EJNMMI Radiopharmacy and Chemistry最新文献

{"title":"Drug interactions involving therapeutic radiopharmaceuticals: a systematic review","authors":"Robin Gacon,&nbsp;Romane Chapuis,&nbsp;Luca Fabris-Davet,&nbsp;Nina Ranjit,&nbsp;Sylvain Goutelle,&nbsp;Laurent Bourguignon,&nbsp;Anthime Flaus,&nbsp;Claire Bolot,&nbsp;Elise Levigoureux,&nbsp;Matthieu Gallet,&nbsp;Sarah Chaib","doi":"10.1186/s41181-025-00395-y","DOIUrl":"10.1186/s41181-025-00395-y","url":null,"abstract":"<div><h3>Background</h3><p>Drug interactions with diagnostic radiopharmaceuticals are well recognized, as they can modify biodistribution and lead to false or misleading diagnostic results. However, little is known about such interactions in the field of therapeutic radiopharmaceuticals, despite their rapid expansion—particularly with targeted radionuclide therapies such as Radioligand Therapy (RLT). This review aims, for the first time, to systematically compile and analyze available data on drug interactions involving therapeutic radiopharmaceuticals, in order to support safer and more effective patient care.</p><h3>Main body</h3><p>Eighty-three articles investigating drug interactions with [¹⁷⁷Lu]Lu-oxodotreotide (Lutathera®), [¹⁷⁷Lu]Lu-vipivotide tetraxetan (Pluvicto®), [¹³¹I]INa, [¹³¹I]I-meta-iodobenzylguanidine ([¹³¹I]I-MIBG), [²²³Ra]RaCl₂ (Xofigo®), [⁹⁰Y]Y-ibritumomab tiuxetan (Zevalin®) or [¹⁵³Sm]Sm-lexidronam pentasodium (Quadramet®) were included. These studies reported 133 drug interactions, 69% of which were not mentioned in the corresponding summaries of product characteristics. Interactions could be beneficial (e.g., reducing renal toxicity) or harmful (e.g., decreasing therapeutic efficacy or potentiating toxicity). Three interactions involved complementary and alternative medicines (quercetin, Ginkgo biloba and ouabain).</p><p>Overall, the evidence level for reported interactions was low: 88% were classified as level 3 or 4 according to the Centre for Evidence-Based Medicine (CEBM) scale.</p><h3>Conclusion</h3><p>Drug interactions with therapeutic radiopharmaceuticals remain underreported, yet they may have significant clinical consequences. Clinical radiopharmacy plays a key role in detecting and preventing these interactions. Radiopharmacists, through their expertise, can identify potential interactions, influence therapeutic decisions, and positively impact patient management. Their involvement throughout the care pathway is essential to ensure the safe and effective use of these innovative therapies. Nuclear medicine physicians should also be aware that such interactions can alter biodistribution, compromise therapeutic efficacy, and increase the risk of adverse effects.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-025-00395-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147288807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the theranostic potential of two metabolically stable GRPR-targeting peptides labelled with Ga-68 for PET imaging","authors":"Karim Obeid,&nbsp;Ekaterina Bezverkhniaia,&nbsp;Vladimir Tolmachev,&nbsp;Anna Orlova,&nbsp;Panagiotis Kanellopoulos","doi":"10.1186/s41181-026-00431-5","DOIUrl":"10.1186/s41181-026-00431-5","url":null,"abstract":"<div><h3>Background</h3><p>Gastrin-releasing peptide receptor (GRPR) attracts increasing attention as a target for radiotheranostic applications. We previously developed a metabolically stable GRPR-targeting peptide, incorporating α-methyl-L-tryptophan within its sequence (PEG₂-Pip-D-Phe⁶-Gln⁷-MetTrp⁸-Ala⁹-Val¹⁰-Sar¹¹-His¹²-Sta¹³-Leu¹⁴-NH₂) and coupled it to DOTAGA chelator (PKB2) and to DOTA (PKB3). When labelled with Lu-177, both peptide variants demonstrated promising properties for targeted radionuclide therapy.