Journal of labelled compounds & radiopharmaceuticals最新文献

{"title":"Abstracts From the 29th International Isotope Society UK Meeting 17th November 2023","authors":"","doi":"10.1002/jlcr.4115","DOIUrl":"10.1002/jlcr.4115","url":null,"abstract":"<p>Matthew J. Fuchter<sup>1</sup></p><p>Department of Chemistry Imperial College London</p><p>Photoswitchable compounds, which can be reversibly switched between two isomers by light, continue to attract significant attention for a wide array of applications, from molecular motors, memory, and manipulators to solar thermal storage. Azoheteroarenes represent a relatively new but understudied type of photoswitch, where one or both of the aryl rings from the conventional azobenzene class has been replaced with a heteroaromatic ring. This talk will give an overview of our work in this area, initially focusing on our discovery of the arylazopyrazoles [1], which offer quantitative photoswitching and high thermal stability of the <i>Z</i> isomer. It will go on to describe our elucidation of structure–property relationships for a wide array of comparable azoheteroaryl photoswitches [2, 3]. Through this, we have identified compounds with <i>Z</i> isomer half-lives ranging from seconds to hours, to days and to years, and variable absorption characteristics, all through tuning of the heteraromatic ring.</p><p>Given the large tunability of their properties, the predictive nature of their performance, and the other potential functional opportunities afforded by usage of a heteroaromatic system, we believe the azoheteroaryl photoswitches to have huge potential in a wide range of optically addressable applications. This talk will particularly focus on the promise of such agents in photopharmacology: light-addressable drugs [4–6].</p><p><b>References</b></p><p>1. \u0000 <span>C. E. Weston</span>, <span>R. D. Richardson</span>, <span>P. R. Haycock</span>, <span>A. J. P. White</span>, and <span>M. J. Fuchter</span>, “ <span>Arylazopyrazoles: Azoheteroarene Photoswitches Offering Quantitative Isomerization and Long Thermal Half-Lives</span>,”<i>Journal of the American Chemical Society</i> <span>136</span>, (<span>2014</span>): <span>11878</span>–<span>11881</span>.</p><p>2. \u0000 <span>J. Calbo</span>, <span>C. E. Weston</span>, <span>A. J. P. White</span>, <span>H. Rzepa</span>, <span>J. Contreras-García</span>, and <span>M. J. Fuchter</span>, “ <span>Tuning Azoheteroarene Photoswitch Performance Through Heteroaryl Design</span>,” <i>Journal of the American Chemical Society</i> <span>139</span>, (<span>2017</span>): <span>1261</span>–<span>1274</span>.</p><p>3. \u0000 <span>A. Gonzalez</span>, <span>M. Odaybat</span>, <span>M. Le</span>, et al., “ <span>Photocontrolled Energy Storage in Azobispyrazoles With Exceptionally Large Light Penetration Depths</span>,” <i>Journal of the American Chemical Society</i> <span>144</span>, (<span>2022</span>): <span>19430</span>–<span>19436</span>.</p><p>4. \u0000 <span>C. E. Weston</span>, <span>A. Kraemer</span>, <span>F. Colin</span>, et al., “ <span>Toward Photopharmacological Antimicrobial Chemotherapy Using Photoswitchable Amidohydrolase Inhibitors</span>,” <i>ACS Infectious Diseases</i> <span>3</span>, (<span>2017</span>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 10","pages":"349-356"},"PeriodicalIF":0.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008907","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}

{"title":"Lead-212/Bismuth-212 In Vivo Generator Based on Ultrasmall Silver Telluride Nanoparticles","authors":"Runze Wang,&nbsp;Hubert Th. Wolterbeek,&nbsp;Antonia G. Denkova","doi":"10.1002/jlcr.4121","DOIUrl":"10.1002/jlcr.4121","url":null,"abstract":"<p>Radionuclide therapy employing alpha emitters holds great potential for personalized cancer treatment. However, certain challenges remain when designing alpha radiopharmaceuticals, including the lack of stability of used radioconjugates due to nuclear decay events. In this work, ultrasmall silver telluride nanoparticles with a core diameter of 2.1 nm were prepared and radiolabeled with lead-212 using a chelator-free method with a radiolabeling efficiency of 75%. The results from the in vitro radiochemical stability assay indicated a very high retention of bismuth-212 despite the internal conversion effects originating from the decay of ²¹²Pb. To further evaluate the potential of the nanoparticles, they were radiolabeled with indium-111, and their cell uptake and subcellular distribution were determined in 2D U87 cells, showing accumulation in the nucleus. Although not intentional, it was observed that the indium-111-radiolabeled nanoparticles induced efficient tumor cell killing, which was attributed to the Auger electrons emitted by indium-111. Combining the results obtained in this work with other favorable properties such as fast renal clearance and the possibility to attach targeting vectors on the surface of the nanoparticles, all well-known from the literature, these ultra-small silver telluride nanoparticles provide exciting opportunities for the design of theragnostic radiopharmaceuticals.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 11","pages":"375-383"},"PeriodicalIF":0.9,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988122","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}

