Journal of labelled compounds & radiopharmaceuticals最新文献

Development and Validation of an HPLC Method to Determine Chemical and Radiochemical Purity of [18F]Florbetazine Injection

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-03-18 DOI: 10.1002/jlcr.4140

Fuhai Wu, Xiaoming Wang, Huan Chen, Xu Zhou, Hailong Zhao, Mengchao Cui

{"title":"Development and Validation of an HPLC Method to Determine Chemical and Radiochemical Purity of [18F]Florbetazine Injection","authors":"Fuhai Wu, Xiaoming Wang, Huan Chen, Xu Zhou, Hailong Zhao, Mengchao Cui","doi":"10.1002/jlcr.4140","DOIUrl":"https://doi.org/10.1002/jlcr.4140","url":null,"abstract":"<div>\u0000 \u0000 [18F]Florbetazine injection, a radiotracer that could target Aβ plaques and achieve diagnosis of Alzheimer's disease (AD), is a novel positron emission tomography (PET) imaging agent currently in the investigational new drug (IND) application stage. The active ingredient of [18F]Florbetazine injection, [18F]Florbetazine, is a diaryl-azine derivative. Chemical and radiochemical purity is critical quality attributes (CQAs) for [18F]Florbetazine injection, and thus, we have developed and validated a relevant HPLC method. This study describes the specificity, linearity, accuracy, repeatability, and limit of quantification (LOQ) of the HPLC method. The stability of three sample batches was investigated using the established method. The validation results demonstrated the accuracy, precision, and sensitivity of the method, making it suitable for implementation as part of the quality control (QC) process for [18F]Florbetazine injection. The stability of three sample batches revealed a decrease in concentration and radiochemical purity over 10 h. However, all samples maintained a radiochemical purity of over 90% after 10 h. The results provided a foundation for establishing quality standards for [18F]Florbetazine injection. The same methodology employed in this study could be applied and modified for QC protocols of other 18F-labeled radiopharmaceuticals.\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 3","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645889","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

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

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-03-17 DOI: 10.1002/jlcr.4143

Chao-Cheng Chen, Lei Wang, Antonio A. W. L. Wong, Wing Sum Lau, Pauline Ng, Helen Merkens, François Bénard, Kuo-Shyan Lin

{"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, Lei Wang, Antonio A. W. L. Wong, Wing Sum Lau, Pauline Ng, Helen Merkens, François Bénard, Kuo-Shyan Lin","doi":"10.1002/jlcr.4143","DOIUrl":"https://doi.org/10.1002/jlcr.4143","url":null,"abstract":"<div>\u0000 \u0000 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/vivo 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 (n = 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 N-(4-quinolinoyl)-Gly-(2-azabicyclo[3.1.0]hexane-3-carbonitrile) is a promising pharmacophore for the design of FAP-targeted tracers.\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}

引用次数: 0

Synthesis and Imaging of Novel CDK19-Targeted Tracers Incorporating an Albumin-Binding Moiety

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-03-12 DOI: 10.1002/jlcr.4130

Panfeng Li, Zhao Yang, Yanli Li, Jiang Yu, Ziyang Wang, Jiaci Nie, Xiaoman Liu, Wenbin Hou, Yu Zhao, Dong Dai, Yiliang Li

引用次数: 0

Preparation of Macrobicyclic Cryptands for Radiometal Complexation

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-03-05 DOI: 10.1002/jlcr.4136

Laura Höffmann, Magdalena Blei, Falco Reissig, Klaus Kopka, Constantin Mamat

引用次数: 0

Synthesis and Characterization of 3-Hydroxybupivacaine and Deuterated 3-Hydroxybupivacaine for Use in Equine Medication Regulation

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-03-04 DOI: 10.1002/jlcr.4132

Adedamola S. Arojojoye, Justin Holmes, Miles P. Buchart, Samuel G. Awuah, Rodney Eisenberg, Clara K. Fenger, George A. Maylin, Thomas Tobin

