EJNMMI Radiopharmacy and Chemistry最新文献

{"title":"Highlight selection of radiochemistry and radiopharmacy developments by editorial board","authors":"Sarah Spreckelmeyer,&nbsp;Jean DaSilva,&nbsp;Clemens Decristoforo,&nbsp;Robert H. Mach,&nbsp;Jan Passchier,&nbsp;Giuseppe Carlucci,&nbsp;Adriano Duatti,&nbsp;Bart T. Cornelissen,&nbsp;Antonia Denkova,&nbsp;Jeroen Hendrikx,&nbsp;Yann Seimbille,&nbsp;Xing Yang,&nbsp;Hongmei Jia,&nbsp;Ming-Rong Zhang,&nbsp;Lars Perk,&nbsp;Peter Caravan,&nbsp;Jan Rijn Zeevaart,&nbsp;Julien Leenhardt,&nbsp;Juan Pellico,&nbsp;Mohammed Hussain Al-Qahtani,&nbsp;Zhen Cheng,&nbsp;Tamer Sakr,&nbsp;Min Yang","doi":"10.1186/s41181-026-00505-4","DOIUrl":"10.1186/s41181-026-00505-4","url":null,"abstract":"<div><h3>Background</h3><p>The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development and application of radiopharmaceuticals.</p><h3>Main Body</h3><p>This selection of highlights provides commentary on 23 different topics selected by each co-authoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry, proof-of-concepts, preclinical and early clinical studies using novel radiopharmaceuticals.</p><h3>Conclusion</h3><p>Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field in many aspects.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00505-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149132687","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":"Methods for assessing binding of a small-molecule radioligand to soluble enzyme isocitrate dehydrogenase 1 variants","authors":"Winnie Deuther-Conrad,&nbsp;Thu Hang Lai,&nbsp;Andreas Maurer,&nbsp;Barbara Wenzel","doi":"10.1186/s41181-026-00502-7","DOIUrl":"10.1186/s41181-026-00502-7","url":null,"abstract":"<div><h3>Background</h3><p>Isocitrate dehydrogenase 1 (IDH1) is a cytosolic NADP⁺-dependent enzyme involved in cellular redox homeostasis and 2-oxoglutarate (2-OG) metabolism. Glioma-associated mutations in IDH1 confer a neomorphic enzymatic activity, resulting in the production and accumulation of the oncometabolite D-2-hydroxyglutarate (2-HG), which contributes to metabolic and epigenetic alterations in IDH-mutant tumors. Small-molecule inhibitors of mutant IDH1 have emerged as promising therapeutic agents. In parallel, radiolabeled derivatives of these inhibitors are being investigated as potential positron emission tomography (PET) tracers for non-invasive imaging of mutant IDH1. Characterizing the binding of small-molecule radioligands to soluble intracellular proteins such as IDH1, however, presents specific methodological challenges. Appropriate experimental approaches are therefore needed to characterize radioligand binding to IDH1 enzymes.</p><h3>Results</h3><p>Using several established biochemical and biophysical approaches, we found that the radiofluorinated inhibitor ivosidenib ([¹⁸F]AG-120) binds specifically to both IDH1 and IDH1^R132H at nanomolar radioligand concentrations. However, the investigated approaches yielded method-dependent apparent affinity estimates.</p><h3>Conclusions</h3><p>The findings support the use of radioligand-based approaches for characterizing soluble intracellular protein targets, while highlighting the need for assay-specific optimization and careful interpretation of quantitative binding parameters.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00502-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023582","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":"Optimization, automation and validation of NOP receptor PET radiopharmaceutical, [11C]NOP-1A for human use","authors":"Daniel L. Yokell,&nbsp;Maeva Dhaynaut,&nbsp;Ramesh Neelamegam,&nbsp;Peter A. Rice,&nbsp;Jacqueline Noel,&nbsp;Marc D. Normandin,&nbsp;Diego A. Pizzagalli,&nbsp;Georges El Fakhri","doi":"10.1186/s41181-026-00479-3","DOIUrl":"10.1186/s41181-026-00479-3","url":null,"abstract":"<div><h3>Background</h3><p>In vivo human studies of the nociceptin/orphanin FQ peptide (NOP) receptor have been limited by the availability and reliable production of suitable PET radioligands. [¹¹C]NOP-1A is a high-affinity PET radioligand for imaging NOP receptors; however, reproducible production suitable for routine clinical use has been challenging. The aim of this study was to optimize, automate, and validate the radiosynthesis of [¹¹C]NOP-1A for cGMP-compliant human PET imaging.