</p><h3>Results</h3><p>In this study, we aimed to evaluate the diagnostic counterparts of PKB2 and PKB3 by radiolabelling them with Ga-68 for positron emission tomography (PET) imaging. [⁶⁸Ga]Ga-PKB2 and [⁶⁸Ga]Ga-PKB3 were produced with radiochemical yields over 99% and radiochemical purities over 97%. Both radiopeptides showed a high GRPR affinity with IC₅₀ values in the low nanomolar range and a GRPR-mediated uptake in PC-3 cells with slow internalization. The labelled peptides [⁶⁸Ga]Ga-PKB2 and [⁶⁸Ga]Ga-PKB3 demonstrated fast clearance with activity concentration in blood below 0.5%IA/g at 2 pi, and a high tumour activity uptake in PC-3 xenografts (16 ± 3%IA/g and 17 ± 2%IA/g, respectively). [⁶⁸Ga]Ga-PKB3 had a significantly higher activity uptake in the pancreas (GRPR-expressing organ) and lower uptake in the kidneys than [⁶⁸Ga]Ga-PKB2. PET/CT images were concordant with the biodistribution results, clearly delineating tumour tissue.</p><h3>Conclusions</h3><p>[⁶⁸Ga]Ga-PKB2 and [⁶⁸Ga]Ga-PKB3 are promising PET tracers for imaging of GRPR-positive tumours and are potential diagnostic counterparts to their ¹⁷⁷Lu-labelled analogues, supporting their use as a ¹⁷⁷Lu/⁶⁸Ga theranostic pair.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12929764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146211865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increasing the activity output and optimization of automated radiosynthesis [68Ga]Ga-DOTATATE, [68Ga]Ga-Pentixafor, and [68Ga]Ga-FAPI-64 using two [68Ge]Ge/[68Ga]Ga iThemba generators in series","authors":"Ammar Alfteimi,&nbsp;Ulf Lützen,&nbsp;Alexander Helm,&nbsp;Michael Jüptner,&nbsp;Yi Zhao,&nbsp;Maaz Zuhayra","doi":"10.1186/s41181-026-00426-2","DOIUrl":"10.1186/s41181-026-00426-2","url":null,"abstract":"<div><h3>Background</h3><p>The rapidly increasing clinical demand for ⁶⁸Ga-labelled radiopharmaceuticals continues to challenge current production capacities, particularly in high-throughput nuclear medicine departments. Although dual-generator concepts have previously been explored, all reported approaches to date have required either pre-purification, fractionated elution, or additional cartridge-based concentration steps, which add complexity and limit routine clinical implementation. In the present study, we report for the first time a fully automated, GMP-compliant synthesis protocol using two iThemba ⁶⁸Ge/⁶⁸Ga generators connected in series on a standard EasyOne module applicable to three clinically relevant tracers. We successfully established robust GMP production of [⁶⁸Ga]Ga-DOTATATE, [⁶⁸Ga]Ga-FAPI-46, and [⁶⁸Ga]Ga-PentixaFor without any pre-purification or fractional elution. A key mechanistic finding of this work is the critical role of direct ascorbic acid addition to the reaction medium, which effectively suppresses radiolysis and metal-ion interference under high-activity conditions.</p><h3>Results</h3><p>We established a Good Manufacturing Practice (GMP)-compliant, fully automated synthesis of [⁶⁸Ga]Ga-DOTATATE, [⁶⁸Ga]Ga-Pentixafor, and [⁶⁸Ga]Ga-FAPI-46 using two ⁶⁸Ge/⁶⁸Ga iThemba generators connected in series, of which the older generator is replaced with a new one every 6 months. This configuration enabled elution of maximum activity of 3750 MBq and minimum activity of 2345 MBq, exceeding the elution activity achieved with a single generator by 2300 and 901 MBq respectively. The corrected yield of the labelled products was 91 ± 5% (72 ± 5% non-decay corrected). The additional activity of the labeled products obtained through the two generator configuration enables the examination of 2–4 additional patients per batch and thus resulting in significant cost savings. The direct addition of ascorbic acid to the reaction medium was essential, as it suppressed radiolysis and minimized the impact of metallic impurities. This innovation enabled reproducible labeling without pre-purification, which has not previously been demonstrated with SnO₂-based generators.