EJNMMI Radiopharmacy and Chemistry最新文献

{"title":"Potentials and practical challenges of terbium-161 labeled radiopharmaceuticals","authors":"Carolline M. Ntihabose,&nbsp;Maryana Handula,&nbsp;Amber Piet,&nbsp;Savanne Beekman,&nbsp;Louise van Dalen,&nbsp;Negin Eskandari,&nbsp;Asude Aydogan,&nbsp;Debra Stuurman,&nbsp;Corrina de Ridder,&nbsp;Mark Konijnenberg,&nbsp;Yann Seimbille,&nbsp;Erik de Blois","doi":"10.1186/s41181-025-00390-3","DOIUrl":"10.1186/s41181-025-00390-3","url":null,"abstract":"<div><h3>Background</h3><p>Due to promising preclinical studies and clinical case reports, Tb-161 labeled radiopharmaceuticals for targeted radionuclide therapy (TRT) have gained interest. Unlike Lu-177, Tb-161 not only emits β⁻ particles, but also Auger and conversion electrons, which may improve the current therapeutic efficacy of TRT. However, before implementing Tb-161 for clinical use, several steps are required (E.g., development, optimization, validation). Therefore, this study focuses on the purity of Tb-161 as well as the detection and quantification of Tb–Tb-161-labeled radiopharmaceuticals. As multiple studies are currently aiming to determine the therapeutic effect of Tb-161 labeled radiopharmaceuticals, standardizing and evaluating Tb-161 is essential to be able to compare its therapeutic potential against Lu-177 and other radionuclides. Therefore, we established accurate detection methods, impurity measurements, radiolabeling protocols, and quality control for Tb-161 labeled pharmaceuticals. Parameters of Tb-161 labeled radiopharmaceuticals were investigated and exemplified by [¹⁶¹ Tb]Tb-DOTA-TATE, in comparison with [¹⁷⁷Lu]Lu-DOTA-TATE.</p><h3>Results</h3><p>Analysis of Tb-161 stock solution demonstrated the presence of metal impurities (ΣFe, Zn, Cu, Gd, and Dy) at the reference day and increased over time. The geometric effect of vial type demonstrated a decrease in activity when a vial was used without point-source. For both Lu-177 and Tb-161 labeled DOTA-TATE, high radiochemical yield and purity (&gt; 95%) were obtained and remained stable (&gt; 90%) up to 24 h in solution.</p><h3>Conclusion</h3><p>Analysis of Tb-161 stock showed an increase in metal impurities over time, which could interfere with the production of Tb-161 labeled radiopharmaceuticals. The low gamma energy (48.9 keV and 74.6 keV) of Tb-161 needs to be considered in (pre)clinical applications when quantifying activity. For Tb-161 labeled pharmaceuticals, similar radiolabeling conditions as Lu-177 have been shown to be successful and highly stable.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00390-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210884","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":"Highlight selection of radiochemistry and radiopharmacy developments by editorial board","authors":"Jun Toyohara,&nbsp;Philipp H. Elsinga,&nbsp;Sergio Todde,&nbsp;Xiang-Guo Li,&nbsp;Silvio Aime,&nbsp;Wictor C. Szymanski,&nbsp;Nick van der Meulen,&nbsp;Frederik Cleeren,&nbsp;Ralf Schirrmacher,&nbsp;Hua Yang,&nbsp;Eduardo Savio,&nbsp;Naoual Bentaleb,&nbsp;Marcela Zubillaga,&nbsp;Ivis F. Chaple Gore,&nbsp;Mickaël Bourgeois,&nbsp;Archana Mukherjee,&nbsp;Juan Pellico,&nbsp;Klaus Kopka","doi":"10.1186/s41181-025-00387-y","DOIUrl":"10.1186/s41181-025-00387-y","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 18 different topics selected by each co-authoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of 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":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00387-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210882","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":"[11C]HSP990 PET as a translational tool to investigate the role of Hsp90 in tumours and support the development of Hsp90 therapeutics","authors":"Romy Cools,&nbsp;Valeria Narykina,&nbsp;Koen Vermeulen,&nbsp;Sanket J. Mishra,&nbsp;Brian S. J. Blagg,&nbsp;Marleen Derweduwe,&nbsp;Frederik De Smet,&nbsp;Aaron Ziani-Zeryouh,&nbsp;Matteo Riva,&nbsp;An Coosemans,&nbsp;Frederic Rousseau,&nbsp;Joost