EJNMMI Radiopharmacy and Chemistry最新文献

{"title":"MUC1-targeting small peptide radiopharmaceuticals for breast cancer.","authors":"Rim Malek, Madeleine Landry, Pierre Cheung, Corinne Beinat","doi":"10.1186/s41181-026-00451-1","DOIUrl":"https://doi.org/10.1186/s41181-026-00451-1","url":null,"abstract":"<p><strong>Background: </strong>Mucin 1 (MUC1) is a transmembrane glycoprotein overexpressed and underglycosylated in numerous epithelial cancers, including breast cancer. Reduced glycosylation leads to the exposure of the variable number tandem repeat (VNTR) region. To the best of our knowledge, all peptides previously described in the literature target the same epitope sequence of the VNTR. Given the high prevalence of breast cancer and the limited treatment options for the aggressive subtype triple-negative breast cancer (TNBC), due to its lack of oestrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2), we sought to develop a small peptide radiopharmaceutical targeting MUC1 by exploring all 3 minimal epitope sequences of the VNTR: RPAPGS, PPAHGVT and PDTRP. We also investigated the influence of linker lipophilicity on the binding affinity to MUC1.</p><p><strong>Results: </strong>The reference compound 1 showed the highest cell uptake among all tested compounds. While some statistically significant differences were observed for the cell uptake between the different peptide sequences and the linkers, the uptake was so low that no reliable structure-activity relationships could be established. We then studied the specificity of all compounds for MUC1 by comparing the uptake in MUC1-expressing and MUC1-knockout (KO) cells, and unexpectedly observed no specificity for any compound. A saturation binding assay of several peptides showed their binding was too low to reliably determine their binding affinity (K_d). Surface plasmon resonance (SPR) further confirmed the absence of binding of all [^NatGa]- and [^NatLu]-labelled peptides tested. Given the discrepancies between our cell data and the previously reported results, we next assessed the specificity of the reference (1) in vivo in mice bearing MUC1-expressing and MUC1-knockdown (KD) tumours, which further proved its non-specificity.</p><p><strong>Conclusions: </strong>While MUC1 is a very promising target for the development of breast cancer theranostics, designing peptidomimetics based on its minimal epitopes do not lead to high-affinity binders. Our ongoing efforts involve utilizing phage-display to identify new peptide sequences.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809472","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}

{"title":"Radiation stability and performance of TEHDGA resin for theranostic scandium radionuclide purification.","authors":"Rudolfs Janis Zabolockis, Edgars Mamis, Laura Dace Pakalniete, Liga Avotina, Maris Bertins, Janis Sadauskis, Aina Semjonova, Jarosław Sadło, Magdalena Rzepna, Jevgenijs Proskurins, Elina Pajuste","doi":"10.1186/s41181-026-00450-2","DOIUrl":"https://doi.org/10.1186/s41181-026-00450-2","url":null,"abstract":"<p><strong>Background: </strong>Scandium radionuclides are emerging theranostic radionuclides that offer matched diagnostic and therapeutic emissions for targeted applications in nuclear medicine. For their safe and effective clinical use, it is crucial to obtain preparations with very high radiochemical purity, which in turn relies on carefully optimized physical separation and chemical purification strategies. A selective and clinically attractive method for purification is ion-exchange solid-phase extraction; however, its performance and expected resin lifetime under high radiation doses and repeated separation cycles remains insufficiently considered. This study provides a critical evaluation of the radiation stability and separation performance of the N, N,N',N'-tetra(2-ethylhexyl)diglycolamide (TEHDGA) ion-exchange resin.</p><p><strong>Results: </strong>Monte Carlo simulations in RayXpert^® show that assuming 1 GBq ⁴⁴Sc and 3.7 GBq ⁴⁷Sc initial activities (possible theranostic activities) a total absorbed dose of ~ 1 kGy could be expected for ⁴⁴Sc and ~ 5 kGy for ⁴⁷Sc in one purification experiment. EPR spectra show that after irradiation the TEHDGA resin does not form room temperature stable radicals; however, the resin appears to change its chemical structure upon irradiation with electrons in a nitric acid environment, as indicated by ATR-FTIR measurements. However, these chemical changes can be estimated to have little-to-no effect on the practical application of TEHDGA in scandium ion purification, yielding separation efficiency from contaminants of at least 99% for resin irradiated in 2.5 M HNO₃, whereas irradiation in air yielded a minimum separation efficiency of 96%. No clear changes in selectivity, ion-exchange capacity or recoverability have been observed.</p><p><strong>Conclusions: </strong>TEHDGA resin can be deemed suitable for theranostic scandium radionuclide purification from metallic contaminants; however, further research is needed to assess the possible transient effects of short-lived radiolysis intermediates during practical scandium radionuclide purification.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759096","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}

