Journal of labelled compounds & radiopharmaceuticals最新文献

{"title":"Improved protocol for the radiosynthesis of [18F]FTC-146: A potent and selective sigma-1 receptor radioligand","authors":"Masoud Sadeghzadeh,&nbsp;Barbara Wenzel,&nbsp;Julia Nikodemus,&nbsp;Alexandru Florea,&nbsp;Fabian Hertel,&nbsp;Klaus Kopka,&nbsp;Andreas T. J. Vogg,&nbsp;Fabian Kiessling,&nbsp;Felix M. Mottaghy","doi":"10.1002/jlcr.4018","DOIUrl":"https://doi.org/10.1002/jlcr.4018","url":null,"abstract":"<p>[¹⁸F]FTC-146 was introduced as a very potent and selective sigma-1 receptor radioligand, which has shown promising application as an imaging agent for neuropathic pain with positron emission tomography. In line with a multi-laboratory project on animal welfare, we chose this radioligand to investigate its potential for detecting neuropathic pain and tissue damage in tumor-bearing animals. However, the radiochemical yield (RCY) of around 4–7% was not satisfactory to us, and efforts were made to improve it. Herein, we describe an improved approach for the radiosynthesis of [¹⁸F]FTC-146 resulting in a RCY, which is sevenfold higher than that previously reported. A tosylate precursor was synthesized and radio-fluorination experiments were performed via aliphatic nucleophilic substitution reactions using either K[¹⁸F]F-Kryptofix®222 (K_2.2.2)-carbonate system or tetra-n-butylammonium [¹⁸F]fluoride ([¹⁸F]TBAF). Several parameters affecting the radiolabeling reaction such as solvent, ¹⁸F-fluorination agent with the corresponding amount of base, labeling time, and temperature were investigated. Best labeling reaction conditions were found to be [¹⁸F]TBAF and acetonitrile as solvent at 100°C. The new protocol was then translated to an automated procedure using a FX2 N synthesis module. Finally, the radiotracer reproducibly obtained with RCYs of 41.7 ± 4.4% in high radiochemical purity (&gt;98%) and molar activities up to 171 GBq/μmol.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 3","pages":"116-125"},"PeriodicalIF":1.8,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50138679","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":"Radioiodination, purification, and evaluation of antihuman tumor-derived immunoglobulin G light chain monoclonal antibody in tumor-bearing nude mice","authors":"Hongwei Sun,&nbsp;Ping Yan,&nbsp;Rongfu Wang,&nbsp;Yujing Du,&nbsp;Chunli Zhang,&nbsp;Fengqin Guo,&nbsp;Lei Kang,&nbsp;Yonggang Cui","doi":"10.1002/jlcr.4017","DOIUrl":"10.1002/jlcr.4017","url":null,"abstract":"<p>We report the synthesis and biological evaluation of ¹³¹I-labeled antihuman tumor-derived immunoglobulin G (IgG) light chain monoclonal antibody (4E9) ([¹³¹I]I-4E9) as a promising probe for tumor imaging. [¹³¹I]I-4E9 was synthesized in radiochemical yield of 89.9 ± 4.7% with radiochemical purity of more than 99%. [¹³¹I]I-4E9 showed high stability in normal saline and human serum. In cell uptake studies, [¹³¹I]I-4E9 exhibited favorable binding affinity and high specificity in HeLa MR cells. In biodistribution studies, [¹³¹I]I-4E9 showed high tumor uptake, high tumor/non-tumor ratios, and specific binding in BALB/c nu/nu mice bearing human HeLa MR xenografts. Single-photon emission computerized tomography (SPECT) imaging of [¹³¹I]I-4E9 in the HeLa MR xenograft model demonstrated clear visualization of tumor after 48 h and confirmed specific binding in tumor. These findings suggest that [¹³¹I]I-4E9 possesses favorable biological characteristics and warrants further investigation as a prospective probe for imaging and treatment of cancers.