</p><h3>Results</h3><p>We developed a fully automated loop radiomethylation method for the production of [¹¹C]NOP-1A using the commercially available GE TRACERlab™ FXC Pro synthesis module and validated the process according to United States Food and Drug Administration (FDA) and United States Pharmacopeia (USP) requirements. Multiple radiolabeling conditions were evaluated using different bases and solvents. Optimal production was achieved using [¹¹C]CH₃I in the presence of sodium hydride (NaH) and dimethylformamide (DMF), resulting in reliable and reproducible synthesis with radiochemical conversion of up to 60%. Validation studies demonstrated successful production of [¹¹C]NOP-1A with radiochemical purity ranging from 97.5 to 99.6%, molar activity of 79.4–162.9 GBq/μmol at end of synthesis, and a corrected radiochemical yield of 13 ± 2.5% relative to starting [¹¹C]CO₂. All quality control parameters met predefined acceptance criteria for human administration.</p><h3>Conclusions</h3><p>A robust, fully automated, and cGMP-compliant production method for [¹¹C]NOP-1A was successfully developed and validated for human use. This approach provides reliable routine production of [¹¹C]NOP-1A and facilitates broader clinical and translational investigation of the NOP receptor system in neuropsychiatric and neurological disorders.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00479-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981770","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":"The influence of functional groups and their relative position on isotopic exchange between 19F and 18F in aromatic rings","authors":"Antonia A. Högnäsbacka,&nbsp;Miguel A. Cortés González,&nbsp;Afrizki D. Wiranegara,&nbsp;Magnus Schou","doi":"10.1186/s41181-026-00494-4","DOIUrl":"10.1186/s41181-026-00494-4","url":null,"abstract":"<div><h3>Background</h3><p>Isotopic exchange with fluorine-18 offers a conceptually simple approach to positron emission tomography (PET) tracer development, as the target compound itself serves as the labeling precursor.</p><h3>Results</h3><p>In this study, we investigated the influence of functional groups and substituent position on the efficiency of isotopic exchange with fluorine-18. A total of 19 fluorobenzene derivatives were screened under standardized conditions, in dimethyl sulfoxide (175 °C) and dimethylformamide (150 °C) as solvents. Only a subset of compounds underwent efficient exchange; electron-withdrawing substituents strongly promoted isotopic exchange, with ortho and para isomers generally being more reactive than meta-analogues. The kinetics of the exchange in dimethyl sulfoxide were quantified for fluorobenzonitriles, nitrofluorobenzenes, and fluorobenzaldehydes. Nonlinear regression analysis indicated more rapid apparent exchange for the ortho- and para-substituted nitrile and nitro derivatives, together with higher apparent plateaus (≥84–94%), consistent with an S_NAr-like mechanism involving stabilization of the Meisenheimer intermediate. By contrast, meta isomers were significantly less reactive, and no exchange was detected for 3-fluorobenzaldehyde. Fluorobenzaldehydes also showed lower overall apparent plateaus and signs of thermal instability in dimethyl sulfoxide. Full-scale labeling confirmed the feasibility of high molar activity, with isolated 2-[¹⁸F]fluorobenzonitrile obtained at 121 ± 37 GBq/µmol. Although radiochemical yield (5.84±2.23%, decay-corrected to the addition of tetraethylammonium [¹⁸F]fluoride) and radiochemical purity (88.6 ± 3.9%) remained modest, these results demonstrate that isotopic exchange can provide molar activities within the range required for PET radiopharmaceuticals.</p><h3>Conclusions</h3><p>These findings clarify the functional group and positional influences on fluorine-19/fluorine-18 isotopic exchange, highlighting the potential of this strategy to streamline PET tracer development by circumventing the need for precursor development and extensive reaction optimization.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863326","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":"Development and preclinical evaluation of selective vinyl sulfone-based probes for PET imaging of tumor-associated cathepsins","authors":"Oliviero Cini,&nbsp;Alan Miranda,&nbsp;Daan Willocx,&nbsp;Angeliki Karakasidi,&nbsp;Anke de Groot,&nbsp;Thales do Valle Moreira,&nbsp;Ana P. Leandro,&nbsp;Maria M. M. Santos,&nbsp;Rui Moreira,&nbsp;Filipe Elvas","doi":"10.1186/s41181-026-00493-5","DOIUrl":"10.1186/s41181-026-00493-5","url":null,"abstract":"<div><h3>Background</h3><p>Cysteine cathepsin L (CatL) is emerging as a key biomarker of cancer progression, making it an attractive candidate for non-invasive molecular imaging. To monitor enzymatic activity directly, rather than merely protein expression, activity-based probes (ABPs) enable selective targeting of enzymes through covalent binding at their active sites. Despite vinyl sulfones are well-established irreversible inhibitors of cathepsins, their application as positron emission tomography (PET) ABPs remains unexplored. In this study we describe the design, synthesis, and evaluation of a novel class of ⁶⁸Ga-labeled vinyl sulfone-based ABPs targeting CatL.