{"title":"68Ga Radiolabeling of NODASA-Functionalized Phage Display–Derived Peptides for Prospective Assessment as Tuberculosis-Specific PET Radiotracers","authors":"Christiaan A. Gouws,&nbsp;Tricia Naicker,&nbsp;Beatriz G. de la Torre,&nbsp;Fernando Albericio,&nbsp;Janie Duvenhage,&nbsp;Hendrik G. Kruger,&nbsp;Biljana Marjanovic-Painter,&nbsp;Sipho Mdanda,&nbsp;Jan R. Zeevaart,&nbsp;Thomas Ebenhan,&nbsp;Thavendran Govender","doi":"10.1002/jlcr.4120","DOIUrl":"10.1002/jlcr.4120","url":null,"abstract":"<p>This research presents the development of positron emission tomography (PET) radiotracers for detecting <i>Mycobacterium tuberculosis</i> (MTB) for the diagnosis and monitoring of tuberculosis. Two phage display–derived peptides with proven selective binding to MTB were identified for development into PET radiopharmaceuticals: H8 (linear peptide) and PH1 (cyclic peptide). We sought to functionalize H8/PH1 with NODASA, a bifunctional chelator that allows complexation of PET-compatible radiometals such as gallium-68. Herein, we report on the chelator functionalization, optimized radiosynthesis, and assessment of the radiopharmaceutical properties of [⁶⁸Ga]Ga-NODASA-H8 and [⁶⁸Ga]Ga-NODASA-PH1. Robust radiolabeling was achieved using the established routine method, indicating consistent production of a radiochemically pure product (RCP ≥ 99.6%). For respective [⁶⁸Ga]Ga-NODASA-H8 and [⁶⁸Ga]Ga-NODASA-PH1, relatively high levels of decay-corrected radiochemical yield (91.2% ± 2.3%, 86.7% ± 4.0%) and apparent molar activity (<i>A</i>_m, 3.9 ± 0.8 and 34.0 ± 5.3 GBq/μmol) were reliably achieved within 42 min, suitable for imaging purposes. Notably, [⁶⁸Ga]Ga-NODASA-PH1 remained stable in blood plasma for up to 2 h, while [⁶⁸Ga]Ga-NODASA-H8 degraded within 30 min. For both ⁶⁸Ga peptides, minimal whole-blood cell binding and plasma protein binding were observed, indicating a favorable pharmaceutical behavior. [⁶⁸Ga]Ga-NODASA-PH1 is a promising candidate for further in vitro/in vivo evaluation as a tuberculosis-specific infection imaging agent.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 11","pages":"360-374"},"PeriodicalIF":0.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906806","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}

{"title":"Application of Microfluidic Devices for Automated Two-Step Radiolabeling of Antibodies","authors":"Hiroki Jinda,&nbsp;Hiroyuki Watanabe,&nbsp;Kazuma Nakashima,&nbsp;Masahiro Ono","doi":"10.1002/jlcr.4119","DOIUrl":"10.1002/jlcr.4119","url":null,"abstract":"<div>\u0000 \u0000 <p>Radioimmunoconjugates (RICs) composed of tumor-targeting monoclonal antibodies and radionuclides have been developed for diagnostic and therapeutic application. A new radiolabeling method using microfluidic devices is expected to facilitate simpler and more rapid synthesis of RICs. In the microfluidic method, microfluidic chips can promote the reaction between reactants by mixing them efficiently, and pumping systems enable automated synthesis. In this study, we synthesized RICs by the pre-labeling method, in which the radiometal is coordinated to the chelator and then the radiolabeled chelator is incorporated into the antibodies, using microfluidic devices for the first time. As a result of examining the reaction parameters including the material of mixing units, reaction temperature, and flow rate, RICs with radiochemical purity (RCP) exceeding 90% were obtained. These high-purity RICs were successfully synthesized without any purification simply by pumping three solutions of a chelating agent, radiometal, and antibody into microfluidic devices. Under the same conditions, the RCP of RICs labeled by conventional methods was below 50%. These findings indicate the utility of microfluidic devices for automatic and rapid synthesis of high-quality RICs.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 10","pages":"341-348"},"PeriodicalIF":0.9,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897627","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}