Schymkowitz,&nbsp;Guy Bormans","doi":"10.1186/s41181-025-00386-z","DOIUrl":"10.1186/s41181-025-00386-z","url":null,"abstract":"<div><h3>Background</h3><p>Hsp90 is a molecular chaperone that is often overexpressed across multiple cancer types and has a potential value as a prognostic marker as well as a therapeutic target. Given the high interest in Hsp90 therapies, positron emission tomography or PET imaging of Hsp90 can be a valuable tool for patient selection. The limitations of the previously developed Hsp90 tracers prompted us to evaluate the recently developed brain-permeable [¹¹C]HSP990 PET probe to advance the development of Hsp90-targeted therapeutics. Given the brain accumulation of [¹¹C]HSP990 probe, application for glioblastoma imaging of this tracer is of particular interest.</p><h3>Results</h3><p>In vitro [¹¹C]HSP990 binding was assessed in breast cancer and glioma cell lines including patient-derived cells using Hsp90 inhibitors and RNA interference knockdown of Hsp90 isoforms. Saturation binding studies were conducted on these cells and tumour tissue homogenates, and autoradiography was performed on tissue sections. Ex vivo biodistribution and in vivo dynamic µPET/CT studies were performed in healthy mice and tumour-bearing mice, including immunocompromised subcutaneous human U87 and MDA-MB-231models and immunocompetent intracranial murine NS/CT-2A models at baseline and following a pre-treatment with Hsp90 inhibitors. High Hsp90-specific tracer uptake was observed in breast cancer and glioma cells, with Hsp90β inhibition resulting in the most substantial reduction in uptake. In vivo uptake was high in U87 tumours but low in MDA-MB-231, presumably due to the differences in Hsp90 expression in tumour tissue <i>versus</i> cultured cells. Differences in maximum binding capacity or B_max across cell and tissue types support this hypothesis, especially given that the affinity measured as dissociation constant K_d remained similar across all tissue types. Despite high NS/CT-2A tumour uptake in vitro, no contrast between the healthy brain tissue and the NS/CT-2A glioma was observed in vivo due to the high uptake by the healthy brain.</p><h3>Conclusion</h3><p>[¹¹C]HSP990 is a promising tracer for identifying Hsp90-overexpressing tumours and may hold potential for patient stratification, prognosis, and therapy monitoring of novel Hsp90 therapeutics. High healthy brain uptake of this tracer precluded the differentiation of the tumour in the intracranial NS/CT-2A tumour model, therefore [¹¹C]HSP990 might not be a suitable tracer for the glioblastoma imaging. Tracer with a longer half-life might be needed to compare the washout of the tracer from the brain and the tumour tissue over several hours to identify a suitable imaging window.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00386-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147415","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":"Paving the way for future PSMA inhibitors: insights from comparative preclinical evaluations of structure modifications","authors":"Katarína Hajduová,&nbsp;Kateřina Dvořáková Bendová,&nbsp;Miloš Petřík,&nbsp;Martina Benešová-Schäfer,&nbsp;Martin Schäfer,&nbsp;Marián Hajdúch,&nbsp;Zbyněk Nový","doi":"10.1186/s41181-025-00389-w","DOIUrl":"10.1186/s41181-025-00389-w","url":null,"abstract":"<div><h3>Background</h3><p>Prostate-specific membrane antigen (PSMA) is an established target for the imaging and treatment of prostate cancer. This study focused on the preclinical evaluation of three novel PSMA inhibitors—P15, P16, and P19—which were structurally modified compared to the clinically used PSMA-617. Two main strategies were pursued: a chemical approach following the so-called reversed synthetic strategy, and the replacement of the naphthyl-based linker moiety with an analogous diphenyl-based moiety. The aim was to assess the impact of these modifications on physicochemical properties, in vitro behaviour, and in vivo pharmacokinetics following radiolabelling with ⁶⁸Ga.