Journal of labelled compounds & radiopharmaceuticals最新文献

{"title":"25 Years of “Loop” Radiochemistry for PET Imaging","authors":"Emily Murrell,&nbsp;Sahil Khan,&nbsp;Neil Vasdev","doi":"10.1002/jlcr.70029","DOIUrl":"10.1002/jlcr.70029","url":null,"abstract":"<p>While conventional methods to ¹¹C- and ¹⁸F-labelled radiopharmaceuticals utilize a vial-based approach, in the past quarter-century, a modern, efficient, and cleaner “loop method” has been developed. This Perspective will shed light on the history behind the development of the loop radiochemistry method, the multifold advantages associated with the method over other approaches, its applications to the synthesis of ¹¹C- and ¹⁸F-labelled compounds and radiopharmaceuticals for preclinical and human PET imaging studies, its eventual expansion to diverse organic chemistry reactions and finally provide a future outlook for further developments in this field of radiochemistry.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"69 4-6","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673870","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":"Development of a Fully Automated FASTlab 2 Process for [18F]AlF Radiolabelling of NOTA Peptide Conjugates","authors":"Imtiaz Khan,&nbsp;Jon Shales,&nbsp;Stuart McCluskey,&nbsp;Graeme McRobbie,&nbsp;Julian Grigg","doi":"10.1002/jlcr.70030","DOIUrl":"10.1002/jlcr.70030","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Aluminium[¹⁸F]fluoride ([¹⁸F]AlF) radiochemistry offers an attractive alternative to conventional radiometals for peptide and protein labelling and has been applied in several clinical radiopharmaceuticals. The method combines the broad availability of [¹⁸F]fluoride with rapid aqueous-phase labelling under mild conditions, making it well suited to biomolecules sensitive to organic solvents or elevated temperatures. To enable routine clinical translation, we developed a fully automated [¹⁸F]AlF radiolabelling process on the GE HealthCare FASTlab 2 synthesis platform using NOTA-AMBA as a model compound. Formulated [¹⁸F]AlF-NOTA-AMBA was produced with a non–decay-corrected radiochemical yield of 63.3% ± 5.0% (<i>n</i> = 3) in a total synthesis time of 20 min. The radioactive concentration at end of synthesis was 831 ± 115 MBq/mL, with a radiochemical purity of 94.1% ± 0.5%. The molar activity was 183.3 ± 20.7 GBq/μmol. No dissociation of [¹⁸F]AlF from the NOTA chelator was observed over 4 h at room temperature, confirming excellent stability. A simple, rapid and fully automated [¹⁸F]AlF labelling method has been established on FASTlab 2. High yields were achieved using low precursor amounts (95 μg, 67.5 nmol) without HPLC purification. The method is readily adaptable to GMP-compliant production of [¹⁸F]AlF-labelled biomolecules for clinical use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"69 4-6","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645659","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 Carbon-13 and Carbon-14 Labeled BI 690517 (Vicadrostat) and Its O-Glucuronide Metabolite BI 689875","authors":"Bachir Latli,&nbsp;Matt Hrapchak,&nbsp;Maxim Chevliakov,&nbsp;Lalith Samankumara,&nbsp;Saad Khattabi,&nbsp;Nizar Haddad","doi":"10.1002/jlcr.70026","DOIUrl":"10.1002/jlcr.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>Vicadrostat, also known as <b>BI 690517</b> (<b>1</b>) is a novel, potent, and selective aldosterone synthase CYP11B2 inhibitor being developed in combination with empagliflozin to slow the progression of kidney damage and reduce cardiovascular events in people with chronic kidney diseases (CDK). The stable isotope labeled <b>BI 690517</b> was obtained in a 12-step synthesis starting from aniline-¹³<i>C</i>₆. The product was isolated with high chemical purity and enantiomeric excess. Carbon-14 labeled <b>BI 690517</b> was prepared in one radioactive step from a chiral iodo-analog <b>BI 764437</b> and zinc cyanide-¹⁴<i>C</i>. [^<b>14</b><b>C]-1</b> was obtained with a specific activity of 55.6 mCi/mmol (2.05 GBq/mmol), chemical and radiochemical purities higher than 98%, and with enantiomeric excess higher than 99%. Vicadrostat undergoes extensive hepatic glucuronidation to form the <i>O</i>-glucuronide <b>BI 689875</b> (<b>2</b>). Both carbon-13 and carbon-14 labeled <b>BI 689875</b> were also synthesized.