{"title":"Synthesis and Preclinical Evaluation of [18F]AlF-NOTA-Asp2-PEG2-Folate as a Novel Folate-Receptor-Targeted Tracer for PET Imaging","authors":"Haoran Liang,&nbsp;Zihao Chen,&nbsp;Chunwei Mo,&nbsp;Ganghua Tang","doi":"10.1002/jlcr.4118","DOIUrl":"10.1002/jlcr.4118","url":null,"abstract":"<div>\u0000 \u0000 <p>Recently, the folate receptor (FR) has become an exciting target for the diagnosis of FR-positive malignancies. Nevertheless, suboptimal in vivo pharmacokinetic properties, particularly high uptake in the renal and hepatobiliary systems, are important limiting factors for the clinical translation of most FR-based radiotracers. In this study, we developed a novel ¹⁸F-labeled FR-targeted positron emission tomography (PET) tracer [¹⁸F]AlF-NOTA-Asp₂-PEG₂-Folate modified with a hydrophilic linker (−Asp₂-PEG₂) to optimize its pharmacokinetic properties and conducted a comprehensive preclinical assessment. The [¹⁸F]AlF-NOTA-Asp₂-PEG₂-Folate was manually synthesized within 30 min with a non-decay-corrected radiochemical yield of 16.3 ± 2.0% (<i>n</i> = 5). Among KB cells, [¹⁸F]AlF-NOTA-Asp₂-PEG₂-Folate exhibited high specificity and affinity for FR. PET/CT imaging and biodistribution experiments in KB tumor-bearing mice showed decent tumor uptake (1.7 ± 0.3% ID/g) and significantly decreased uptake in kidneys and liver (22.2 ± 2.1 and 0.3 ± 0.1% ID/g at 60 min p.i., respectively) of [¹⁸F]AlF-NOTA-Asp₂-PEG₂-Folate, compared to the known tracer [¹⁸F]AlF-NOTA-Folate (78.6 ± 5.1 and 5.3 ± 0.5 % ID/g at 90 min p.i., respectively). The favorable properties of [¹⁸F]AlF-NOTA-Asp₂-PEG₂-Folate, including its efficient synthesis, decent tumor uptake, relatively low renal uptake, and rapid clearance from most normal organs, portray it as a promising PET tracer for FR-positive tumors.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 10","pages":"334-340"},"PeriodicalIF":0.9,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748358","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}

{"title":"Direct Multi-Deuterium Labelling of Pirtobrutinib","authors":"Michal Kriegelstein,&nbsp;Jana Hojcsková,&nbsp;Miloš Hroch,&nbsp;Aleš Marek","doi":"10.1002/jlcr.4117","DOIUrl":"10.1002/jlcr.4117","url":null,"abstract":"<div>\u0000 \u0000 <p>Herein, we demonstrate an efficient method for multi-deuterium labelling of pirtobrutinib—a Bruton's tyrosine kinase inhibitor recently approved by the FDA—using a straightforward hydrogen isotope exchange (HIE) reaction. A remarkably high level of deuterium incorporation was achieved using an excess of a Kerr-type iridium catalyst. The key factor in the significant deuterium labelling was the decision to employ a deuterium uniformly labelled solvent, chlorobenzene-<i>d</i>₅, at an elevated temperature. Virtually, no <i>d</i>₀–<i>d</i>₃ species were detected, with only traces of <i>d</i>₄–<i>d</i>₅ isotopomers (&lt; 5%) observable in the mass spectrum of pirtobrutinib-<i>d</i>₈, fulfilling requirements for stable isotope-labelled internal standard. The labelled compound—mainly consisting of isotopomers <i>d</i>₆–<i>d</i>₉ at 82.4% of the total abundance—was isolated in a high yield (73%) and purity (99%). Noteworthy, fluorine group acting as a directing group was observed for the first time. Significant incorporation of deuterium in <i>ortho</i>-positions, exceeding 87%, was observed. Interestingly, chlorinated solvent used in the HIE reactions was non-specifically deuterated yielding up to 0.42 deuterium per chlorobenzene molecule even at an exceptionally low iridium catalyst loading of 4.17 × 10^–2 mol%.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 9","pages":"314-323"},"PeriodicalIF":0.9,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616680","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}