</p><h3>Conclusions</h3><p>Dual-generator elution on the EasyOne module without modification of Trasis single-use cassettes provides a robust and scalable approach for high-yield production of ⁶⁸Ga radiopharmaceuticals. The integration of series-connected iThemba generators with in-situ radiolysis control by ascorbic acid ensures consistent GMP-compliant synthesis of [⁶⁸Ga]Ga-DOTATATE, [⁶⁸Ga]Ga-Pentixafor, and [⁶⁸Ga]Ga-FAPI-46. This method improves production efficiency, reduces costs, and expands clinical accessibility.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12929757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146211872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solving the limited availability of Astatine-211 from a European perspective: from production to the end user","authors":"Sture Lindegren,&nbsp;Holger Jensen,&nbsp;Hans Van de Maele,&nbsp;Renata Mikolajczak,&nbsp;Haingo Rabarijaona,&nbsp;Emma Aneheim","doi":"10.1186/s41181-026-00428-0","DOIUrl":"10.1186/s41181-026-00428-0","url":null,"abstract":"<div><h3>Background</h3><p>Astatine-211, ²¹¹At, has long been a candidate for Targeted Alpha Therapy, TAT. However, over time, hurdles in the development of chemistry, the establishment of radiopharmacies, and the demonstration of its potential in clinical trials have been hampered by its limited availability. It is one of the rarest elements on earth and must be produced artificially. The main production route is by irradiating natural bismuth with helium ions in a cyclotron, utilizing the nuclear reaction ²⁰⁹Bi(α,2n)²¹¹At. It requires a medium-energy cyclotron capable of producing a 29 MeV α-beam. Early on, there were several such cyclotrons in Europe and worldwide, but to this day, only a few have been producing ²¹¹At. Now, many of the old cyclotrons have been decommissioned, leaving even fewer options. However, the situation is about to change with the installation of several new cyclotrons with the capacity to produce a relevant α-beam. In addition, there are also prospects evaluating the production of ²¹¹At in linear particle accelerators, LINACs, with which ²¹¹At potentially can be produced in very high amounts and high activity levels. Taking advantage of LINAC machines and new and old cyclotrons still in operation can solve the limited access to ²¹¹At today. With the production capacity in place, the astatine produced must be delivered in a relevant form to the end user. For this purpose, it also needs to meet all regulations for transporting radioactive material. </p><h3>Main body</h3><p>This work is the result of European Cooperation in Science and Technology, COST Action CA 19114, Network for Optimized Astatine labeled Radiopharmaceuticals, NOAR, Work Group 1 assignments, focusing on all aspects on ²¹¹At production and availability. The review addresses the progress of ²¹¹At in terms of the requirement for its targetry, production, transport and the chemical and physical form for its delivery.</p><h3>Conclusion</h3><p>With all efforts in production and making ²¹¹At available it has the potential to be the next generation Targeted Alpha Therapy radionuclide in Europe and worldwide.