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"69 4-6","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627937","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":"Radiotheranostics With Nanoparticles: Precision Targeting in Receptor-Overexpressing Tumors","authors":"Evalyne J. Cheruiyot,&nbsp;David M. Wanjeh,&nbsp;John K. Birir,&nbsp;Susan W. Karuga,&nbsp;Beatrice K. Amugune,&nbsp;Claudia G. Chambers,&nbsp;Michael R. Lewis,&nbsp;Charles J. Smith,&nbsp;Tamer M. Sakr","doi":"10.1002/jlcr.70028","DOIUrl":"10.1002/jlcr.70028","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer remains one of the most challenging medical conditions. Nanotechnology is revolutionizing the approach to cancer management as an efficient tool for early diagnosis, therapy and monitoring. Nanoparticles (NPs) have shown promising results in advancing precision medicine by integrating diagnostic imaging and targeted therapy within a single platform, a concept of theranostics. Nanocarriers are synthesized via the use of biocompatible materials that are functionalized with specific ligands that bind to receptors that are overexpressed on the surface of cancer cells. For theranostic purposes, these NPs are loaded with suitable radioisotopes that emit gamma, positron, alpha or beta radiation for imaging and/or therapy. Despite the significant successes, most of the work is still at the preclinical stages awaiting clinical translation. In this review, a comprehensive examination of the current state of receptor-targeted radiotheranostic NPs is presented, with a focus on their design, functionalization, receptor-specific targeting, and clinical translational potential. The role of key tumor markers is highlighted in guiding NP delivery and improving precision and therapy. The exploration of these cutting-edge advancements and associated challenges will provide insights into the revolution of radiotheranostic nanomedicine and its impact on the future of precision oncology.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"69 4-6","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627928","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":"Abstracts From the 31st International Isotope Society UK Meeting 14th November 2025.","authors":"","doi":"10.1002/jlcr.70024","DOIUrl":"https://doi.org/10.1002/jlcr.70024","url":null,"abstract":"","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"69 4-6","pages":"e70024"},"PeriodicalIF":0.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773949","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":"RETRACTION: Enhanced Control of Bacterial Wilt Disease in Tomato Plant via Transport and Penetration Tracking by Aid of 99mTc-Labeled Ralstonia solanacearum–Specific Bacteriophage","authors":"","doi":"10.1002/jlcr.70027","DOIUrl":"10.1002/jlcr.70027","url":null,"abstract":"<p><b>RETRACTION</b>: M. H. Abdel-Aal, Y. A. Hasanien, N. A. Younis, G. El Didamony, A. Askora, and G. Abdelaziz, “Enhanced Control of Bacterial Wilt Disease in Tomato Plant via Transport and Penetration Tracking by Aid of ^99mTc-Labeled <i>Ralstonia solanacearum</i>–Specific Bacteriophage,” <i>Journal of Labelled Compounds and Radiopharmaceuticals</i> 68, no. 13 (2025): e4169, https://doi.org/10.1002/jlcr.4169.</p><p>The above article, published online on 11 November 2025 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, V Derdau; and John Wiley &amp; Sons Ltd. The retraction has been agreed upon following concerns raised by a third party. A subsequent investigation confirmed several deficiencies in the study, including the absence of essential controls, replicates, and appropriate statistical analysis. In addition, in Figure 3, the Ral 10, Ral 9, Ral 8 and Ral 7 bands appear to be duplicated, and there is evidence that Ral 10 has been spliced into the image. Furthermore, the images shown in Figures 12A and 12C are identical, despite representing untreated and treated plants. The authors cooperated with the investigation and explained that Figure 3 combines two images from separate experimental runs, as the gel tank could not hold all samples simultaneously. However, they were unable to provide the original images and did not comment on the duplicated bands. The authors also explained that the duplication in Figure 12 was an error due to figure mismanagement; they provided an alternative image for Figure 12C. However, this was not satisfactory to address all the concerns. As a result, the editors determined that the results cannot be validated and therefore the conclusions of the study are unreliable. The authors disagree with the retraction.