Journal of labelled compounds & radiopharmaceuticals最新文献

{"title":"Synthesis of a Potent Bruton's Tyrosine Kinase Inhibitor Labelled With Carbon-14 and Deuterium","authors":"Bachir Latli,&nbsp;Magnus Eriksson","doi":"10.1002/jlcr.4148","DOIUrl":"https://doi.org/10.1002/jlcr.4148","url":null,"abstract":"<div>\u0000 \u0000 <p>Bruton's tyrosine kinase (BTK) is a cytoplasmic enzyme that plays a crucial role in B cell development, survival, proliferation and differentiation. This enzyme is expressed in several autoimmune diseases and cancers. Therefore, shutting out this enzyme with irreversible inhibitors is one of the strategies used to treat these diseases. The drug candidate <b>1</b> is a very potent and selective BTK inhibitor. Herein, we describe the preparation of this compound labelled with deuterium and carbon-14. Deuterium labelled <b>1</b> was prepared in 10 chemical steps and in 35% overall yield with more than 98% chemical purity and more than 99% isotopic enrichment. This synthesis was followed with the radioactive one as both synthetic routes were similar. Carbon-14 labelled <b>1</b> was prepared in eight radiochemical steps in 26% overall yield and in more than 99% radio and chemical purities and with specific activity of 53.1 mCi/mmol (1.96 GBq/mmol). This isotopically labelled compound was needed for DMPK and other studies.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 5-6","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909297","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":"Ultrasound-Assisted Microcontinuous Process Facilitates the Selective Deuteration of Steroid Hormones","authors":"Dan Wang,&nbsp;Xin Lv,&nbsp;Fang Wei","doi":"10.1002/jlcr.4146","DOIUrl":"https://doi.org/10.1002/jlcr.4146","url":null,"abstract":"<p>Constructing deuterated molecules efficiently and practically has been a long-standing challenge. Deuterated steroid hormones are essential for medical research and drug metabolism studies and are thus in high demand; mild and selective methods for the deuteration of steroid hormones have remained unexplored. Herein, we demonstrate a practical and efficient approach to synthesize 12 deuterated steroid hormones with up to 98% selectivity and 99% <i>d</i>-incorporation under an ultrasound-assisted microcontinuous process. Optical rotation experiments confirm that steroid hormones configurations are preserved during the H/D exchange reaction. Our protocol enables rapid, inexpensive, and sustainable gram-scale synthesis, facilitated by the reuse of deuterated solvents via molecular distillation technology. Applying synthetic deuterated steroid hormones as mass spectrometry standards, six steroid hormones in metabolites are accurately analyzed from Frozen Human Plasma-1950 sample. Overall, this work has successfully demonstrated the application of ultrasound assisted microcontinuous processing in enhancing H/D exchange reactions.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 5-6","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909371","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 of 18F-Labeled FC-119S and Its Tosyl Precursor","authors":"Koichi Kato,&nbsp;Makoto Funasaka,&nbsp;Jun Ogura,&nbsp;Eiko N. Minakawa,&nbsp;Kazuhiko Seki,&nbsp;Takuya Kumamoto","doi":"10.1002/jlcr.4145","DOIUrl":"https://doi.org/10.1002/jlcr.4145","url":null,"abstract":"<div>\u0000 \u0000 <p>Animal models of Alzheimer's disease (<span>AD</span>) are essential for developing therapeutics and evaluating the efficacy of new drug candidates. Positron emission tomography (PET) is a useful method to monitor a major hallmark of the onset of <span>AD</span>, namely, the deposition of amyloid β peptide (Aβ) in the brain. [¹⁸F]FC-119S (<b>1</b>), a 2-pyridylbenzothiazole analog, has been applied as a radiotracer for PET visualization of Aβ plaques in an <span>AD</span> model, the 5xFAD mouse. Here, we present an alternative method for the automated synthesis of ¹⁸F-labeled <b>1</b> as a radiotracer for our animal PET studies. The first attempt at synthesizing ¹⁸F-labeled <b>1</b> using a mesyl precursor afforded desired product <b>1</b>, although a nonfluorinated mesyl byproduct was eluted prior to <b>1</b> during purification by semipreparative high-performance liquid chromatography. An alternative synthesis using a tosyl precursor was applied to delay the elution of a nonfluorinated byproduct during chromatographic purification. As a result, ¹⁸F-labeled <b>1</b> was eluted without proximate byproducts during chromatographic purification, and routine production of ¹⁸F-labeled <b>1</b> was achieved for our <span>AD</span> studies using animal models.