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12929731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146211856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel 18F-labelled tetrazine ester prosthetic group for improved radiolabelling and in vivo stability of proteins and peptides","authors":"Francesco Lechi,&nbsp;Luke R. Odell,&nbsp;Olivia Wegrzyniak,&nbsp;Lorenzo J. I. Balestri,&nbsp;Olof Eriksson,&nbsp;Jonas Eriksson","doi":"10.1186/s41181-026-00430-6","DOIUrl":"10.1186/s41181-026-00430-6","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Monoclonal antibodies, engineered protein scaffolds, and peptides are increasingly important in therapy and diagnostics owing to their high specificity and affinity. Recent advances have enabled radiolabelling of such compounds with fluorine-18 in aqueous solution at room temperature via conjugation of [&lt;sup&gt;18&lt;/sup&gt;F]tetrazines with trans-cyclooctene (TCO) moieties through the inverse electron-demand Diels–Alder (IEDDA) reaction. To simplify fluorine-18 labelling of large molecules, a novel tetrazine: 4-(6-methyl-1,2,4,5-tetrazin-3-yl)benzyl 6-[fluoro-&lt;sup&gt;18&lt;/sup&gt;F]nicotinate ([&lt;sup&gt;18&lt;/sup&gt;F]TzE2), was here developed and synthesized in a single-step procedure directly on a standard QMA cartridge used for trapping [&lt;sup&gt;18&lt;/sup&gt;F]fluoride. The QMA containing [&lt;sup&gt;18&lt;/sup&gt;F]fluoride was eluted over 2 min with &lt;i&gt;N&lt;/i&gt;,&lt;i&gt;N&lt;/i&gt;,&lt;i&gt;N&lt;/i&gt;-trimethyl-5-(((4-(6-methyl-1,2,4,5-tetrazin-3-yl)benzyl)oxy)carbonyl)pyridin-2-aminium chloride in acetonitrile, forming [&lt;sup&gt;18&lt;/sup&gt;F]TzE2 instantaneously as it passed through the cartridge. [&lt;sup&gt;18&lt;/sup&gt;F]TzE2 was designed to combine the most favourable features of the previously described tetrazine prosthetic groups, [&lt;sup&gt;18&lt;/sup&gt;F]TzAm and [&lt;sup&gt;18&lt;/sup&gt;F]TzE, specifically, the superior in vivo performance and stability of [&lt;sup&gt;18&lt;/sup&gt;F]TzAm, and the efficient and practical radiosynthesis of [&lt;sup&gt;18&lt;/sup&gt;F]TzE. [&lt;sup&gt;18&lt;/sup&gt;F]TzE2 was evaluated biologically as a reagent for direct labelling of the TCO-conjugated Affibody molecule Z09591, a high affinity marker for PDGFRβ.&lt;/p&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The radiochemical yield for [&lt;sup&gt;1&lt;/sup&gt;⁸F]TzE2 was 30.4 ± 3% (n = 4), corresponding to an activity yield of 5.8 GBq starting from 20 GBq [&lt;sup&gt;1&lt;/sup&gt;⁸F]fluoride, with a total synthesis time of 13 min. [&lt;sup&gt;18&lt;/sup&gt;F]TzE2 demonstrated greater stability in human plasma than the previous ester tetrazine [&lt;sup&gt;18&lt;/sup&gt;F]TzE, but was significantly less stable than [&lt;sup&gt;18&lt;/sup&gt;F]TzAm. The Affibody molecule Z09591 was successfully radiolabelled, giving an activity yield of 410 ± 160 MBq and &gt; 90% radiochemical purity within a total synthesis time of 30 min from [&lt;sup&gt;18&lt;/sup&gt;F]fluoride. [&lt;sup&gt;18&lt;/sup&gt;F]TzE2-Z09591 exhibited improved plasma stability relative to [&lt;sup&gt;18&lt;/sup&gt;F]TzE-Z09591, though lower than [&lt;sup&gt;18&lt;/sup&gt;F]TzAm-Z09591. [&lt;sup&gt;18&lt;/sup&gt;F]TzE2-Z09591 retained specific blockable binding to PDGFRβ-expressing human and murine tissues as demonstrated by in vitro autoradiography. Biodistribution of [&lt;sup&gt;18&lt;/sup&gt;F]TzE2-Z09591 was rapid, with predominantly renal clearance, and showed improved targeting of PDGFRβ-expressing tissues compared with [&lt;sup&gt;18&lt;/sup&gt;F]TzE-Z09591.