{"title":"Synthesis and Characterization of 3-Hydroxybupivacaine and Deuterated 3-Hydroxybupivacaine for Use in Equine Medication Regulation","authors":"Adedamola S. Arojojoye, Justin Holmes, Miles P. Buchart, Samuel G. Awuah, Rodney Eisenberg, Clara K. Fenger, George A. Maylin, Thomas Tobin","doi":"10.1002/jlcr.4132","DOIUrl":"https://doi.org/10.1002/jlcr.4132","url":null,"abstract":"<div>\u0000 \u0000 Bupivacaine is a local anesthetic widely used in equine and human medicine. Use of bupivacaine in performance horses is regulated because its ability to block pain means that it can be misused for advantage in performance horses. In racing regulation, bupivacaine is classified by the Association of Racing Commissioners International (ARCI) as a Class 2 Penalty Class A Foreign substance, the detection of which can lead to significant penalties. In horses, bupivacaine is metabolized by Phase-I hydroxylation to yield 3-hydroxybupivacaine, which is then glucuronidated to yield the Phase-II metabolite bupivacaine-3-hydroxyglucuronide, which is excreted at relatively high concentrations in equine urine. Standard regulatory procedure during urinalysis is to perform an enzymatic hydrolysis, thereby enabling subsequent detection of 3-hydroxybupivacaine, the primary analyte used for bupivacaine regulation in urine samples from competition horses. We now report on the synthesis of 3-hydroxybupivacaine and deuterated 3-hydroxybupivacaine from piperidine-2-carboxylic acid in six successive steps with moderate yield. The compounds were characterized by 1H and 13C NMR and their purity ascertained by HPLC-MS. The deuterated bupivacaine and 3-hydroxybupivacaine were further confirmed by HRMS. The synthesis of these compounds provides certified reference standards and stable isotope-labeled internal standards for drug testing in competitive equine sports including horse racing.\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 3","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533519","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

Synthesis of 14C-Labeled Polyethylene Terephthalate and Generation of 14C-Nanoparticles for Fate and Disposition Studies

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-03-04 DOI: 10.1002/jlcr.4137

Anuradha Singh, Weilin L. Shelver, David J. Smith

{"title":"Synthesis of 14C-Labeled Polyethylene Terephthalate and Generation of 14C-Nanoparticles for Fate and Disposition Studies","authors":"Anuradha Singh, Weilin L. Shelver, David J. Smith","doi":"10.1002/jlcr.4137","DOIUrl":"https://doi.org/10.1002/jlcr.4137","url":null,"abstract":"<div>\u0000 \u0000 Polyethylene terephthalate (PET) is one of the most extensively used plastics in daily life. Due to its prevalent use, it is ubiquitous in the environment and a significant contributor to plastic pollution. Continuous exposure to photochemical, thermal, biological, and mechanical processes makes PET susceptible to slow degradation and the production of microsized and/or nanosized particles known as PET microplastic/nanoplastic (MP/NP). MP/NP are widely detected in the environment, including in drinking water and human food; consequently, knowledge gaps on the impacts of MP/NP in human food sources have gained global attention. A large knowledge gap is the bioaccumulation and fate of PET MP/NP in food animals. The application of carbon-14 labeled PET NP in food animals would provide a relatively straightforward approach to understanding the degree of PET absorption and its tissue distribution after absorption. Here, a simple, fast, and efficient synthetic method is described to produce [14C]-PET NP. The method comprises the polycondensation of terephthaloyl chloride and readily accessible [14C]-ethylene glycol followed by nanoprecipitation. The synthesized [14C]-PET and [14C]-PET NP were characterized by nuclear magnetic resonance spectroscopy (NMR), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering spectroscopy, thermogravimetric analyzer (TGA), and UV-Vis spectroscopy.\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 3","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554436","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

Automated Radiolabeling and Evaluation of [18F]FPMBBG: A Novel Cardiac Neuronal PET Imaging Agent

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-03-04 DOI: 10.1002/jlcr.4139