</p><h3>Results</h3><p>Radiolabelling of all three novel compounds with ⁶⁸Ga resulted in high radiochemical purity above 98% under physiological pH conditions and above 97% during stability testing in human plasma. All compounds exhibited hydrophilic characteristics based on partition coefficient measurements. Notable differences were observed in plasma protein binding, with P15 and P16 showing significantly lower binding compared to PSMA-617 and P19. In vitro assays using LNCaP prostate cancer cells demonstrated similar cellular uptake and internalization across all tested compounds. In vivo evaluation using Positron Emission Tomography/Computed Tomography (PET/CT) imaging in LNCaP tumour-bearing mice confirmed the tumour-targeting ability of all three inhibitors. These findings were further supported by biodistribution studies, which highlighted efficient and specific accumulation in tumour tissue. Among the tested compounds, P19 demonstrated the most promising overall profile in terms of stability, binding characteristics, and tumour uptake.</p><h3>Conclusions</h3><p>The stereochemical modifications in the linker region significantly influenced the in vitro and in vivo behaviour of the PSMA inhibitors. Despite similar cellular uptake, differences in plasma protein binding and pharmacokinetics were evident. Among the three novel compounds, P19 emerged as a particularly promising candidate for further investigation, also indicating that the diphenyl moiety might serve as a favourable linker building block in analogy to the naphthyl moiety. Our observations suggest potential not only for diagnostic imaging with ⁶⁸Ga, but also for therapeutic applications using ¹⁷⁷Lu, which offers a longer half-life suitable for delayed imaging and treatment intervals in prostate cancer management.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00389-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147427","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":"Design and characterization of a novel prostate-specific membrane antigen-targeted radioligand modified with a fatty acid albumin binder for optimized circulation half-life","authors":"Shaomei Zeng,&nbsp;Xiang Gao,&nbsp;Jiang Meng,&nbsp;Xudong Yang,&nbsp;Zhexin Chi,&nbsp;Yao Zhang,&nbsp;Ping Zhou,&nbsp;Min Li,&nbsp;Yi Zhang,&nbsp;Xiaodong Zhang,&nbsp;Yuanqing Tang,&nbsp;Zhonghai Su,&nbsp;Jun Tang","doi":"10.1186/s41181-025-00385-0","DOIUrl":"10.1186/s41181-025-00385-0","url":null,"abstract":"<div><h3>Background</h3><p>The March 2022 approval of [¹⁷⁷Lu]Lu-PSMA-617—the first targeted radioligand therapy (TRT) for metastatic castration-resistant prostate cancer (mCRPC)—addressed a critical need in therapeutic diagnostics. However, approximately 30% of patients fail to respond to PSMA-targeted therapies, with suboptimal pharmacokinetics implicated as a key factor. To address this challenge, fatty acids, known for their role in binding albumin and enhancing drug pharmacokinetics, were explored. Although commonly used in small molecules and peptides, their application in radiopharmaceuticals remains limited. In response, a novel fatty acid-modified PSMA-targeting agent was developed to optimize pharmacokinetics by enhancing circulation half-life, tumor uptake, radioligand selectivity, and safety while reducing off-target accumulation. This innovative approach aims to maximize therapeutic efficacy, improve patient outcomes in mCRPC care, and reduce the overall treatment burden.</p><h3>Results</h3><p>In vitro studies confirmed the strong binding affinity and high specificity of [¹⁷⁷Lu]Lu-BT-117016 for PSMA. Biodistribution studies in LNCaP clone FGC tumor-bearing mice demonstrated significantly enhanced tumor uptake and retention of [¹⁷⁷Lu]Lu-BT-117016 compared to [¹⁷⁷Lu]Lu-PSMA-617. SPECT/CT imaging and therapy studies highlighted the superior profile of [¹⁷⁷Lu]Lu-BT-117016. It achieved significant tumor growth suppression with favorable tolerability at a minimal dose of 3 MBq, demonstrating comparable efficacy to a nearly 6-fold higher dose (20 MBq) of [177Lu]Lu-PSMA-617. The improved safety profile of [¹⁷⁷Lu]Lu-BT-117016 over [¹⁷⁷Lu]Lu-PSMA-617 was confirmed through radiation dosimetry.