</p><h3>Results</h3><p>A series of ABPs were synthesized based on the established vinyl sulfone scaffold K11777 (K777). Structure-activity relationship (SAR) analysis revealed that retaining a homophenylalanine (hPhe) residue at the P1 position resulted in greater CatL potency compared to its corresponding leucine (Leu) analogue. Evaluation of different linkers at the P3 position further revealed that polyethylene glycol (PEG) linkers preserved high CatL selectivity, whereas a piperazine linker increased off-target binding to cathepsin B (CatB). Based on these findings, two representative radiotracers were selected for further biological evaluation: the PEG2-linked [⁶⁸Ga]CREANT-101 and the piperazine-linked [⁶⁸Ga]CREANT-102. In vivo pharmacokinetic studies in healthy mice demonstrated that [⁶⁸Ga]CREANT-102 exhibited prolonged blood circulation and high non-specific tissue uptake, whereas [⁶⁸Ga]CREANT-101 displayed rapid systemic clearance and low background signal, supporting its selection for tumor imaging. In both U-87 MG and HT-29 xenograft models, [⁶⁸Ga]CREANT-101 showed modest absolute tumor uptake in vivo. However, subsequent ex vivo analysis of tumor homogenates confirmed successful and specific engagement of active cathepsins within the target tissue.</p><h3>Conclusions</h3><p>A novel class of ⁶⁸Ga-labeled vinyl sulfone ABPs targeting CatL was successfully developed and preclinically evaluated. The lead tracer, [⁶⁸Ga]CREANT-101, demonstrated high selectivity and a favorable background profile, but showed limited tumor accumulation in vivo. Ex vivo findings indicated that this limited tumor uptake was not attributable to insufficient target affinity, but rather to suboptimal cellular internalization and restricted tumor bioavailability, likely resulting from rapid systemic clearance and in vivo metabolic instability. Therefore, future optimization of this tracer class should focus on improving these pharmacokinetic properties to enhance in vivo tumor targeting.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904816","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":"Correction: Quality and pratical determinants in [99mTc]Tc-tetrofosmin preparation: hygrometry, syringe sorption & maximal activity per kit","authors":"Quentin Buon,&nbsp;Hugo Tep,&nbsp;Eli Bassi,&nbsp;Alessio Imperiale,&nbsp;Anne Dory,&nbsp;Bénédicte Gourieux,&nbsp;Alice Ressault","doi":"10.1186/s41181-026-00489-1","DOIUrl":"10.1186/s41181-026-00489-1","url":null,"abstract":"","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00489-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783227","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":"Radiosynthesis and preclinical evaluation of [11C]Methyl-V-0219, a small molecule glucagon-like peptide-1 allosteric modulator for PET brain imaging","authors":"Francesco Lechi,&nbsp;Amina Khalil,&nbsp;Pablo Novales Bautista,&nbsp;Jakob Öberg,&nbsp;Lorenzo Jacopo Ilic Balestri,&nbsp;Olof Eriksson,&nbsp;Jonas Eriksson,&nbsp;Luke R. Odell","doi":"10.1186/s41181-026-00486-4","DOIUrl":"10.1186/s41181-026-00486-4","url":null,"abstract":"<div><h3>Background</h3><p>Glucagon-like peptide-1 receptor (GLP-1R) is a clinically validated therapeutic target for the treatment of obesity and type 2 diabetes. GLP-1Rs expressed in the central nervous system (CNS) regulate appetite and are therefore particularly important in the context of weight loss. There is thus an emerging need for efficient and brain-penetrating Positron Emission Tomography (PET) technologies to study the distribution of GLP-1R in the CNS and facilitate the development of novel GLP-1R-targeted therapeutics. However, currently established GLP-1R PET tracers are peptide-based and exhibit limited blood–brain barrier (BBB) penetration, restricting their use for imaging central GLP-1R expression. V-0219, a small molecule GLP-1R positive allosteric modulator, represents a potential scaffold for the development of BBB-penetrating PET tracers targeting incretin receptor systems in the brain.