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 5-6","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909373","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":"Applications of Isotopes in Forensic Science","authors":"Crist N. Filer","doi":"10.1002/jlcr.4141","DOIUrl":"https://doi.org/10.1002/jlcr.4141","url":null,"abstract":"<div>\u0000 \u0000 <p>The existence of isotopes was proposed at the dawn of the 20^th century based on compelling experimental evidence by many distinguished investigators. The subject of this review focuses on one specific application of isotopes in the evolving science of forensics. The topics covered include isotope ratio measurement and variation, forensic anthropology, wildlife trafficking, explosive investigation, illicit drugs, counterfeit medicines, food authentication, nuclear forensics and artificial intelligence (AI). Future directions and a conclusion for this important research topic are also included.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 4","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717248","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 Peptide Dimer-Based PET Tracers for Imaging VEGFR-2 Expression in Tumors","authors":"He Wenjun,&nbsp;Chen Xueyao,&nbsp;Cai Qijun,&nbsp;Li Yingxin,&nbsp;Ran Bingyu,&nbsp;Cao Xiaoling,&nbsp;Cheng Yong,&nbsp;Jiang Yuanfang,&nbsp;Hou Lu,&nbsp;Ma Jie,&nbsp;Ye Weijian,&nbsp;Zhang Siqi,&nbsp;Wang Lu,&nbsp;Xu Hao,&nbsp;Hu Kuan,&nbsp;Shang Jingjie","doi":"10.1002/jlcr.4138","DOIUrl":"10.1002/jlcr.4138","url":null,"abstract":"<div>\u0000 \u0000 <p>The vascular endothelial growth factor A (VEGF-A)/VEGF receptor 2 (VEGFR-2) signaling pathway is pivotal in regulating angiogenesis. We have synthesized a linear peptide-based VEGFR-2–targeted positron emission tomography (PET) tracer, but its target affinity and in vivo stability need further improvement. In this study, we developed two novel ⁶⁴Cu-labeled VEGFR-2–targeted PET dimer tracer [⁶⁴Cu]VEGF₂₂₁₅ and [⁶⁴Cu]VEGF₂₂₁₆ modified with a pegylated linear and branched linker, respectively, to optimize its pharmacokinetic properties and conducted a comprehensive preclinical assessment. Both tracers exhibited a radiochemical yield of over 95% and showed a high affinity for VEGFR-2 in U87MG cells. PET/CT imaging experiments indicated that [⁶⁴Cu]VEGF₂₂₁₅ exhibited a time-dependent accumulation in the U87MG tumor, with a maximum uptake of 4.95 ± 1.26 %ID/g at 24 h post-injection. In comparison, [⁶⁴Cu]VEGF₂₂₁₆ showed a consistently lower tumor uptake, peaking at only 3.07 ± 0.35 %ID/g. Blocking and biodistribution experiments further confirmed the specificity of [⁶⁴Cu]VEGF₂₂₁₅ for VEGFR-2. The favorable properties of [⁶⁴Cu]VEGF₂₂₁₅, including efficient synthesis, high tumor uptake, and rapid clearance from most normal organs, suggest it is a promising PET tracer for VEGFR-2-positive tumors.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 3","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670120","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":"A Novel 68Ga-Labeled 2-Azabicyclo[3.1.0]Hexane-3-Carbonitrile-Based Fibroblast Activation Protein-Targeted Tracer for Cancer Imaging With Positron Emission Tomography","authors":"Chao-Cheng Chen,&nbsp;Lei Wang,&nbsp;Antonio A. W. L. Wong,&nbsp;Wing Sum Lau,&nbsp;Pauline Ng,&nbsp;Helen Merkens,&nbsp;François Bénard,&nbsp;Kuo-Shyan Lin","doi":"10.1002/jlcr.4143","DOIUrl":"https://doi.org/10.1002/jlcr.4143","url":null,"abstract":"<div>\u0000 \u0000 <p>Most of the reported small molecule-based fibroblast activation protein (FAP)-targeted radioligands are derived from UAMC1110 and contain a 4-difluoro-2-cyanopyrrolidine moiety. In this study, we investigated the effect of replacing the 4-difluoro-2-cyanopyrrolidine moiety of [⁶⁸Ga]Ga-FAPI-04 with 2-azabicyclo[3.1.0]hexane-3-carbonitrile on the in