&lt;/p&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;The novel tetrazine prosthetic group [&lt;sup&gt;18&lt;/sup&gt;F]TzE2 enabled straightforward radiolabelling of Affibody molecule Z09591 without affecting its binding properties. [&lt;sup&gt;18&lt;/sup&gt;F]TzE2-Z09591 showed improved stability and in vivo targeting of PDGFRβ compared with the previously repo","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12929760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Balancing innovation and accessibility in infection imaging: lessons from the [99mTc]Tc-besilesomab paradox","authors":"Océane Mesnilgrante,&nbsp;Typhanie Ladrière,&nbsp;Noémie Allouche,&nbsp;Laura Aussage,&nbsp;Frédérique Grandhomme,&nbsp;Stéphane Allouche,&nbsp;Damien Peyronnet,&nbsp;Jonathan Vigne","doi":"10.1186/s41181-026-00427-1","DOIUrl":"10.1186/s41181-026-00427-1","url":null,"abstract":"<div><h3>Background</h3><p>Infection imaging plays a crucial role in clinical decision making, guiding antibiotic therapy and surgical management. Nuclear medicine offers molecular level approaches using three main techniques: [¹⁸F]FDG PET/CT, radiolabelled white blood cell (WBC) scintigraphy, and anti-granulocyte monoclonal antibody scintigraphy with [^99mTc]Tc-besilesomab. Among these, [^99mTc]Tc-besilesomab was developed to simplify infection imaging compared with in vitro WBC labelling, improving accessibility for hospitals without cell-labelling facilities. However, its use is restricted by the need for prior testing for human anti-mouse antibodies (HAMA) to prevent hypersensitivity reactions.</p><h3>Main body</h3><p>In recent years, significant regulatory changes in the European framework for in vitro diagnostics (IVDR 2017/746) have coincided with the withdrawal of the quantitative HAMA enzyme-linked immunosorbent assay from the market and its replacement with a qualitative rapid test. Although this shift aimed to streamline in vitro testing procedures, it has complicated the interpretation of HAMA results and raised concerns about diagnostic accessibility. In some centres, an increase in positive results has been observed with rapid tests, suggesting that patients may be inappropriately excluded from [^99mTc]Tc-besilesomab imaging. This situation highlights a paradox: a radiopharmaceutical designed to improve accessibility is now constrained by regulatory and methodological factors. The issue also reflects a broader challenge in nuclear medicine, ensuring patient safety and compliance without limiting access to essential diagnostic tools.</p><h3>Conclusion</h3><p>This debate argues that restoring accessibility to [^99mTc]Tc-besilesomab immunoscintigraphy requires both technological and regulatory innovation. Developing quantitative point-of-care HAMA assays, promoting humanised or nanobody-based tracers, and establishing harmonised European guidelines could help balance patient safety with diagnostic availability. The [^99mTc]Tc-besilesomab case exemplifies how well-intentioned regulatory transitions may have unintended consequences, underscoring the need for a pragmatic equilibrium between innovation, safety, and accessibility in infection imaging.