</p><h3>Results</h3><p>Here, we report the radiosynthesis and preclinical evaluation of [¹¹C]Methyl-V-0219, a carbon-11 labelled analogue of V-0219. [¹¹C]Methyl-V-0219 was synthesized using a Pd(0)-mediated Suzuki–Miyaura coupling reaction and obtained with a radiochemical yield of 36 ± 18% (n = 16) and radiochemical purity of 98.6 ± 1.6% (n = 16). In vitro autoradiography demonstrated retained binding to GLP-1R–positive tissues, although binding to glucose-dependent insulinotropic polypeptide (GIP) and glucagon (GCG) receptors was also observed.</p><p>In vivo PET imaging was performed in rats and pigs and compared with the well-established GLP-1R tracer [⁶⁸Ga]Ga-DO3A-Exendin-4. Dynamic PET imaging demonstrated rapid brain uptake of [¹¹C]Methyl-V-0219 followed by progressive washout, indicating BBB penetration but limited retention in the brain. In contrast to [⁶⁸Ga]Ga-DO3A-Exendin-4, [¹¹C]Methyl-V-0219 did not demonstrate detectable retention in GLP-1R–rich tissues, including the pituitary gland and pancreas. Instead, prominent uptake was observed in the liver, intestines, and glandular tissues, consistent with hepatobiliary clearance and nonspecific accumulation of a lipophilic compound. Furthermore, blocking and competition studies did not alter tracer brain kinetics, suggesting no detectable displaceable binding in vivo.</p><h3>Conclusion</h3><p>Taken together, these findings demonstrate the feasibility of developing small–molecule–based PET tracers targeting incretin receptor systems, while highlighting the challenges associated with achieving sufficient in vivo specificity for brain GLP-1R imaging.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00486-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148782001","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":"Stable core-encapsulation of indium-111 in crosslinked polyionic complex micelles and assessment of its biodistribution","authors":"Hayato Laurence Mizuno,&nbsp;Sotaro Miyao,&nbsp;Hiroyuki Takahashi,&nbsp;Nobuyoshi Akimitsu,&nbsp;Yasutaka Anraku","doi":"10.1186/s41181-026-00478-4","DOIUrl":"10.1186/s41181-026-00478-4","url":null,"abstract":"<div><h3>Background</h3><p>Radioactive isotopes, such as Indium-111 (¹¹¹In), are pivotal for highly sensitive noninvasive imaging and targeted radiotherapy. However, achieving stable in vivo retention remains a critical barrier. Conventional nanocarriers typically rely on surface-bound chelators, exposing the isotopes to biological transchelation and detachment, while potentially altering the carrier’s surface properties and pharmacokinetics. To address these limitations, this study evaluates a polyionic complex micelle (PICm) platform designed to encapsulate ¹¹¹In within a crosslinked core using DOTA chelation. This approach aims to enhance radiochemical stability while preserving the micelle’s native, engineered surface characteristics.</p><h3>Results</h3><p>DOTA-functionalized PICm were fabricated through electrostatic self-assembly of PEG-based polymers and subsequent core crosslinking. The resulting micelles exhibited a highly uniform size (32.6 ± 6.3 nm) and a modestly negative surface charge (− 4.9 ± 1.0 mV). Stability assays demonstrated that under the acidic conditions required for ¹¹¹In chelation (pH 5.5), the micelles undergo reversible size swelling driven by polymer protonation without aggregating or collapsing, confirming that core crosslinking successfully maintains micellar integrity. In vivo biodistribution in CT26 tumor-bearing mice revealed that ¹¹¹In-loaded PICm displayed prolonged systemic presence, with tumor accumulation peaking at 2.3 ± 0.4%ID/g at 24 h post-injection via the enhanced permeability and retention effect. Hepatic and splenic uptakes aligned with typical nanoparticle clearance pathways.</p><h3>Conclusions</h3><p>The core-loading of PICm may offer advantages over surface-chelated nanocarriers. By maintaining structural integrity during radiolabeling and extending systemic circulation in vivo, these results validate the platform’s robustness and passive tumor accumulation, highlighting its potential as a versatile vehicle for the delivery of diagnostic radionuclides.