new automated radiosynthesis of [11C]2-(2,6-difluoro-4-((2-(N-methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([11C]K2), a radiopharmaceutical for the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, is reported. Although manual syntheses have been described, these are unsuitable for routine production of larger batches of [11C]K2 for (pre)clinical PET imaging applications. To meet demands for the imaging agent from our functional neuroimaging collaborators, herein, we report a current good manufacturing practice (cGMP)-compliant synthesis of [11C]K2 using a commercial synthesis module. The new synthesis is fully automated and has been validated for clinical use. The total synthesis time is 33 min from end of bombardment, and the production method provides 2.66 ± 0.3 GBq (71.9 ± 8.6 mCi) of [11C]K2 in 97.7 ± 0.5% radiochemical purity and 754.1 ± 231.5 TBq/mmol (20,382.7 ± 6256.1 Ci/mmol) molar activity (n = 3). Batches passed all requisite quality control testing confirming suitability for clinical use.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 9","pages":"324-329"},"PeriodicalIF":0.9,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283935","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

Synthesis and Evaluation of a Cathepsin B–Recognizing Trifunctional Chelating Agent to Improve Tumor Retention of Radioimmunoconjugates 合成和评估可识别 Cathepsin B 的三官能螯合剂，以改善放射免疫共轭物对肿瘤的保留。

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-06-05 DOI: 10.1002/jlcr.4112

Hiroki Jinda, Kazuma Nakashima, Hiroyuki Watanabe, Masahiro Ono

{"title":"Synthesis and Evaluation of a Cathepsin B–Recognizing Trifunctional Chelating Agent to Improve Tumor Retention of Radioimmunoconjugates","authors":"Hiroki Jinda, Kazuma Nakashima, Hiroyuki Watanabe, Masahiro Ono","doi":"10.1002/jlcr.4112","DOIUrl":"10.1002/jlcr.4112","url":null,"abstract":"<div>\u0000 \u0000 Cathepsin B (CTSB) is a lysosomal protease that is overexpressed in tumor cells. Radioimmunoconjugates (RICs) composed of CTSB-recognizing chelating agents are expected to increase the molecular weights of their radiometabolites by forming conjugates with CTSB in cells, resulting in their improved retention in tumor cells. We designed a novel CTSB-recognizing trifunctional chelating agent, azide-[111In]In-DOTA-CTSB-substrate ([111In]In-ADCS), to synthesize a RIC, trastuzumab-[111In]In-ADCS ([111In]In-TADCS), and evaluated its utility to improve tumor retention of the RIC. [111In]In-ADCS and [111In]In-TADCS were synthesized with satisfactory yield and purity. [111In]In-ADCS was markedly stable in murine plasma until 96 h postincubation. [111In]In-ADCS showed binding to CTSB in vitro, and the conjugation was blocked by the addition of CTSB inhibitor. In the internalization assay, [111In]In-TADCS exhibited high-level retention in SK-OV-3 cells, indicating the in vitro utility of the CTSB-recognizing unit. In the biodistribution assay, [111In]In-TADCS showed high-level tumor accumulation, but the retention was hardly improved. In the first attempt to combine a CTSB-recognizing unit and RIC, these findings show the fundamental properties of the CTSB-recognizing trifunctional chelating agent to improve tumor retention of RICs.\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 8","pages":"295-304"},"PeriodicalIF":0.9,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261660","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 Labeling Synthesis of RORγt Inhibitor JNJ-61803534 RORγt 抑制剂 JNJ-61803534 的碳 14 标记合成。

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-05-27 DOI: 10.1002/jlcr.4114

Fengbin Song, Rhys Salter, Lu Chen

引用次数: 0

Improving Routine 89Zr-Immuno-PET Applications: Mild Iron Removal Can Favor the Use of Fe-DFO-N-suc-TFP Ester Over p-NCS-Bz-DFO 改进 89Zr-Immuno-PET 的常规应用：轻度除铁有利于使用 Fe-DFO-N-suc-TFP 酯而不是 p-NCS-Bz-DFO。

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-05-14 DOI: 10.1002/jlcr.4097

Thomas E. Wuensche, Sabine Nauta, Guus A. M. S. van Dongen, Danielle J. Vugts

{"title":"Improving Routine 89Zr-Immuno-PET Applications: Mild Iron Removal Can Favor the Use of Fe-DFO-N-suc-TFP Ester Over p-NCS-Bz-DFO","authors":"Thomas E. Wuensche, Sabine Nauta, Guus A. M. S. van Dongen, Danielle J. Vugts","doi":"10.1002/jlcr.4097","DOIUrl":"10.1002/jlcr.4097","url":null,"abstract":"A key aspect for the applicability of 89Zr-radioimmunoconjugates is inert modification and radiolabeling. The two commercially available bifunctional variants of the siderophore desferrioxamine (DFO), Fe-DFO-N-suc-TFP-ester and p-NCS-Bz-DFO, are most often used for clinical 89Zr-immuno-PET. The use of Fe-DFO-N-suc-TFP-ester is advantageous with regard to higher radiolysis stability and more facile assessment of radiochemical purity as well as chelator-to-mAb ratio. However, not all mAbs withstand the Fe-removal step at relatively low pH (4–4.5) using EDTA, which is needed after conjugation to allow 89Zr labeling. In this study, it was investigated whether hydroxybenzyl ethylenediamine (HBED) or the clinically approved deferiprone (DFP) can serve as an alternative for EDTA to establish a pH-independent mild method for Fe-removal and thereby broaden the applicability of Fe-DFO-N-suc-TFP-ester. Carrier-added [59Fe]Fe-DFO-N-suc-TFP-ester was used for mAb modification to enable direct tracking of the Fe-removal efficiency under various conditions. Whereas incomplete Fe-removal with HBED was observed at pH 5 or higher, Fe-removal with DFP was possible at a broad pH range (4–9). This provides a mild, pH-independent method for Fe-removal, improving the applicability and attractiveness of Fe-DFO-N-suc-TFP-ester for 89Zr-mAb preparation.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 8","pages":"280-287"},"PeriodicalIF":0.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922445","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