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13000082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new 68Ga-labeled dimeric FAP ligand to advance targeted PET imaging of cancer","authors":"Feng Li,&nbsp;Chaitanya Kondam,&nbsp;Zhen Yang,&nbsp;Muthuraju Sangu,&nbsp;Jiexiao Chen,&nbsp;Rhonda Holgate,&nbsp;Bingqing Zou,&nbsp;Jiankang Jin,&nbsp;James Nguyen,&nbsp;Philip Martin,&nbsp;Shu Zhang,&nbsp;Yanping Yang,&nbsp;Junhua Mai,&nbsp;Lan Zhou,&nbsp;Diego R. Martin,&nbsp;Zhonglin Liu","doi":"10.1186/s41181-026-00424-4","DOIUrl":"10.1186/s41181-026-00424-4","url":null,"abstract":"<div><h3>Background</h3><p>Fibroblast activation protein (FAP) has emerged as a critical biomarker in the tumor microenvironment of various cancers. Radioligands targeting FAP have shown promise for cancer theranostics. To advance cancer imaging, we synthesized a dimeric radioligand based on a 4-quinolinoyl-glycyl-2-cyanopyrrolidine scaffold and conducted studies in cells and mouse tumor models to evaluate its target-binding affinity and PET imaging performance.</p><h3>Results</h3><p>OncoFAP, a commercially available FAP ligand, was conjugated via amide coupling with 1,4-butanediamine to generate a monomeric intermediate, hmFAP₁. A homodimeric molecule, hmFAP₂, was synthesized by tethering two hmFAP₁ moieties into a single construct. In enzymatic inhibition assays, both hmFAP₁ and hmFAP₂ demonstrated specific antagonist activity against FAP, with hmFAP₂ exhibiting a 14-fold increase in inhibitory potency compared to hmFAP₁. Cy5.5 fluorescent derivatives of hmFAP₁ and hmFAP₂ were generated for cell-binding assays in HeLa cells and xenografted tumors with positive FAP expression, revealing enhanced targeting efficacy of Cy5.5-hmFAP₂. The IC₅₀ values derived from cell-binding curves were 130 nM for hmFAP₁ and 8 nM for hmFAP₂ (<i>P</i> &lt; 0.001). Using DOTA as the chelator, both ligands were radiolabeled with ⁶⁸Ga, yielding stable products [⁶⁸Ga]Ga-DOTA-hmFAP₁ and [⁶⁸Ga]Ga-DOTA-hmFAP₂ for PET imaging. Consistently, [⁶⁸Ga]Ga-DOTA-hmFAP₂ demonstrated superior tumor uptake with high specificity in mice bearing HeLa, MDA-MB-231, and HEK293T xenografts with variable levels of FAP expression. The liver and intestinal radioactivity showed no difference between the groups of mice imaged with [⁶⁸Ga]Ga-DOTA-hmFAP₂ and [⁶⁸Ga]Ga-DOTA-hmFAP₁.</p><h3>Conclusions</h3><p>hmFAP₂ markedly enhances FAP-targeting efficiency, providing higher binding affinity, improved tumor uptake, and reduced nonspecific distribution compared with its monomeric counterpart. The favorable imaging properties of hmFAP₂ position it as a promising candidate for translation into clinical PET imaging and as a potential scaffold for developing FAP-targeted theranostic agents.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and preclinical development of a novel 68Ga/89Zr-Labelled ανβ6-integrin targeting trimer","authors":"Giacomo Gariglio,&nbsp;Fernando A Patiño Álvarez,&nbsp;Maximilian A Zierke,&nbsp;Stefan Stangl,&nbsp;Tim Rheinfrank,&nbsp;Nadine Holzleitner,&nbsp;Susanne Kossatz,&nbsp;Clemens Decristoforo","doi":"10.1186/s41181-025-00423-x","DOIUrl":"10.1186/s41181-025-00423-x","url":null,"abstract":"<div><h3>Background</h3><p>The αvβ6 integrin has emerged as a valuable target for theranostic applications in nuclear medicine with high applicability across a variety of cancers, including head-and-neck, lung, breast, and pancreatic carcinomas. [⁶⁸Ga]Ga-Trivehexin is a prominent example of a diagnostic tracer targeting this integrin. In this work, we aimed to expand on this concept by developing FSC(PEG4-αvβ6)₃, a novel tracer that retains the Trivehexin design, but features PEGylated spacers and replaces the TRAP chelator with Fusarinine C (FSC), enabling labelling with Zirconium-89 in addition to Gallium-68. Preclinical characterization of [⁶⁸Ga]Ga/[⁸⁹Zr]Zr-FSC(PEG4-αvβ6)₃ included affinity determination towards the αvβ6 integrin and cellular uptake studies in αvβ6-positive H2009 cells. A subcutaneously xenografted H2009 tumor model was used to assess the PET imaging potential and biodistribution at early time points with the Gallium-68 labelled compound, and at later time points (up to 6 days post-injection) with the Zirconium-89 labelled version.