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"69 4-6","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521133","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, Radiochemical Characterization, and Biodistribution of a 188Re Analogue of [131I]mIBG in a Neuroblastoma Xenograft Model","authors":"Navin Sakhare,&nbsp;Dheeraj Kumar,&nbsp;Soumen Das,&nbsp;Arpit Mitra,&nbsp;Shubhangi Mirapurkar,&nbsp;G. Rani,&nbsp;M. Sheela,&nbsp;Viju Chirayil,&nbsp;Bhabani Mohanty,&nbsp;Anupam Mathur,&nbsp;Madhava B. Mallia,&nbsp;Pradip Chaudhari","doi":"10.1002/jlcr.70025","DOIUrl":"10.1002/jlcr.70025","url":null,"abstract":"<p>[¹³¹I]meta-iodobenzylguanidine (mIBG) in variable dosage forms is widely used for the therapy of neuroendocrine tumors. Our group previously reported a ^99mTc analogue of [¹³¹I]mIBG that demonstrated high specificity in vitro towards norepinephrine transporter (NET)–positive neuroblastoma cells. Considering that the ^99mTc/¹⁸⁸Re pair serves as a useful theranostic combination, we herein describe the synthesis of its ¹⁸⁸Re analogue and evaluate its potential for therapeutic applications. A benzylguanidine derivative functionalized at the <i>meta</i> position via an isonitrile moiety (“<b>1</b>”) was employed for ¹⁸⁸Re complexation following Re-“4 + 1” chemistry. Synthesized ¹⁸⁸Re complex <b>6</b> was evaluated in NET-positive SK-N-SH neuroblastoma cells and corresponding xenograft models. Cellular uptake studies revealed that the ¹⁸⁸Re complex <b>6</b> exhibited ~50% of the uptake observed for [¹²⁵I]mIBG. Nonetheless, it retained significant NET specificity (~60%), as confirmed by inhibition experiments using desmethylimipramine (DMI). Biodistribution studies in SK-N-SH xenograft-bearing mice demonstrated tumor uptake of 4.07 ± 0.08%ID/g at 30 min (<i>p</i> &gt; 0.05), with significant retention up to 3 h (4.99 ± 0.08%ID/g). Tumor uptake was shown to be NET-specific, as pre-treatment with excess DMI significantly inhibited tracer accumulation in vivo. Bioevaluation of the synthesized ¹⁸⁸Re complex <b>6</b> confirmed its affinity for NETs; however, limited in vivo stability restricted its suitability for therapeutic application.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"69 3","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12995507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474025","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 Characterization of Deuterated Detomidine for Use in Equine Medication Regulation","authors":"Justin C. Holmes,&nbsp;Adedamola S. Arojojoye,&nbsp;Samuel G. Awuah,&nbsp;Rodney Eisenberg,&nbsp;Clara K. Fenger,&nbsp;George A. Maylin,&nbsp;Kimberly Brewer,&nbsp;Thomas Tobin","doi":"10.1002/jlcr.70023","DOIUrl":"10.1002/jlcr.70023","url":null,"abstract":"<div>\u0000 \u0000 <p>Detomidine, 5-[(2,3-dimethylphenyl)methyl]-1<i>H</i>-imidazole, is a tranquilizer/sedative/analgesic widely used in equine medicine and regulated by several different analyte concentrations of detomidine and its hydroxydetomidine and carboxydetomidine metabolites in plasma and urine. Accurate regulatory quantitation of detomidine at low picogram/mL concentrations requires the availability of a stable isotope internal standard of detomidine; however, to the best of our knowledge, no certified deuterated internal standard of detomidine is commercially available and its synthesis has not been reported. Here, we report the first synthesis and characterization of detomidine-<i>d</i>, prepared in six sequential steps consisting of a deuterium–hydrogen exchange, diazotization, Grignard coupling, hydrogenolysis, and palladium-catalyzed deuterium–hydrogen exchange. This overall route gave detomidine-<i>d</i> in moderate chemical yield with each intermediate purified to &gt; 90% purity as determined by RP-HPLC. Regiochemistry and isotopic enrichment were confirmed by ¹H NMR and LC/MS, demonstrating a viable method for the incorporation of three deuterium atoms into the detomidine scaffold. This internal standard will allow for precise LC/MS quantitation of detomidine at regulatory threshold concentrations, enabling accurate detection and quantitation of picogram/mL concentrations in equine blood and urine samples, thereby supporting regulatory compliance for equine medication control programs.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"69 3","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468199","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":"Dosimetric Development of Yttrium-90 Resin Microspheres for Selective Internal Radiation Therapy: Current Status and Perspectives","authors":"Zhong-Bin Hang,&nbsp;Hai Hu,&nbsp;Zi-Wei Liang,&nbsp;Yan Zhang,&nbsp;Chen-Yu Yan,&nbsp;Tian-Tian Zhang,&nbsp;Ke-Xin Wei,&nbsp;Ming-Zhe Song,&nbsp;Jing Wu,&nbsp;Zuo-Xiang He","doi":"10.1002/jlcr.70022","DOIUrl":"10.1002/jlcr.70022","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;p&gt;Yttrium-90 resin microspheres selective internal radiation therapy (&lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msup&gt;\u0000 &lt;mrow&gt;&lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mn&gt;90&lt;/mn&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msup&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {}^{90} $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;Y-SIRT) has