{"title":"Fully Automated Cassette-Based Synthesis of 2-Deoxy-2-[18F]Fluorocellobiose Using Trasis AllInOne Module","authors":"Falguni Basuli,&nbsp;Jianfeng Shi,&nbsp;Swati Shah,&nbsp;Jianhao Lai,&nbsp;Dima A. Hammoud,&nbsp;Rolf E. Swenson","doi":"10.1002/jlcr.4116","DOIUrl":"10.1002/jlcr.4116","url":null,"abstract":"<div>\u0000 \u0000 <p>Due to the continuous rise in global incidence and severity of invasive fungal infections (IFIs), particularly among immunocompromised and immunodeficient patients, there is an urgent demand for swift and accurate fungal pathogen diagnosis. Therefore, the need for fungal-specific positron emission tomography (PET) imaging agents that can detect the infection in the early stages is increasing. Cellobiose, a disaccharide, is readily metabolized by fungal pathogens such as <i>Aspergillus</i> species. Recently, our group reported fluorine-18 labeled cellobiose, 2-deoxy-2-[¹⁸F]fluorocellobiose ([¹⁸F]FCB), for specific imaging of <i>Aspergillus</i> infection. The positive imaging findings with very low background signal on delayed imaging make this ligand a promising fungal-specific imaging ligand. Inspired by this result, the decision was made to automate the radiolabeling procedure for better reproducibility and to facilitate clinical translation. A Trasis AllInOne (Trasis AIO) automated module was used for this purpose. The reagent vials contain commercially available 2-deoxy-2-[¹⁸F]fluoroglucose ([¹⁸F]FDG), glucose-1-phosphate, and enzyme (cellobiose phosphorylase). A Sep-Pak cartridge was used to purify the tracer. The overall radiochemical yield was 50%–70% (<i>n</i> = 6, decay corrected) in 75-min synthesis time with a radiochemical purity of &gt; 98%. This is a highly reliable protocol to produce current good manufacturing practice (cGMP)–compliant [¹⁸F]FCB for clinical PET imaging.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 9","pages":"308-313"},"PeriodicalIF":0.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563548","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}

{"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,&nbsp;Mami Horikawa,&nbsp;Bradford D. Henderson,&nbsp;Allen F. Brooks,&nbsp;Peter J. H. Scott,&nbsp;Xia Shao","doi":"10.1002/jlcr.4113","DOIUrl":"10.1002/jlcr.4113","url":null,"abstract":"<p>A new automated radiosynthesis of [¹¹C]2-(2,6-difluoro-4-((2-(<i>N</i>-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 (<i>n</i> = 3). Batches passed all requisite quality control testing confirming suitability for clinical use.</p>","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}

{"title":"Synthesis and Evaluation of a Cathepsin B–Recognizing Trifunctional Chelating Agent to Improve Tumor Retention of Radioimmunoconjugates","authors":"Hiroki Jinda,&nbsp;Kazuma Nakashima,&nbsp;Hiroyuki Watanabe,&nbsp;Masahiro Ono","doi":"10.1002/jlcr.4112","DOIUrl":"10.1002/jlcr.4112","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\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}

{"title":"Carbon-14 Labeling Synthesis of RORγt Inhibitor JNJ-61803534","authors":"Fengbin Song,&nbsp;Rhys Salter,&nbsp;Lu Chen","doi":"10.1002/jlcr.4114","DOIUrl":"10.1002/jlcr.4114","url":null,"abstract":"<div>\u0000 \u0000 <p>Carbon-14 labeling synthesis of RORγt inhibitor JNJ-61803534 (<b>1</b>) was accomplished in four steps with the C14 label located at the thiazole-2-carboxamide carbon. The synthesis featured a highly efficient conversion of nitrile [¹⁴C]-<b>12</b> to ester [¹⁴C]-<b>17</b> under mild conditions via an imidate intermediate, overcoming the unsuccessful direct hydrolysis of nitrile <b>12</b> under either acidic or basic conditions. Since carbon-14 labeling via [¹⁴C]-nitrile installation and subsequent conversion to [¹⁴C]-carboxylic acid derivatives is a common labeling strategy, an efficient conversion of a nitrile to an ester under mild conditions could be of use for the future C14 labeling syntheses.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"67 8","pages":"288-294"},"PeriodicalIF":0.9,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158355","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}