</p><h3>Results</h3><p>While [⁶⁸Ga]Ga-FSC(PEG4-αvβ6)₃ exhibited moderate binding to αvβ6, its affinity, cellular internalization, and tumor uptake <i>in vivo</i> were lower compared to [⁶⁸Ga]Ga-Trivehexin. Notably, this decreased target engagement was associated with reduced nonspecific binding, which we primarily attributed to the incorporation of PEGylated linkers. Despite indication of <i>in vivo</i> degradation of [⁸⁹Zr]Zr-FSC(PEG4-αvβ6)₃, still a meaningful evaluation of pharmacokinetics and biodistribution at extended time points was feasible, revealing prolonged tumor persistence up to 6 days post-injection.</p><h3>Conclusions</h3><p>FSC(PEG4-αvβ6)₃ represents the first-generation tracer targeting the αvβ6 integrin based on the multifunctional chelator Fusarinine C, thereby expanding the repertoire of radionuclides applicable from Gallium-68 to Zirconium-89. Following further optimization, this novel class of compounds holds significant promise for enabling clinical translation and advancing the development of next-generation αvβ6-directed imaging agents.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12932792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparative assessment of radiochemical purity and yield of [18F]PSMA-1007 production using two different automated synthesis platforms: a head-to-head comparison","authors":"Michela Cossandi,&nbsp;Massimo Statuto,&nbsp;Elena Migliorati,&nbsp;Gian Luca Viganò,&nbsp;Luigi Spiazzi,&nbsp;Carlo Rodella,&nbsp;Pietro Bellini,&nbsp;Roberto Rinaldi,&nbsp;Luca Camoni,&nbsp;Francesco Dondi,&nbsp;Giorgio Biasiotto,&nbsp;Francesco Bertagna","doi":"10.1186/s41181-026-00425-3","DOIUrl":"10.1186/s41181-026-00425-3","url":null,"abstract":"<div><h3>Background</h3><p>Glutamate carboxypeptidase II (GCPII), also known as prostate-specific membrane antigen (PSMA) is overexpressed in 90–100% of prostate cancer cells. The radiopharmaceutical [¹⁸F]PSMA-1007, recognised as a PET tracer for prostate cancer imaging, is based on PSMA inhibitor [Glu-CO-Lys(2Nal-Amb-Glu-Glu-PyTMA)] bound to the radioisotope Fluorine-18. [¹⁸F]Fluoride was obtained via the ¹⁸O(p,n)¹⁸F reaction using a cyclotron for medical use, while synthesis of [¹⁸F]PSMA-1007 was performed with two different platforms: FASTlab2 and NEPTIS^® Perform. Both modules enabled synthesis through nucleophilic substitution reaction and subsequent purification in solid phase extraction (SPE). Quality control process was validated according to the current specific monograph (3116) of the European Pharmacopoeia (Ph. Eur.) before clinical use.</p><h3>Results</h3><p>Twenty syntheses of [¹⁸F]PSMA-1007 for each module were performed in order to evaluate and compare radiochemical purity (96.58% ± 1.25 with FASTlab2 vs 95.86% ± 0.79 with NEPTIS^® Perform) and decay-corrected radiochemical yield (43.7% ± 3 with FASTlab2 vs 28.5% ± 3.1 with NEPTIS^® Perform).</p><h3>Conclusion</h3><p>Both platforms produced [¹⁸F]PSMA-1007 that consistently met all pharmacopoeial quality control standards. However, the FASTlab2 system demonstrated a statistically significant higher decay-corrected radiochemical yield (43.7% ± 3% vs. 28.5% ± 3.1%, <i>p</i>-value &lt; 0.001 after statistical testing). While this yield difference does not impact radiochemical purity or product safety, it may represent a relevant advantage in terms of production efficiency and available activity for clinical use, which may influence the choice of synthesizer.