vitro<i>/vivo</i> FAP-targeting capability. The newly derived ⁶⁸Ga-labeled FAP-targeted tracer, [⁶⁸Ga]Ga-JC02076, was obtained in 43.5 ± 10.4% decay-corrected radiochemical yield within 33.5 ± 5.8 min (<i>n</i> = 4). The radiochemical purity and molar activity were 97.2 ± 3.4% and 411.6 ± 232.5 GBq/μmol, respectively. Ga-JC02076 showed good binding affinity for FAP (IC₅₀ = 29.7 ± 3.5 nM). Most importantly, [⁶⁸Ga]Ga-JC02076 enabled clear visualization of HEK293T:hFAP tumor xenografts in PET images and had good tumor uptake (7.17 ± 2.19 %ID/g) and excellent tumor-to-bone (17.3 ± 6.99) and tumor-to-muscle (32.3 ± 12.5) uptake ratios at 1 h post-injection. Our data suggest that <i>N</i>-(4-quinolinoyl)-Gly-(2-azabicyclo[3.1.0]hexane-3-carbonitrile) is a promising pharmacophore for the design of FAP-targeted tracers.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 3","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632832","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":"Preparation of Macrobicyclic Cryptands for Radiometal Complexation","authors":"Laura Höffmann,&nbsp;Magdalena Blei,&nbsp;Falco Reissig,&nbsp;Klaus Kopka,&nbsp;Constantin Mamat","doi":"10.1002/jlcr.4136","DOIUrl":"https://doi.org/10.1002/jlcr.4136","url":null,"abstract":"<p>Macrobicyclic cryptands and especially derivatives with functionalized side arms (picolinate, pyrimidine carboxylate, and bipyridine carboxylate) are able to complex metal ions effectively. In this regard, four new functionalized cryptands were prepared in a convenient two-step synthesis procedure starting from basic compound 4,10,16,22,27-pentaoxa-1,7,13,19-tetraazabicyclo[11.11.5]nonacosane and fully characterized. Their complexation behavior was tested via ¹H NMR titration with Ba²⁺, Sc³⁺, La³⁺, Lu³⁺, In³⁺, and Pb²⁺ pointing out log <i>K</i> values between 1.4 and 4.0. Radiolabeling with selected cations of radiopharmaceutical relevance (¹³¹Ba, ²²⁵Ac, and ¹³³La) was performed.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 3","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554384","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":"Design and Synthesis of a 18F-Radiolabeled Pyrrolo[2,3-d]pyrimidine Ligand as a CSF1R Receptor PET Imaging Agent","authors":"Srinivasulu Cherukupalli,&nbsp;Morten Karlsen,&nbsp;Bård Helge Hoff,&nbsp;Eirik Sundby","doi":"10.1002/jlcr.4131","DOIUrl":"https://doi.org/10.1002/jlcr.4131","url":null,"abstract":"<div>\u0000 \u0000 <p>Colony-stimulating factor 1 receptor (CSF1R or c-FMS), a class III receptor tyrosine kinase, is significantly expressed in mononuclear phagocytes and in the central nervous system. It has been identified as a potential drug and imaging target in numerous inflammatory, cancerous, and neurodegenerative diseases. Despite several attempts, no validated CSF1R PET tracer is currently available. Herein, we report the design and synthesis of a ¹⁸F-radiolabeled pyrrolo[2,3-<i>d</i>]pyrimidine molecule based on previously developed potent and selective CSF1R inhibitors. Initially, a nonlabeled fluorinated compound was synthesized using conventional and microwave methods, and it exhibited potent CSF1R inhibitory activity (IC₅₀ = 6 nM). A tosylate precursor was then synthesized for subsequent radiofluorination. The ¹⁸F-radiolabeled compound was produced using K[¹⁸F]F Kryptofix 222 (K_2.2.2)-carbonate in acetonitrile (10% DMF). The optimal labeling conditions, with a tosylate leaving group at 100°C for 5 min, resulted in the production of the ¹⁸F-radiolabeled pyrrolo[2,3-<i>d</i>]pyrimidine CSF1R inhibitor with high purity and with a molar activity of the final product of 57 GBq/μmol. The synthesized inhibitor might open new possibilities for in vivo imaging in neuroinflammation and related disorders, and future studies will evaluate its performance as a PET tracer.