</p><h3>Conclusion</h3><p>Preclinical studies demonstrate that [¹⁷⁷Lu]Lu-BT-117016, a novel fatty acid-modified PSMA-targeting agent, optimizes albumin binding and harmonizes ligand-isotope half-lives. This results in advantageous biodistribution—characterized by high tumor uptake, rapid non-target clearance, and extended circulation—leading to complete tumor remission in LNCaP models with reduced toxicity. Crucially, [¹⁷⁷Lu]Lu-BT-117016 achieved equivalent efficacy to [¹⁷⁷Lu]Lu-PSMA-617 at 3–6 times lower doses. These findings indicate [¹⁷⁷Lu]Lu-BT-117016’s potential as a safer, more potent CRPC therapy enabling reduced dosages and less frequent administration. Further clinical trials are warranted to confirm these benefits.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00385-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147391","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":"Brain-penetrating peptide and antibody radioligands for proof-of-concept PET imaging of fibrin in Alzheimer’s disease","authors":"Dag Sehlin,&nbsp;Ximena Aguilar,&nbsp;Marta Cortés-Canteli,&nbsp;Stina Syvänen,&nbsp;Sara Lopes van den Broek","doi":"10.1186/s41181-025-00383-2","DOIUrl":"10.1186/s41181-025-00383-2","url":null,"abstract":"<div><h3>Background</h3><p>Alzheimer’s disease (AD) is increasingly recognized as a multifactorial disorder with vascular contributions, including a pro-coagulant state marked by fibrin deposition in the brain. Fibrin accumulation may exacerbate cerebral hypoperfusion and neuroinflammation, leading to neurodegeneration. Identifying patients with this pathology could enable targeted anticoagulant therapy. However, current imaging tools lack the specificity and sensitivity to detect fibrin in the brain non-invasively. This study aimed to develop and evaluate brain-penetrating peptide- and antibody-based PET radioligands targeting fibrin to enable individualized treatment strategies in AD.</p><h3>Results</h3><p>A fibrin-binding peptide (FBP) was conjugated to the antibody fragment scFv8D3, which targets the transferrin receptor (TfR), to facilitate transcytosis across the blood-brain barrier. FBP-scFv8D3 bound TfR and with modest affinity to fibrin. In vivo studies in Tg-ArcSwe mice, that exhibit fibrin along with brain amyloid-β pathology, and wild-type mice showed that [¹²⁵I]FBP-scFv8D3 retained brain-penetrating properties but did not demonstrate significant fibrin-specific retention. In contrast, the monoclonal antibody 1101 and its bispecific, brain penetrant variant 1101-scFv8D3 exhibited higher fibrin selectivity and TfR binding. Both antibodies showed a trend towards higher brain retention in Tg-ArcSwe mice and [¹²⁵I]1101-scFv8D3 showed a higher brain-to-blood ratio compared to [¹²⁴I]1101. PET imaging with [¹²⁴I]1101 and [¹²⁴I]1101-scFv8D3 revealed low global brain uptake. However, ex vivo autoradiography and regional PET quantification (ROI-to-cerebellum ratios) indicated significant cortical and caudate retention of [¹²⁴I]1101-scFv8D3 in Tg-ArcSwe mice, supporting region-specific target engagement.</p><h3>Conclusion</h3><p>This proof-of-concept study demonstrates the feasibility of using bispecific antibody-based PET radioligands to target fibrin in the AD brain. While the FBP-scFv8D3 conjugate showed limited specificity, the bispecific antibody 1101-scFv8D3 exhibited higher brain penetration and fibrin selectivity. These findings support further development of antibody-based imaging tools toward the goal to stratify AD patients who may benefit from anticoagulant therapy.