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13438075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668042","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":"High-yield reactor production of terbium-161 using thin-layer gadolinium-160 targets, simplified chloride based separation and radiolabeling of DOTA based ligands","authors":"Shakera Khatoon,&nbsp;Amna Javed,&nbsp;Qaiser Khan,&nbsp;Kaleem Abbas","doi":"10.1186/s41181-026-00474-8","DOIUrl":"10.1186/s41181-026-00474-8","url":null,"abstract":"<div><h3>Background</h3><p>Terbium-161 (¹⁶¹ Tb) is an emerging therapeutic radionuclide combining β⁻ emission with a high yield of Auger electrons and conversion electrons, enabling enhanced localized dose deposition. However, its widespread clinical adoption is limited by inefficient target utilization and multistep post-irradiation processing. This study aimed to develop a simplified high-yield production and direct chloride-based purification workflow for clinical-grade terbium-161 using thin-layer enriched gadolinium-160 targets under limited-resource reactor conditions. Terbium-161 was produced by neutron irradiation of enriched Gadolinium-160 targets fabricated as conventional oxide powder and novel thin-layer chloride films at a thermal neutron flux of 1.5 × 10¹⁴ n cm⁻² s⁻¹ for 24 h in Pakistan Atomic Research Reactor-1 (PARR-I). Post-irradiation separation of terbium was carried out using LN resin employing HCl and HNO₃ media, and compared with α-hydroxyisobutyric acid (α-HIBA) cation-exchange chromatography. Radionuclidic purity was assessed by HPGe γ spectrometry, while radiochemical purity and labeling efficiency with DOTA conjugated Peptides were evaluated using ITLC and HPLC.</p><h3>Results</h3><p>Thin-layer targets significantly enhanced neutron utilization, compared to oxide targets due to reduced self-shielding of target. The specific activities achieved across three production batches (34.25–79.01 MBq/mg) demonstrated an approximately 2.3-fold higher specific activity with ¹⁶⁰GdCl₃ layered targets than bulk Gd₂O₃ targets. LN–HCl separation provided superior recovery (91.4%) and enabled direct formulation of [¹⁶¹ Tb]TbCl₃, eliminating post-processing steps required in nitrate systems and cation exchange with α -HIBA. Radionuclidic purity exceeded 99.99%, with minimal Terbium-160 impurity and Radiolabeling yields with DOTA-conjugated peptides exceeded 95.0%.</p><h3>Conclusion</h3><p>Target geometry plays a critical role in reactor-based radionuclide production. The integrated thin-layer target and chloride-based separation workflow provides a simplified, high-yield approach for production of terbium-161, enables efficient radiolabeling with DOTA-based ligands. These findings provide a foundation for further analytical qualification required for preclinical and clinical translations.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073072","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":"High molar activity [¹¹C]phosgene from [¹¹C]CO₂.","authors":"Edla Kerminen, Thomas Keller, Simo Salo, Johan Rajander, Olof Solin, Anna Krzyczmonik, Anna K Kirjavainen","doi":"10.1186/s41181-026-00472-w","DOIUrl":"https://doi.org/10.1186/s41181-026-00472-w","url":null,"abstract":"<p><strong>Background: </strong>[¹¹C]Phosgene is a known but underutilised labelling synthon in PET-tracer development. The production of [¹¹C]phosgene faces many problems such as difficulties in achieving high molar activity, regular key component replacement and complexity of the synthesis, thereby hindering its wider use. In this paper, a robust and semi-automated synthesis route for production of [¹¹C]phosgene from [¹¹C]CO₂ was developed to solve issues restricting the use of [¹¹C]phosgene. The high molar activity [¹¹C]phosgene was then used for the labelling of biologically important molecules as a proof of concept.</p><p><strong>Results: </strong>[¹¹C]Phosgene was synthesized from [¹¹C]CO by UV-mediated photochemical chlorination with chlorine gas. [¹¹C]CO was produced by the fluoride-activated disilane reduction of cyclotron-produced [¹¹C]CO₂. [¹¹C]Phosgene was produced with satisfactory radiochemical yield (13 ± 1 GBq at EOS, 30 ± 4% dc. to SOS) based on [¹¹C]CO₂ and molar activity of 249 ± 40 GBq/µmol at EOS (n = 3). The radiosynthesis time was approximately 20 min.</p><p><strong>Conclusion: </strong>A robust synthesis route for production of high molar activity [¹¹C]phosgene from [¹¹C]CO₂ was developed. The simplicity and mild reaction conditions of the [¹¹C]CO production method used eliminate the previous issues with Zn-based reduction of [¹¹C]CO₂. Intermediate purification of [¹¹C]CO guaranteed efficient [¹¹C]phosgene production, and removal of unreacted Cl₂ minimised unwanted side reactions. This method utilises a fixed-line device with simple set up and mild conditions. With this method, it is possible to perform syntheses reliably with good radiochemical yields and high molar activities in a short synthesis time.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}