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 3","pages":"108-115"},"PeriodicalIF":1.8,"publicationDate":"2023-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9586132","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":"Evaluation and improvement of CuI-mediated 11C-cyanation","authors":"Hideki Ishii,&nbsp;Tomoteru Yamasaki,&nbsp;Toshimitsu Okamura,&nbsp;Yiding Zhang,&nbsp;Yusuke Kurihara,&nbsp;Masanao Ogawa,&nbsp;Nobuki Nengaki,&nbsp;Ming-Rong Zhang","doi":"10.1002/jlcr.4016","DOIUrl":"https://doi.org/10.1002/jlcr.4016","url":null,"abstract":"<p>CuI-mediated ¹¹C-cyanation was evaluated by synthesizing [¹¹C]perampanel ([¹¹C]<b>5</b>) as a model compound and compared with previous reports. To a DMF solution with 5′-(2-bromophenyl)-1′-phenyl-[2,3′-bipyridin]-6′(1′H)-one (<b>4</b>) and CuI, [¹¹C]NH₄CN in a stream of ammonia/nitrogen (5:95, v/v) gas was bubbled. Subsequently, the reaction mixture was heated at 180°C for 5 min. After HPLC purification, [¹¹C]<b>5</b> was obtained in 7.2 ± 1.0% (<i>n</i> = 4) non-decay corrected radiochemical yield with &gt;99% radiochemical purity and a molar activity of 98 ± 28 GBq/μmol. In vivo evaluations of [¹¹C]<b>5</b> were performed using small animals. PET scans to check the kinetics of [¹¹C]<b>5</b> in the whole body of mice suggested that [¹¹C]<b>5</b> spreads rapidly into the brain, heart, and lungs and then accumulates in the small intestine. To evaluate the performance of CuI-mediated ¹¹C-cyanation reaction, bromobenzene (<b>6a</b>) was selected as the model compound; however, it failed. Therefore, optimization of the reaction conditions has been performed, and consequently, the addition of K₂CO₃ and prolonging the reaction time improved the radiochemical yield about double. With this improved method, CuI-mediated ¹¹C-cyanation of various (hetero)aromatic bromides was performed to exhibit the tolerance of most functional groups and to provide ¹¹C-cyanated products in good to moderate radiochemical yields.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 3","pages":"95-107"},"PeriodicalIF":1.8,"publicationDate":"2023-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50133489","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":"Highly selective catalytic transfer hydrodeuteration of cyclic alkenes","authors":"Samuel J. Hintzsche,&nbsp;Zoua Pa Vang,&nbsp;Emanuel Rivera Torres,&nbsp;Mykaela Podoski,&nbsp;Joseph R. Clark","doi":"10.1002/jlcr.4015","DOIUrl":"10.1002/jlcr.4015","url":null,"abstract":"<p>Selective deuterium installation into small molecules is becoming increasingly desirable not only for the elucidation of mechanistic pathways and studying biological processes but also because of deuterium's ability to favorably adjust the pharmacokinetic parameters of bioactive molecules. Fused bicyclic moieties, especially those containing heteroatoms, are prevalent in drug discovery and pharmaceuticals. Herein, we report a copper-catalyzed transfer hydrodeuteration of cyclic and heterocyclic alkenes, which enables the synthesis of chromans, quinolinones, and tetrahydronaphthalenes that are precisely deuterated at the benzylic position. We also demonstrate the ability to place one deuterium atom at the homobenzylic site of these scaffolds with high regioselectivity by swapping transfer reagents for their isotopic analogs. Furthermore, examples of chemoselective transfer hydrogenation and transfer deuteration are disclosed, allowing for the simultaneous incorporation of two vicinal hydrogen or deuterium atoms into a double bond.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 3","pages":"86-94"},"PeriodicalIF":1.8,"publicationDate":"2023-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10226366/pdf/nihms-1899155.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9527623","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":"[18F]Fluoropyridine-losartan: A new approach toward human Positron Emission Tomography imaging of Angiotensin II Type 1 receptors","authors":"Aida Mary Abreu Diaz,&nbsp;Zalua Rodriguez Riera,&nbsp;Yanick Lee,&nbsp;Luis Miguel Esteves,&nbsp;Charles-Olivier Normandeau,&nbsp;Baptiste Fezas,&nbsp;Alejandro Hernandez Saiz,&nbsp;François Tournoux,&nbsp;Daniel Juneau,&nbsp;Jean N. DaSilva","doi":"10.1002/jlcr.4014","DOIUrl":"https://doi.org/10.1002/jlcr.4014","url":null,"abstract":"<p>Angiotensin II type 1 receptors (AT₁R) blocker losartan is used in patients with renal and cardiovascular diseases. [¹⁸F]fluoropyridine-losartan has shown favorable binding profile for quantitative renal PET imaging of AT₁R with selective binding in rats and pigs, low interference of radiometabolites and appropriate dosimetry for clinical translation. A new approach was developed to produce [¹⁸F]fluoropyridine-losartan in very high molar activity. Automated radiosynthesis was performed in a three-step, two-pot, and two-HPLC-purification procedure within 2 h. Pure [¹⁸F]FPyKYNE was obtained by radiofluorination of NO₂PyKYNE and silica-gel-HPLC purification (40 ± 9%), preventing the formation of nitropyridine-losartan in the second step. Conjugation with trityl-losartan azide via click chemistry, followed by acid hydrolysis, C18-HPLC purification and reformulation provided [¹⁸F]fluoropyridine-losartan in 11 ± 2% (decay-corrected from [¹⁸F]fluoride, EOB). Using tris[(1-(3-hydroxypropyl)-1<i>H</i>-1,2,3-triazol-4-yl)methyl]-amine (THPTA) as a Cu(I)-stabilizing agent for coupling [¹⁸F]FPyKYNE to the unprotected losartan azide afforded [¹⁸F]fluoropyridine-losartan in similar yields (11 ± 3%, decay-corrected from [¹⁸F]fluoride, EOB). Reverse-phase HPLC was optimized by reducing the pH of the mobile phase to achieve complete purification and high molar activities (467 ± 60 GBq/μmol). The use of radioprotectants prevented tracer radiolysis for 10 h (RCP &gt; 99%). The product passed the quality control testing. This reproducible automated radiosynthesis process will allow in vivo PET imaging of AT₁R expression in several diseases.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 3","pages":"73-85"},"PeriodicalIF":1.8,"publicationDate":"2023-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50152347","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":"Development of a high-performance liquid chromatography method for rapid radiochemical purity measurement of [18F]PSMA-1007, a PET radiopharmaceutical for detection of prostate cancer","authors":"Joseph A. Ioppolo,&nbsp;Eva Alvarez de Eulate,&nbsp;Danica R. Cullen,&nbsp;Shifaza Mohamed,&nbsp;Laurence Morandeau","doi":"10.1002/jlcr.4013","DOIUrl":"https://doi.org/10.1002/jlcr.4013","url":null,"abstract":"<p>Since first becoming commercially available in 2018, the PET radiopharmaceutical [¹⁸F]PSMA-1007 has been used widely for the diagnosis and staging of prostate cancer. A pharmacopoeia monograph first became available in 2021, prescribing a radiochemical purity specification of &gt;91%, based on analytical results from both TLC (for [¹⁸F]fluoride impurity alone) and HPLC (for all other ¹⁸F-impurities). Though this monograph has provided clarity for the quality control testing of [¹⁸F]PSMA-1007, it prescribes a HPLC method using phosphate buffer mobile phase that may present a risk of precipitation of phosphate salts in the HPLC system. The method also requires specialised hardware not immediately available to all laboratories. This work describes the development of a simple, rapid reversed-phase HPLC method utilising 0.1 M ammonium formate mobile phase for the accurate assessment of both [¹⁸F]fluoride impurity and overall radiochemical purity in a single test. This method is especially useful for assessment of product stability over time. A more accurate TLC method for [¹⁸F]fluoride impurity is also described.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 3","pages":"58-72"},"PeriodicalIF":1.8,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50135718","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":"An optimized radiosynthesis of [18F]DK222, a PET radiotracer for imaging PD-L1","authors":"Daniel P. Holt,&nbsp;Dhiraj Kumar,&nbsp;Sridhar Nimmagadda,&nbsp;Robert F. Dannals","doi":"10.1002/jlcr.4012","DOIUrl":"https://doi.org/10.1002/jlcr.4012","url":null,"abstract":"<p>A radiochemical synthesis of [¹⁸F]DK222, a peptide binder of programmed death ligand 1 protein, suitable for human PET studies is described, and results from validation productions are presented. The high specific activity radiotracer product is prepared as a sterile, apyrogenic solution that conforms to current Good Manufacturing Practice (cGMP) requirements. In addition, the production is extended to use a commercial synthesizer platform (General Electric FASTlab 2).