Journal of labelled compounds & radiopharmaceuticals最新文献_第3页

Synthesis and Preliminary Evaluation of an In Vivo Stable 131I-Labeled Deuterated Tropane for Mapping Dopamine Transporter 体内稳定的131 - i标记氘化Tropane的合成及初步评价

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-05-05 DOI: 10.1002/jlcr.4147

Jiaojiao Zuo, Jing Kang, Jingjing Hong, Jingwen Li, Yi Fang, Chunyi Liu, Minhao Xie, Zhengping Chen

{"title":"Synthesis and Preliminary Evaluation of an In Vivo Stable 131I-Labeled Deuterated Tropane for Mapping Dopamine Transporter","authors":"Jiaojiao Zuo, Jing Kang, Jingjing Hong, Jingwen Li, Yi Fang, Chunyi Liu, Minhao Xie, Zhengping Chen","doi":"10.1002/jlcr.4147","DOIUrl":"10.1002/jlcr.4147","url":null,"abstract":"<div>\u0000 \u0000 Dopamine transporter (DAT) is closely associated with neurodegenerative diseases such as Parkinson's disease (PD). To develop an in vivo stable radioligand targeting DAT, we synthesized a novel iodine-131-labeled tropane analog [131I]1 with deuteration on both the N-fluoropropyl and 2β-carbomethoxy positions of the tropane scaffold and then biologically compared with the previously reported analog [131I]FP-CIT-d6 with deuteration only on the N-fluoropropyl group. The radioligand [131I]1 was obtained via a radioiodine-destannylation reaction with a radiochemical yield of ~95%, a radiochemical purity of > 99% and a molar activity of 12.72 GBq/μmol. [131I]1 exhibited a high in vitro binding affinity for DAT with an IC50 value of 2.2 nM. Metabolic stability studies demonstrated that [131I]1 displayed superior in vivo stability compared with [131I]FP-CIT-d6. Biodistribution studies revealed that [131I]1 had better DAT affinity, specificity, and a higher target-to-background ratio than [131I]FP-CIT-d6. Ex vivo autoradiography and blocking experiments validated the selective and reversible binding of [131I]1 to DAT and superiority to [131I]FP-CIT-d6. These preliminary results suggest that deuterated radioligand [131I]1, with enhanced in vivo stability and higher target-to-background ratio, is a promising DAT probe, warranting the development and application of 123I-labeled counterpart ([123I]1) for SPECT imaging in DAT-related disorders.\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":"143909295","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 18F-Labeled FC-119S and Its Tosyl Precursor 18f标记FC-119S的合成及其Tosyl前体

IF 0.9 4区医学

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2025-05-05 DOI: 10.1002/jlcr.4145

Koichi Kato, Makoto Funasaka, Jun Ogura, Eiko N. Minakawa, Kazuhiko Seki, Takuya Kumamoto

{"title":"Synthesis of 18F-Labeled FC-119S and Its Tosyl Precursor","authors":"Koichi Kato, Makoto Funasaka, Jun Ogura, Eiko N. Minakawa, Kazuhiko Seki, Takuya Kumamoto","doi":"10.1002/jlcr.4145","DOIUrl":"10.1002/jlcr.4145","url":null,"abstract":"<div>\u0000 \u0000 Animal models of Alzheimer's disease (AD) 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 AD, namely, the deposition of amyloid β peptide (Aβ) in the brain. [18F]FC-119S (1), a 2-pyridylbenzothiazole analog, has been applied as a radiotracer for PET visualization of Aβ plaques in an AD model, the 5xFAD mouse. Here, we present an alternative method for the automated synthesis of 18F-labeled 1 as a radiotracer for our animal PET studies. The first attempt at synthesizing 18F-labeled 1 using a mesyl precursor afforded desired product 1, although a nonfluorinated mesyl byproduct was eluted prior to 1 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 1 was eluted without proximate byproducts during chromatographic purification, and routine production of 18F-labeled 1 was achieved for our AD studies using animal models.\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}

引用次数: 0

Radiosynthesis and Evaluation of [18F]FEHSP990 as Novel PET Tracer for Hsp90 PET Imaging [18F]FEHSP990作为Hsp90 PET显像新型示踪剂的放射性合成与评价

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":"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 同位素在法医学中的应用

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 [18F]半标记NY104的合成、临床前表征及影像学研究

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":"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 基于肽二聚体的PET示踪剂在肿瘤中VEGFR-2表达成像的合成及临床前评价

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 高效液相色谱法测定[18F]Florbetazine注射液化学和放射化学纯度的建立与验证

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":"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 一种新型68ga标记的2-Azabicyclo[3.1.0]己烷-3-碳腈基成纤维细胞激活蛋白靶向示踪剂用于癌症正电子发射断层成像

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":"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 含有白蛋白结合片段的新型cdk19靶向示踪剂的合成和成像

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 放射性金属络合用大双环密码物的制备

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