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 1-2","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481520","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":"Evaluation of New-Modelled Recombinant Human Insulin (rh-Insulin) Analog Expressed in E. coli Using Radioiodination Technique Followed by In Vivo Biodistribution in Diabetes-Induced Mice","authors":"Gamal Abdelaziz,&nbsp;Ibrahim Y. Abdelghany,&nbsp;Nasser F. Mostafa","doi":"10.1002/jlcr.4134","DOIUrl":"https://doi.org/10.1002/jlcr.4134","url":null,"abstract":"<div>\u0000 \u0000 <p>Biologists have significantly improved various techniques for confirming the physiological and pharmacological activity of new proteins produced by recombinant DNA technology, such as Western blotting, ELISA, and flow cytometry. Although these methods are costly and comparatively low in efficiency, our study focuses on developing a real-time approach to investigate the physiological activity of our new recombinant human insulin (rh-Insulin), which is expressed in <i>Escherichia coli</i>. An in vivo biodistribution study of radioiodinated rh-Insulin (¹²⁵I-rh-Insulin) was conducted in diabetic-induced mice, exploiting the capability of tyrosine residues in protein molecules to undergo electrophilic substitution of hydrogen atoms with traceable ¹²⁵I atoms. We studied many factors to optimize the conditions for the iodination reaction, including the amount of substrate, the amount of chloramine-T, pH, temperature, and reaction time. A high radiochemical yield of 99.01 ± 0.2% was achieved. The in vivo step involved the administration of ¹²⁵I-rh-Insulin intravenously (I.V.) in previously induced diabetic mice to study the pharmacokinetics of the new insulin analog. Results show a homogeneous distribution of insulin molecules throughout the body organs, correlating with organ mass, size, and functionality, with no accumulation in distinct organs. The clearance of insulin from the body occurs via both renal and hepatic routes due to the aqueous nature of insulin. Additionally, a parallel experiment was conducted on diabetic mice using only rh-Insulin, resulting in a significant reduction in glucose levels in the mice's blood, thereby exploring the physiological activity of insulin and confirming the ability of our new construct to lower blood glucose levels in diabetic mice. Consequently, this method appears to be much more rapid and effective for the evaluation of biological molecules in vivo using radioactive tracing techniques.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 1-2","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481568","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":"Current Advances in PARP1-Targeted Theranostics","authors":"Jie Tong,&nbsp;Baosheng Chen,&nbsp;Tommaso Volpi,&nbsp;Yawen Li,&nbsp;Paul A. Ellison,&nbsp;Zhengxin Cai","doi":"10.1002/jlcr.4135","DOIUrl":"https://doi.org/10.1002/jlcr.4135","url":null,"abstract":"<div>\u0000 \u0000 <p>Poly (ADP-ribose) polymerase 1 (PARP1) plays critical roles in DNA repair, chromatin regulation, and cellular equilibrium, positioning it as a pivotal target for therapeutic interventions in cancer and central nervous system (CNS) disorders. PARP1 responds to oxidative stress and DNA damage through PARylation, influencing energy depletion, survival, inflammation, and genomic regulation in many biological scenarios. PARP inhibitors (PARPis) have demonstrated efficacy against cancers harboring defective homologous recombination repair pathways, notably those linked to BRCA mutations. PARP1-targeted PET imaging enables patient stratification, treatment assessment, and PARPi pharmacodynamic evaluation in cancers and other pathophysiological conditions. Importantly, PARP1-targeted theranostics have emerged for both diagnostic imaging and therapeutic applications in multiple types of cancers, representing a pivotal advancement in personalized oncology. However, its application in brain tumors is limited by the heterogeneous integrity of the blood brain barrier (BBB) and the blood-tumor barrier. Thus, the development of BBB-penetrant PARP1 tracers remains an unmet need for imaging brain cancers. This review summarizes the current landscape of radiopharmaceuticals and radioligands targeting PARP1, detailing their pharmacological characteristics and potential clinical uses. Furthermore, this review discusses PARP1 tracers that can cross the BBB, underscoring their potential applications in neurooncology and other neurological disorders.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 1-2","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481493","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}