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00383-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011502","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 hydrogenation side-reaction in copper-mediated radiofluorination","authors":"Sarandeep Kaur,&nbsp;Barbara Wenzel,&nbsp;Ramona Oehme,&nbsp;Claudia Wiesner,&nbsp;Klaus Kopka,&nbsp;Rareş-Petru Moldovan","doi":"10.1186/s41181-025-00384-1","DOIUrl":"10.1186/s41181-025-00384-1","url":null,"abstract":"<div><h3>Background</h3><p>Copper-mediated radiofluorination (CMRF) is a breakthrough in ¹⁸F-radiochemistry, enabling ¹⁸F incorporation into molecules even at electron-rich aromatic positions. In recent years, several improved protocols have been reported to advance the application of CMRF. These advancements primarily focus on improving radiochemical conversion, expanding substrate scope, and enabling scalability for remote-controlled radiotracer production. Despite these improvements, one major challenge remains: the protodemetallation. Protodemetallation is a common side reaction in transition metal-mediated cross-couplings that takes place by a mechanism that is not yet fully elucidated. In ¹⁸F-chemistry, the formation of the hydrogenated side product (HSP) can interfere with the chromatographic purification of the desired radiotracer, resulting in complex radiotracer production.</p><h3>Results</h3><p>The present work investigates the factors influencing the rate of the hydrogenation reaction as well as the source of hydrogen in the CMRF by use of model precursors bearing -B(OH)₂, -Bpin, -BEpin and -SnBu₃ as leaving groups. While the CMRF reactions are usually carried out under anhydrous conditions, the formation rate of the HSP was evaluated by controlling the chemical constituents (type and molarity of reagents) as well as the physical parameters (time and temperature). Moreover, experiments with deuterated reagents complemented by high-resolution mass spectrometry (HRMS) analysis were carried out to identify the source of hydrogen for the reductive elimination step.</p><h3>Conclusion</h3><p>This study identifies reaction parameters that influence hydrogenation side reactions in CMRF, enabling high RCC with minimal HSP formation. The optimal reaction conditions include low temperature, short reaction time, and minimal amount of precursor, copper, and ideally no base and alcohols as solvents. Among the evaluated precursors, –BEpin afforded the lowest HSP formation, while –B(OH)₂ afforded the highest. Overall, this study showed that the selection of proper reaction reagents and the fine-tuning of reaction parameters can substantially reduce the HSP formation while maintaining optimal radiochemical conversion.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00384-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011503","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":"Cytotoxicity of 212Pb-labeled anti-PTK7 antibody in 2D adherent and 3D multicellular bladder cancer models","authors":"Kim Lindland,&nbsp;Asta Juzeniene","doi":"10.1186/s41181-025-00382-3","DOIUrl":"10.1186/s41181-025-00382-3","url":null,"abstract":"<div><h3>Background</h3><p> Bladder cancer remains a significant global health challenge, with approximately 75% of cases presenting as non-muscle-invasive bladder cancer. Despite standard treatment with transurethral resection and intravesical Bacillus Calmette-Guérin immunotherapy, up to 40% of patients develop resistance or progress to muscle-invasive disease. Targeted alpha-emitting radionuclide therapy offers promising therapeutic potential through the selective delivery of high linear energy transfer radiation to tumor cells while minimizing damage to healthy tissues. PTK7 is overexpressed in various malignancies, including bladder cancer, and is therefore a viable therapeutic target. This study evaluated the preclinical efficacy of [²¹²Pb]Pb-TCMC-chOI-1, a ²¹²Pb-labeled antibody targeting PTK7, for targeted alpha-emitting radionuclide therapy in bladder cancer using 2D adherent cultures (clonogenic assay) and 3D multicellular spheroid models (spheroid growth inhibition).