{"title":"Targeting VEGF With 99mTc-Labeled Ranibizumab for Noninvasive Diagnosis of Non-Small Cell Lung Cancer","authors":"Muhammad Shehzad Saleem, Syed Qaiser Shah","doi":"10.1002/jlcr.4150","DOIUrl":"https://doi.org/10.1002/jlcr.4150","url":null,"abstract":"<div>\u0000 \u0000 <p>Angiogenesis, particularly driven by the overexpression of vascular endothelial growth factor (VEGF), plays a crucial role in the growth and metastasis of tumors, making VEGF a significant target in the diagnosis and therapy of non-small cell lung cancer (NSCLC). In this work, the potential of <sup>99m</sup>Tc-labeled ranibizumab was investigated for the non-invasive diagnosis of NSCLC. To that end, ranibizumab (RNB), a VEGF-neutralizing antibody, was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraaza1,4,7,10-tetra(2-carbamoylmethyl) cyclododecane (TCMC) followed by labeling with technetium-99m (<sup>99m</sup>Tc) using different reaction parameters. The <sup>99m</sup>Tc-TCMC-RNB was characterized in terms of the percent radiochemical purity (% RCP) up to 6 h, in vitro stability in serum up to 16 h, internalization kinetics in A549 cells, and biodistribution using the NSCLC Sprague Dawley rat model. The <sup>99m</sup>Tc-labeled TCMC-RNB exhibited 98.3 ± 0.2% RCP in normal saline, stability in rat serum with an overall decay of 32.10% within 18 h, and specific binding to A549 NSCLC cells. Biodistribution studies showed significant tumor uptake. These findings suggest that <sup>99m</sup>Tc-labeled TCMC-RNB holds promise as a specific imaging agent for the diagnosis and monitoring of VEGF-related malignancies, particularly in NSCLC.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 7-8","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171564","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":"Correction to Validation of a Good Manufacturing Practice Procedure for the Production of [11C]AZD4747, a CNS Penetrant KRASG12c Inhibitor","authors":"","doi":"10.1002/jlcr.4149","DOIUrl":"https://doi.org/10.1002/jlcr.4149","url":null,"abstract":"<p>J Labelled Comp Radiopharm. 2024 May 30;67(6):245-249.</p><p>The scheme depicting the labelling of [<sup>11</sup>C]AZD4747 shows the incorrect structure for both the precursor and the product. The position of the nitrogen atom and the stereochemistry of the seven-membered ring have been corrected.</p><p>The corrected reaction scheme is depicted below.<span><!--EMPTY></span></p><p>We apologize for this error.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"68 5-6","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100870","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 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":"https://doi.org/10.1002/jlcr.4147","url":null,"abstract":"<div>\u0000 \u0000 <p>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 [<sup>131</sup>I]<b>1</b> with deuteration on both the <i>N</i>-fluoropropyl and 2<i>β</i>-carbomethoxy positions of the tropane scaffold and then biologically compared with the previously reported analog [<sup>131</sup>I]FP-CIT-d<sub>6</sub> with deuteration only on the <i>N</i>-fluoropropyl group. The radioligand [<sup>131</sup>I]<b>1</b> 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. [<sup>131</sup>I]<b>1</b> exhibited a high in vitro binding affinity for DAT with an IC<sub>50</sub> value of 2.2 nM. Metabolic stability studies demonstrated that [<sup>131</sup>I]<b>1</b> displayed superior in vivo stability compared with [<sup>131</sup>I]FP-CIT-d<sub>6</sub>. Biodistribution studies revealed that [<sup>131</sup>I]<b>1</b> had better DAT affinity, specificity, and a higher target-to-background ratio than [<sup>131</sup>I]FP-CIT-d<sub>6</sub>. Ex vivo autoradiography and blocking experiments validated the selective and reversible binding of [<sup>131</sup>I]<b>1</b> to DAT and superiority to [<sup>131</sup>I]FP-CIT-d<sub>6</sub>. These preliminary results suggest that deuterated radioligand [<sup>131</sup>I]<b>1</b>, with enhanced in vivo stability and higher target-to-background ratio, is a promising DAT probe, warranting the development and application of <sup>123</sup>I-labeled counterpart ([<sup>123</sup>I]<b>1</b>) for SPECT imaging in DAT-related disorders.</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":"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}
{"title":"Synthesis of a Potent Bruton's Tyrosine Kinase Inhibitor Labelled With Carbon-14 and Deuterium","authors":"Bachir Latli, 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, Xin Lv, 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}
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":"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. [<sup>18</sup>F]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 <sup>18</sup>F-labeled <b>1</b> as a radiotracer for our animal PET studies. The first attempt at synthesizing <sup>18</sup>F-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, <sup>18</sup>F-labeled <b>1</b> was eluted without proximate byproducts during chromatographic purification, and routine production of <sup>18</sup>F-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}
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":"<p>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, [<sup>18</sup>F]FEHSP990, suitable for imaging Hsp90 in both brain and tumour tissue. The radiosynthesis of [<sup>18</sup>F]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 <i>K</i><sub><i>i</i></sub> 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.</p>","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}
{"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<sup>th</sup> 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}
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 <p>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 [<sup>18</sup>F]AlF-NY104, a small-molecule CAIX-targeting PET agent in a preclinical ccRCC model. The radiolabeling parameters for [<sup>18</sup>F]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% (<i>n</i> = 3). [<sup>18</sup>F]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 [<sup>18</sup>F]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 [<sup>18</sup>F]AlF-NY104 can be conveniently and efficiently radiolabeled by using an automated module. [<sup>18</sup>F]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 [<sup>18</sup>F]AlF-NY104 in tumors in CAIX-positive models offers an alternative diagnostic strategy for patients with ccRCC.</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":"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}
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 <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 <sup>64</sup>Cu-labeled VEGFR-2–targeted PET dimer tracer [<sup>64</sup>Cu]VEGF<sub>2215</sub> and [<sup>64</sup>Cu]VEGF<sub>2216</sub> 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 [<sup>64</sup>Cu]VEGF<sub>2215</sub> 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, [<sup>64</sup>Cu]VEGF<sub>2216</sub> showed a consistently lower tumor uptake, peaking at only 3.07 ± 0.35 %ID/g. Blocking and biodistribution experiments further confirmed the specificity of [<sup>64</sup>Cu]VEGF<sub>2215</sub> for VEGFR-2. The favorable properties of [<sup>64</sup>Cu]VEGF<sub>2215</sub>, 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}