Journal of labelled compounds & radiopharmaceuticals最新文献

Radiosynthesis and Evaluation of [18F]FEHSP990 as Novel PET Tracer for Hsp90 PET Imaging

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-04-11 DOI: 10.1002/jlcr.4144

Romy Cools, Koen Vermeulen, Sofie Celen, Renan C. F. Leitao, Guy Bormans

{"title":"Radiosynthesis and Evaluation of [18F]FEHSP990 as Novel PET Tracer for Hsp90 PET Imaging","authors":"Romy Cools, Koen Vermeulen, Sofie Celen, Renan C. F. Leitao, Guy Bormans","doi":"10.1002/jlcr.4144","DOIUrl":"https://doi.org/10.1002/jlcr.4144","url":null,"abstract":"Heat shock protein 90 (Hsp90) is a critical chaperone in the protein quality control system, essential for maintaining cellular proteostasis. Aberrant Hsp90 function has been implicated in cancer and neurodegenerative disorders, making it an attractive therapeutic target and a potential biomarker for disease characterisation and progression using PET imaging. In this study, we aimed to develop the first fluorine-18 labelled brain permeable PET imaging agent, [18F]FEHSP990, suitable for imaging Hsp90 in both brain and tumour tissue. The radiosynthesis of [18F]FEHSP990 was achieved with a radiochemical yield of 48 ± 29%, high radiochemical purity of > 99% and a molar activity of 213 ± 101 GBq/μmol at the end of synthesis. Competition binding studies in healthy mouse brain homogenate samples indicated a Ki value of approximately 200 nM. In vitro tracer binding to rodent brain and glioblastoma tumour tissue slices was high and deemed Hsp90-specific, as demonstrated by autoradiography blocking studies, whereas binding to living glioblastoma U87 cells was notably low. Ex vivo biodistribution and in vivo PET imaging studies in healthy rodents demonstrated limited brain exposure of the tracer, potentially due to insufficient affinity for Hsp90 and/or restricted blood–brain barrier permeability. Further development of fluorine-18 labelled Hsp90 tracers is warranted.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 4","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821991","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

Applications of Isotopes in Forensic Science

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-03-28 DOI: 10.1002/jlcr.4141

Crist N. Filer

引用次数: 0

Synthesis, Preclinical Characterizations and Imaging Studies of [18F]AlF-Labeled NY104, a CAIX-Targeting Diagnostic Agent

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-03-28 DOI: 10.1002/jlcr.4142

Yu Huang, Waisi Eng, Chong Shao, Gaoliang Cheng, Changwu Qiang, Wei Peng, Si Yang, Shiguo Liu

{"title":"Synthesis, Preclinical Characterizations and Imaging Studies of [18F]AlF-Labeled NY104, a CAIX-Targeting Diagnostic Agent","authors":"Yu Huang, Waisi Eng, Chong Shao, Gaoliang Cheng, Changwu Qiang, Wei Peng, Si Yang, Shiguo Liu","doi":"10.1002/jlcr.4142","DOIUrl":"https://doi.org/10.1002/jlcr.4142","url":null,"abstract":"<div>\u0000 \u0000 The protein carbonic anhydrase IX (CAIX) is highly expressed in clear cell renal cell carcinoma (ccRCC), and its restrictive expression in healthy tissues makes CAIX an attractive diagnostic target. The purpose of this study was to synthesize and evaluate [18F]AlF-NY104, a small-molecule CAIX-targeting PET agent in a preclinical ccRCC model. The radiolabeling parameters for [18F]AlF-NY104 have been optimized, including the solvent volume and reaction temperature. The high-purity product was synthesized by using an automated multifunctional module Mortenon M1, leading to nondecay-corrected radiochemical yields over 50% (n = 3). [18F]AlF-NY104 showed excellent tumor targeting capability and afforded high-quality microPET/CT imaging in the OS-RC-2 tumor model (15.01 ± 0.76 %ID/g [mean ± SEM]). The radiation exposure from [18F]AlF-NY104 is estimated to be 4.44 mSv for adult male and female human subjects, which is well below the FDA recommended whole-body single exposure limit of 30 mSv. Our investigation revealed that [18F]AlF-NY104 can be conveniently and efficiently radiolabeled by using an automated module. [18F]AlF-NY104 exhibited many outstanding properties, such as rapid uptake in tumor, rapid clearance through the kidney, and low uptake in most normal organs. Moreover, the high accumulation of [18F]AlF-NY104 in tumors in CAIX-positive models offers an alternative diagnostic strategy for patients with ccRCC.\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":"143717268","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 : 2025-03-20 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":"10.1002/jlcr.4138","url":null,"abstract":"<div>\u0000 \u0000 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.\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}

引用次数: 0

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