</p><h3>Results</h3><p> PTK7 expression analysis revealed varying antigen densities across five bladder cancer cell lines, ranging from approximately 10,000 to 70,000 sites per cell. The chimeric anti-PTK7 antibody demonstrated apparent equilibrium dissociation constants of 10–44 nM with moderate binding affinity suitable for therapeutic applications. [²¹²Pb]Pb-TCMC-chOI-1 treatment resulted in activity- and time-dependent cytotoxicity, with enhanced sensitivity observed in cell lines with higher PTK7 levels. In clonogenic assays, the activity concentration required for 50% growth reduction was 48–74 kBq/mL, corresponding to 22–51 bound and 9–16 internalized ²¹²Pb atoms per cell. In 3D models, similar therapeutic effects were observed despite significantly lower activities (values of approximately 1 and 30 kBq/mL for KU-19–19 and 647-V cells, respectively), suggesting a more pronounced cross-fire effect. Flow cytometry demonstrated treatment-induced DNA damage, cell cycle perturbations and cell death, with response patterns correlating with overall treatment sensitivity. RT-112 and KU-19–19 cells showed superior responses compared to 647-V and T-24 cells, consistent with their higher PTK7 expression.</p><h3>Conclusions</h3><p> These findings support PTK7 as a therapeutic target for bladder cancer and demonstrate the potential of [²¹²Pb]Pb-TCMC-chOI-1 for targeted alpha-emitting radionuclide therapy. The results provide a rationale for further preclinical optimization of this therapeutic approach.</p><p><b>Trial registration number (TRN):</b> Not applicable.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00382-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920526","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":"Fibroblast activation protein expression in the tumor microenvironment is crucial in survival prediction and differentiation of recurrent gliomas: a head-to-head comparison of 68Ga-FAPI-04 and 18F-FET in PET/CT imaging","authors":"Tao Hua,&nbsp;Qi Huang,&nbsp;Zhirui Zhou,&nbsp;Weiyan Zhou,&nbsp;Jianbo Wen,&nbsp;Fang Xie,&nbsp;Ming Li,&nbsp;Yihui Guan,&nbsp;Dongxiao Zhuang","doi":"10.1186/s41181-025-00378-z","DOIUrl":"10.1186/s41181-025-00378-z","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;The precise differentiation of recurrent glioma from treatment-related changes, such as pseudoprogression or radiation necrosis, is essential for treatment planning and remains a significant challenge. Fibroblast activation protein (FAP) expressed by cancer-associated fibroblasts can be targeted with PET tracers for in vivo visualization and quantification. This study aims to evaluate the diagnostic and prognostic effectiveness of FAP expression in patients with potential recurrent glioma by directly comparing [gallium-68] FAP inhibitor-04 and [fluorine-18] fluoroethyl-L-tyrosine PET/CT imaging. Thirty glioma patients showing signs of possible recurrence during routine MRI follow-up after treatment were enrolled. PET-based semiquantitative parameters, clinical factors, and survival data were collected for analysis.&lt;/p&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Paired comparison of SUVmax, TBRmax, MTV, and TLU originating from two PET imaging studies indicated significant differences in TBRmax, MTV, and TLU, with P values of 0.000, 0.001, and 0.000, respectively. Univariate logistic regression analysis revealed a marginally non-significant difference in efficacy (&lt;i&gt;P&lt;/i&gt; = 0.053) of the initial pathological diagnosis. In multivariate logistic regression analysis, PET parameters, initial pathological data, age, and gender were used to develop the predictive models step by step. Although trends towards significance were observed in the MTV&lt;sub&gt;FAPI&lt;/sub&gt;:MTV&lt;sub&gt;FET&lt;/sub&gt; ratio, no PET parameters reached statistical significance. The MTV&lt;sub&gt;FAPI&lt;/sub&gt;:MTV&lt;sub&gt;FET&lt;/sub&gt; ratio improved the area under the receiver operating characteristic curve (AUC). When PET parameters and initial pathological diagnosis were included, the MTV&lt;sub&gt;FAPI&lt;/sub&gt;:MTV&lt;sub&gt;FET&lt;/sub&gt; ratio significantly enhanced the model’s AUC (&lt;i&gt;P&lt;/i&gt; = 0.040) from 0.709 (0.465–0.953, 95% CI) to 0.847 (0.688-1.000, 95% CI). When replacing the initial diagnosis with initial WHO grade, the MTV&lt;sub&gt;FAPI&lt;/sub&gt;:MTV&lt;sub&gt;FET&lt;/sub&gt; ratio