</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 2","pages":"47-54"},"PeriodicalIF":1.8,"publicationDate":"2023-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50127319","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":"Detailed radiosynthesis of [18F]mG4P027 as a positron emission tomography radiotracer for mGluR4","authors":"Junfeng Wang,&nbsp;Sung-Hyun Moon,&nbsp;Michael B. Cleary,&nbsp;Timothy M. Shoup,&nbsp;Georges El Fakhri,&nbsp;Zhaoda Zhang,&nbsp;Anna-Liisa Brownell","doi":"10.1002/jlcr.4011","DOIUrl":"https://doi.org/10.1002/jlcr.4011","url":null,"abstract":"<p>We report here the detailed radiosynthesis of [¹⁸F]<b>mG4P027</b>, a metabotropic glutamate receptor 4 (mGluR4) PET radiotracer, which showed superior properties to the currently reported mGluR4 radiotracers. The radiosynthesis in the automated system has been challenging, therefore we disclose here the major limiting factors for the synthesis via step-by-step examination. And we hope this thorough study will help its automation for human use in the future.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 2","pages":"34-40"},"PeriodicalIF":1.8,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50118241","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 analysis of isotopically stable labeled nitrosamines as mass spectrometry standards for drug impurity quality control","authors":"Volker Derdau,&nbsp;Martin Sandvoss","doi":"10.1002/jlcr.4010","DOIUrl":"10.1002/jlcr.4010","url":null,"abstract":"We describe a simple and easy pathway to synthesize nitrosamine mass spectrometry standards in good to moderate yields. N-alkylation of Boc-protected primary or secondary amines using stable isotope labeled alkyl halides yielded the key intermediates that were deprotected, and then, the nitrosamine was formed with sodium nitrite and sodium hydrogensulfate. Special attention to safety, disposal of waste, and surface cleaning was carried throughout.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 2","pages":"41-46"},"PeriodicalIF":1.8,"publicationDate":"2022-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10834890","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 radiolabeling of a polar [125I]I-1,2,4,5-tetrazine","authors":"Natasha Bidesi,&nbsp;Vladimir Shalgunov,&nbsp;Umberto Maria Battisti,&nbsp;Lars Hvass,&nbsp;Jesper Tranekjær Jørgensen,&nbsp;Christian B. M. Poulie,&nbsp;Andreas I. Jensen,&nbsp;Andreas Kjaer,&nbsp;Matthias M. Herth","doi":"10.1002/jlcr.4009","DOIUrl":"https://doi.org/10.1002/jlcr.4009","url":null,"abstract":"<p>Pretargeting imaging has gained a lot of prominence, due to its excellent bioorthogonality and improved imaging contrast compared to conventional imaging. A new iodo tetrazine (Tz) derivative has been synthesized and further developed into the corresponding iodine-125 (¹²⁵I) analog (<b>12</b>), via the trimethylstannane precursor. Radiolabeling with either <i>N</i>-chlorosuccinimide or chloramine-T, in either MeCN or MeOH proceeded with a radiochemical conversion (RCC) of &gt;80%. Subsequent deprotection only proved successful, among the tested conditions, when the radiolabeled Tz was stirred in 6-M HCl_(aq.) at 60°C for 2.5 h. To the best of our knowledge, this is the first H-tetrazine labeled with iodine. In vivo investigations on the pretargeting ability of <b>12</b> are currently under way.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 1","pages":"22-30"},"PeriodicalIF":1.8,"publicationDate":"2022-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50138324","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}