Min Ju, Wanjie Ren, Zongyao Zhang, Jie Lu, Kai Han, Lei Wang, Wei Fang

{"title":"Automated Radiolabeling and Evaluation of [18F]FPMBBG: A Novel Cardiac Neuronal PET Imaging Agent","authors":"Min Ju, Wanjie Ren, Zongyao Zhang, Jie Lu, Kai Han, Lei Wang, Wei Fang","doi":"10.1002/jlcr.4139","DOIUrl":"https://doi.org/10.1002/jlcr.4139","url":null,"abstract":"<div>\u0000 \u0000 This study reports the automated radiosynthesis and evaluation of [18F]FPMBBG, a radiopharmaceutical designed to target the norepinephrine transporter (NET). A newly developed fully protected benzylguanidine precursor, which prevents interference from non-protected benzylguanidine part during the nucleophilic process, has enabled a one-pot two-step fully automated cassette-based synthesis of [18F]FPMBBG. This advancement enhances the feasibility of the synthesis, ensures reproducibility, and allows for the production of substantial quantities of the radiotracer, paving the way for future clinical applications. [18F]FPMBBG was prepared in radiochemical yield of ~ 23% (n = 6, decay-corrected) within 70 min, with a radiochemical purity exceeding 98%, and molar activity of > 2 GBq/μmol. In studies using miniature Bama pigs, [18F]FPMBBG showed favorable distribution, providing high-contrast cardiac images at an early stage. Moreover, desipramine inhibition studies confirmed the high NET specificity of [18F]FPMBBG. The efficient automated synthesis, robust heart uptake, and minimal background signal highlight [18F]FPMBBG as a promising PET tracer for assessing cardiac sympathetic neuronal function.\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 3","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533520","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

Synthesis and Preclinical Evaluation of Peptide Dimer-Based PET Tracers for Imaging VEGFR-2 Expression in Tumors.

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-03-01 DOI: 10.1002/jlcr.4138

He Wenjun, Chen Xueyao, Cai Qijun, Li Yingxin, Ran Bingyu, Cao Xiaoling, Cheng Yong, Jiang Yuanfang, Hou Lu, Ma Jie, Ye Weijian, Zhang Siqi, Wang Lu, Xu Hao, Hu Kuan, Shang Jingjie

{"title":"Synthesis and Preclinical Evaluation of Peptide Dimer-Based PET Tracers for Imaging VEGFR-2 Expression in Tumors.","authors":"He Wenjun, Chen Xueyao, Cai Qijun, Li Yingxin, Ran Bingyu, Cao Xiaoling, Cheng Yong, Jiang Yuanfang, Hou Lu, Ma Jie, Ye Weijian, Zhang Siqi, Wang Lu, Xu Hao, Hu Kuan, Shang Jingjie","doi":"10.1002/jlcr.4138","DOIUrl":"https://doi.org/10.1002/jlcr.4138","url":null,"abstract":"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.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 3","pages":"e4138"},"PeriodicalIF":0.9,"publicationDate":"2025-03-01","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}

引用次数: 0

Design and Synthesis of a 18F-Radiolabeled Pyrrolo[2,3-d]pyrimidine Ligand as a CSF1R Receptor PET Imaging Agent

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-02-24 DOI: 10.1002/jlcr.4131

Srinivasulu Cherukupalli, Morten Karlsen, Bård Helge Hoff, Eirik Sundby

{"title":"Design and Synthesis of a 18F-Radiolabeled Pyrrolo[2,3-d]pyrimidine Ligand as a CSF1R Receptor PET Imaging Agent","authors":"Srinivasulu Cherukupalli, Morten Karlsen, Bård Helge Hoff, Eirik Sundby","doi":"10.1002/jlcr.4131","DOIUrl":"https://doi.org/10.1002/jlcr.4131","url":null,"abstract":"<div>\u0000 \u0000 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-d]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 (K2.2.2)-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-d]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.\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}

引用次数: 0

Current Advances in PARP1-Targeted Theranostics

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-02-24 DOI: 10.1002/jlcr.4135

Jie Tong, Baosheng Chen, Tommaso Volpi, Yawen Li, Paul A. Ellison, Zhengxin Cai

{"title":"Current Advances in PARP1-Targeted Theranostics","authors":"Jie Tong, Baosheng Chen, Tommaso Volpi, Yawen Li, Paul A. Ellison, Zhengxin Cai","doi":"10.1002/jlcr.4135","DOIUrl":"https://doi.org/10.1002/jlcr.4135","url":null,"abstract":"<div>\u0000 \u0000 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.\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}

引用次数: 0