Synthesis of Radiolabeled [14C]Rimsulfuron and Stable Isotope Labeled Rimsulfuron-[M + 3] to Support Crop Metabolism Studies for Reregistration 合成放射性标记的[14C]嘧磺隆和稳定同位素标记的嘧磺隆[M + 3]，以支持重新登记的作物代谢研究。

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-05-06 DOI: 10.1002/jlcr.4096

Lindsey G. Horty, Timothy Martin

{"title":"Synthesis of Radiolabeled [14C]Rimsulfuron and Stable Isotope Labeled Rimsulfuron-[M + 3] to Support Crop Metabolism Studies for Reregistration","authors":"Lindsey G. Horty, Timothy Martin","doi":"10.1002/jlcr.4096","DOIUrl":"10.1002/jlcr.4096","url":null,"abstract":"<div>\u0000 \u0000 Rimsulfuron is a sulfonylurea herbicide that controls grass and broadleaf weeds in maize, potatoes, fruits, nuts, and other crops. It can also be used as a burndown herbicide to clear invasive weed species along roadsides and other nonagricultural land. Rimsulfuron acts as an acetolactase synthase (ALS) inhibitor, blocking the synthesis of essential amino acids required for plant growth. As is common practice, rimsulfuron has been subject to periodic reviews by regulatory agencies for reregistration since its introduction into the market in the early 1990s. The goal of these reviews is to ensure that the herbicide carries out its intended use without creating adverse side effects to humans and the environment. Since scientific methods are continually evolving and being developed, global regulatory agencies can require additional studies to address data gaps for pesticide renewals. During this reregistration process for rimsulfuron, a new confined rotational crop study was required to address a data gap requested by the European Food Safety Authority (EFSA). Consequently, the corresponding pyridine and pyrimidine radiolabeled [14C]rimsulfuron and [M + 3] stable isotopes of rimsulfuron were synthesized for this study to support the reregistration process.\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 7","pages":"263-272"},"PeriodicalIF":0.9,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864983","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

Efficient Reductive N-11C-Methylation Using Arylamines or Alkylamines and In Situ–Generated [11C]Formaldehyde From [11C]Methyl Iodide 使用芳基胺或烷基胺进行高效的 N-11C 甲基化还原反应，以及由 [11C]Methyl Iodide 原位生成 [11C]Formaldehyde

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-05-04 DOI: 10.1002/jlcr.4095

Tatsuya Kikuchi, Toshimitsu Okamura, Ming-Rong Zhang

{"title":"Efficient Reductive N-11C-Methylation Using Arylamines or Alkylamines and In Situ–Generated [11C]Formaldehyde From [11C]Methyl Iodide","authors":"Tatsuya Kikuchi, Toshimitsu Okamura, Ming-Rong Zhang","doi":"10.1002/jlcr.4095","DOIUrl":"10.1002/jlcr.4095","url":null,"abstract":"<div>\u0000 \u0000 Reductive N-11C-methylation using [11C]formaldehyde and amines has been used to prepare N-11C-methylated compounds. However, the yields of the N-11C-methylated compounds are often insufficient. In this study, we developed an efficient method for base-free reductive N-11C-methylation that is applicable to a wide variety of substrates, including arylamines bearing electron-withdrawing and electron-donating substituents. A 2-picoline borane complex, which is a stable and mild reductant, was used. Dimethyl sulfoxide was used as the primary reaction solvent, and glacial acetic acid or aqueous acetic acid was used as a cosolvent. While reductive N-11C-methylation efficiently proceeded under anhydrous conditions in most cases, the addition of water to the reductive N-11C-methylation generally increased the yield of the N-11C-methylated compounds. Substrates with hydroxy, carboxyl, nitrile, nitro, ester, amide, and phenone moieties and amine salts were applicable to the reaction. This proposed method for reductive N-11C-methylation should be applicable to a wide variety of substrates, including thermo-labile and base-sensitive compounds because the reaction was performed under relatively mild conditions (70°C) without the need for a base.\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 7","pages":"254-262"},"PeriodicalIF":0.9,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829326","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

11C-Carbonylation for PET Imaging and Drug Discovery 用于 PET 成像和药物发现的 11C 碳酰化技术

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-05-01 DOI: 10.1002/jlcr.4094

Kenneth Dahl

引用次数: 0

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

IF 0.9 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 0.9 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":0.9,"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 0.9 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