improved the AUC (&lt;i&gt;P&lt;/i&gt; = 0.016) from 0.640 (0.400–0.880, 95% CI) to 0.852 (0.715–0.988, 95% CI). After factoring in age and gender in addition to the initial pathological diagnosis, the MTV&lt;sub&gt;FAPI&lt;/sub&gt;:MTV&lt;sub&gt;FET&lt;/sub&gt; ratio enhanced the AUC (&lt;i&gt;P&lt;/i&gt; = 0.039) from 0.841 (0.677-1.000, 95% CI) to 0.963 (0.887-1.000, 95% CI). Similarly, after replacing the initial pathological diagnosis with the initial WHO grade, the MTV&lt;sub&gt;FAPI&lt;/sub&gt;:MTV&lt;sub&gt;FET&lt;/sub&gt; ratio significantly enhanced the AUC of the model (&lt;i&gt;P&lt;/i&gt; = 0.046) from 0.762 (0.532–0.992, 95% CI) to 0.942 (0.850-1.000, 95% CI). The survival analysis revealed that the MTV-FAPI of the lesion has a significant impact on overall survival (&lt;i&gt;P&lt;/i&gt; = 0.027, hazard ratio = 1.103, 95% CI: 1.011–1.204).&lt;/p&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;This head-to-head exploratory study showed that glioma FAP expression volume is an independent risk factor that can significantly influence overall survival in patients with rec","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00378-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897195","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":"Compact accelerator-based production of carrier-free 177Lu from 18 MeV (D^+) on [176Yb](hbox {Yb}_2hbox {O}_3)","authors":"Austin A. Morris,&nbsp;Tianhao Wei,&nbsp;Zhi Wang,&nbsp;Ying Xia,&nbsp;Meiyun Han,&nbsp;Yuanrong Lu","doi":"10.1186/s41181-025-00358-3","DOIUrl":"10.1186/s41181-025-00358-3","url":null,"abstract":"<div><h3>Background</h3><p>Recent EMA and FDA approvals of Lu-DOTATATE and Lu-PSMA-617 have led to increased demand for radiotherapeutic <span>(^{177})</span>Lu, due to its promising potential to treat castration-resistant neuroendocrine cancers. Conventional reactor production methods pose challenges related to cost, waste management, and local availability. In comparison, accelerators produce less waste, have lower maintenance costs, and can be directly integrated into hospital settings. In this study, we evaluate the production of radiotherapeutic <span>(^{177})</span>Lu using a 10 mA, 18 MeV <span>(D^+)</span> compact linear accelerator design. The design consists of a single radio-frequency quadrupole (RFQ) and seven drift tube linacs (DTLs) that achieve a beam efficiency of 98.5% over a total length of <span>(12,text {m})</span>. Deuteron activations on a 99% enriched [<span>(^{176})</span>Yb]<span>(hbox {Yb}_2hbox {O}_3)</span> target are estimated using experimental and simulated excitation functions.</p><h3>Results</h3><p>A circular target with a radius of 1 cm and 0.36 mm thickness is selected to optimize the yield of <span>(^{177})</span>Lu while minimizing the production of undesirable radioisotopes, including <span>(^{174g+m})</span>Lu and <span>(^{177m})</span>Lu. Model calculations indicate that the accelerator design can produce 11.3 μg of <span>(^{177})</span>Lu per hour. A 5-day irradiation is expected to yield approximately 1.07 mg of <span>(^{177})</span>Lu (4.4 TBq), while a 12-day irradiation can produce up to 1.9 mg (7.8 TBq). Following a 2-day processing period, the specific activity of the 5-day irradiated sample is projected to approach 0.6 TBq/mg, with a radiopurity of approximately 99.8%. The minimal burn-up of the <span>(hbox {Yb}_2hbox {O}_3)</span> target suggests it may be recycled and reused over multiple irradiations.</p><h3>Conclusions</h3><p>The study confirms the feasibility of accelerator-based <span>(^{177})</span>Lu production as an alternative to existing reactor-based methods. The 10 mA, 18 MeV <span>(D^+)</span> RFQ-DTL design achieves an exceptionally high <span>(^{177})</span>Lu radiopurity and a competitive overall yield, which can meet the dose requirements of thousands of patients.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00358-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896899","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}