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12913835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality control of actinium-225 and 225Ac-radiopharmaceuticals: Francium-221 to be or not to be?","authors":"Miguel Toro-Gonzalez,&nbsp;Luke Wheeless,&nbsp;Vijai Kumar Reddy Tangadanchu,&nbsp;Cory Hawkins,&nbsp;Shannon Provo,&nbsp;William Smith,&nbsp;Michael Hommen,&nbsp;Dan DeVries,&nbsp;Jim Harvey,&nbsp;Tyler Drum,&nbsp;Diane S. Abou","doi":"10.1186/s41181-025-00419-7","DOIUrl":"10.1186/s41181-025-00419-7","url":null,"abstract":"<div><h3>Background</h3><p>Actinium-225 radiopharmaceuticals have drawn great interest in cancer therapy due to their tumor-specific delivery of cytotoxic alpha-particles. Quality control (QC) is critical for these potent agents and there is currently no consensus for best practice of actinium-225 QC. Detection of actinium-225 (T_1/2 = 9.92 days) is challenging; however, the francium-221 (T_1/2 = 4.8 min, 218 keV) and bismuth-213 (T_1/2 = 45 min, 440 keV) gamma-emitting progenies facilitate the quantification. Multiple analytical methods were investigated for limit of quantification (LOQ), radiochemical yield (RCY%), and radiochemical purity (RCP%). Those were evaluated at both francium-221 and bismuth-213 secular equilibria, and compared for accuracy and precision. While each secular equilibrium has been amply explored for actinium-225 quantification, a direct comparison between the two approaches has sparsely been examined. The RCY% was evaluated using two TLC plate readers: a gas-filled proportional counter and a plastic silicon photomultiplier detector. TLC strips were also analyzed using Liquid Scintillation Counting (LSC), High Purity Germanium (HPGe), and NaI(Tl) gamma well counting. In absence of detectable radio-impurity, HPLC RCP% were correlated to RCY%. Finally, free actinium-225 spiking recoveries were evaluated in ²²⁵Ac-radiopharmaceuticals.</p><h3>Results</h3><p>The plastic silicon scanner resulted in RCY% differences between 30 min and &gt; 5 h evaluations, whereas the gas-filled proportional counter, when varying voltages, showed minor differences. Similarly, HPGe-TLC demonstrated equivalent RCY% between both equilibria. The NaI(Tl), LSC- TLC, and HPLC-gamma counting significantly underestimated RCY% or RCP% at 30 min. Considering gamma well counting LOQ and ²²⁵Ac-radiopharmaceutical low radioactive concentration, as low as 1% of free actinium-225 may be accurately detected in HPLC fractions. For TLC, LOQs were reported lower than measured in solution, free actinium-225 radioimpurity may be precisely measured as low as 0.5% of total content, except for the silicon detector.</p><h3>Conclusion</h3><p>Five instruments have been tested for their linearity, sensitivity, accuracy and specificity to actinium-225 quantification using francium-221 and bismuth-213 equilibria. Francium-221 equilibrium was deemed acceptable for TLC RCY% using HPGe and gas-filled proportional counter. Gamma well counting, LSC, and plastic silicon detector required bismuth-213 equilibrium for accurate RCY%. Low content free actinium-225 impurity was accurately reported for all methods except for the silicon detector. Overall, this investigation sheds light on the appropriate analytical methods for ²²⁵Ac-radiopharmaceutical QC considering secular equilibrium.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-025-00419-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}