been increasingly adopted worldwide as a locoregional treatment option for appropriately selected patients with liver malignancies. The key to ensuring that the tumor receives an adequate radiation dose while minimizing the dose to normal tissues is to optimize the trade-off between tumor control and the probability of normal tissue complications. To accurately determine a patient's internal radiation dose, pre-treatment dose planning and post-treatment dose verification using dosimetric methods are recommended and increasingly considered best practice in &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msup&gt;\u0000 &lt;mrow&gt;&lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mn&gt;90&lt;/mn&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msup&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {}^{90} $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;Y-SIRT, where feasible. Due to the increased demand for personalized treatment and dose accuracy in clinical practice, &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msup&gt;\u0000 &lt;mrow&gt;&lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mn&gt;90&lt;/mn&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msup&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {}^{90} $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;Y-SIRT dosimetry has transitioned from organ-level to voxel-level dosimetry. This paper introduces the relevant principles and development history of &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msup&gt;\u0000 &lt;mrow&gt;&lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mn&gt;90&lt;/mn&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msup&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {}^{90} $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;Y-SIRT dosimetry for resin microspheres. It also discusses the clinical performance, influencing factors and practical applications of relevant dosimetry methods. These include body surface area (BSA) method, MIRD multi-compartment model method, and partition model method; voxel-S-value (VSV); local deposition method (LDM); and Monte Carlo (MC) method. Finally, it covers the subsequent development of resin microsphere &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msup&gt;\u0000 &lt;mrow&gt;&lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mn&gt;90&lt;/mn&gt;\u0000 &lt;/mrow&gt;\u0000 ","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"69 3","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344533","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":"Preclinical Evaluation of [225Ac]Ac–Sibrotuzumab Employing a PEG4–Macropa Site-Specific Chelation Strategy for Targeted Ablation of Cancer-Associated Fibroblasts in Desmoplastic Tumors","authors":"Syed Qaiser Shah,&nbsp;Ralph Santos-Oliveira,&nbsp;Madeeha Shabnam,&nbsp; DeryaIlem-Ozdemir","doi":"10.1002/jlcr.70020","DOIUrl":"10.1002/jlcr.70020","url":null,"abstract":"<div>\u0000 \u0000 <p>Fibroblast activation protein is highly expressed in tumor-associated fibroblasts and represents a promising stromal target for cancer therapy. Actinium-225 (²²⁵Ac) offers potent α-emissions for targeted radiotherapy but requires exceptionally stable chelation. We report the synthesis and preclinical evaluation of the novel FAP-targeted α-immunoconjugate [²²⁵Ac]Ac–Macropa–PEG₄–Sibrotuzumab. Sibrotuzumab was site-specifically modified with Macropa–PEG₄ and radiolabeled with ²²⁵Ac under mild conditions. Radiochemical purity, serum stability, and immunoreactivity were assessed by radio-iTLC, SEC–HPLC, and FAP⁺/FAP⁻ cell assays. In vivo biodistribution and therapeutic efficacy were evaluated in NIH/3T3-FAP⁺ xenograft–bearing mice. The radioconjugate was obtained in 78.5% ± 2.2% yield with &gt; 98% radiochemical purity and &gt; 90% stability over 7 days. The immunoreactive fraction was 88.7%, and the construct demonstrated strong FAP-specific uptake with ~30% internalization at 24 h. In vivo, [²²⁵Ac]Ac–Macropa–PEG₄–Sibrotuzumab showed high tumor accumulation (24.1 ± 1.6 %ID/g at 168 h), rapid clearance from normal tissues, and minimal bone uptake. Treatment achieved ~62% tumor growth inhibition, prolonged survival beyond 28 days, and induced partial (50%) or complete (17%) responses without systemic toxicity. These findings highlight Macropa as a robust chelation strategy and support Sibrotuzumab-based α-immunoconjugates for precise targeting of FAP-positive desmoplastic tumors.</p>\u0000 </div>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"69 2","pages":""},"PeriodicalIF":0.9,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157242","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}