{"title":"Radionuclide-based pharmaceuticals for breast cancer imaging: state of the art.","authors":"P Paraïso, C H M van Deurzen, Y Seimbille","doi":"10.1186/s41181-026-00446-y","DOIUrl":"https://doi.org/10.1186/s41181-026-00446-y","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is a biologically heterogeneous disease, and no single imaging modality captures the full spectrum of phenotypes across all stages of the disease. This review summarizes advances in receptor-targeted nuclear imaging approaches that support patient stratification, treatment selection and response monitoring.</p><p><strong>Main body: </strong>We provide a comprehensive review of preclinical and clinical studies of PET and SPECT radiopharmaceuticals targeting BC-relevant biomarkers on tumor cells and within the tumor microenvironment, with emphasis on clinical use cases, practical limitations and theranostic translational readiness. Conventional imaging modalities and [¹⁸F]FDG PET/CT remain central to staging but can be limited by poor specificity and reduced sensitivity for small lesions. Although anatomical (RECIST) and metabolic (PERCIST) response criteria remain central in routine response assessment, their application in BC can be challenging, particularly in bone-predominant disease and in the presence of marked inter-lesional heterogeneity. Receptor-mediated nuclear imaging enables non-invasive, whole-body phenotyping beyond biopsy and maps spatial heterogeneity. Clinical progress has been achieved for steroid receptors (ER/PR/AR), HER2, GRPR and SSTR2 imaging, and extends to stromal targets such as FAP (FAPI tracers). Emerging targets, including CXCR4, NTSR1, NPY1R and TROP-2, further broaden the theranostic landscape, particularly in settings where biomarker profiles are heterogeneous or evolve over time.</p><p><strong>Conclusion: </strong>Multi-target imaging strategies may better address intra- and inter-lesional heterogeneity. Larger prospective cohorts are needed to define diagnostic performance, clinical relevance and theranostic value in BC.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759110","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}

{"title":"Clinical nuclear medicine applications of zirconium-89 immuno-PET: a comprehensive review from a radiopharmaceutical perspective","authors":"Julien Dubois,&nbsp;Emmanuel Deshayes,&nbsp;Florentin Kucharczak,&nbsp;Marine M. Cadet,&nbsp;Jifang Zhou,&nbsp;Tom Paunet,&nbsp;Cyril Fersing","doi":"10.1186/s41181-025-00418-8","DOIUrl":"10.1186/s41181-025-00418-8","url":null,"abstract":"<div><h3>Background</h3><p>Immuno-positron emission tomography (immuno-PET) imaging is emerging as a highly promising technique for the non-invasive diagnosis of a wide range of pathological conditions, particularly in oncology and immunology. This molecular imaging modality enables the visualization, characterization, and quantification of biological processes at a cellular and molecular level.</p><h3>Main body</h3><p>Immuno-PET relies mostly on the administration of monoclonal antibodies (mAb) labeled with positron-emitting radionuclides. These antibodies are specifically designed to bind to antigens that are overexpressed on tumor cells or involved in pathological non-neoplastic processes, such as inflammatory or autoimmune diseases. Numerous disease-associated antigens have been identified and are currently being explored as potential molecular targets for immuno-PET, paving the way for more personalized diagnostic and treatment approaches. This technique offers significant potential in the context of theranostic, as it allows for the simultaneous assessment of both diagnostic and therapeutic parameters. It is particularly useful for predicting and monitoring the pharmacokinetics and biodistribution of targeted therapies, thereby helping to optimize therapeutic efficacy while minimizing adverse effects. Among the various radioisotopes available, zirconium-89 (⁸⁹Zr) has gained attention as a particularly suitable candidate for mAb labeling due to its favorable physicochemical characteristics such as its half-life (78.4 h), which matches well with the slow kinetics of intact antibodies, and its appropriate positron emission profile for high-resolution imaging. Despite the growing interest in immuno-PET and the increasing number of radiolabeling protocols described in the literature, the clinical implementation of ⁸⁹Zr-labeled mAbs faces numerous challenges. These include logistical and technical hurdles, but more significantly, regulatory obstacles that vary across countries and between regulatory authorities, particularly within Europe. Such disparities hinder the harmonization of clinical trials and limit access to immuno-PET technologies for many research centers.</p><h3>Conclusion</h3><p>In this review, we aim to provide an overview of the current clinical applications of ⁸⁹Zr-labeled mAbs, based on published studies and ongoing trials, and highlight the key challenges that need to be addressed to expand access to this powerful imaging modality.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-025-00418-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147737980","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 of automated radiosynthesis method for [¹⁸F]AlF-NOTA-Octreotide and PET/CT imaging in neuroendocrine neoplasms.","authors":"Xiaoting Wan, Jiangyue Yan, Jieting Hu, Ruiyun Zhang, Shiliang Zhu, Hao Sun, Jingwen Cao, Kaixuan Li, Dacan Yang, Lingyun Yang, Kaizhen Xianyu, Di Xia, Zijian He, Dan Li","doi":"10.1186/s41181-026-00447-x","DOIUrl":"https://doi.org/10.1186/s41181-026-00447-x","url":null,"abstract":"<p><strong>Background: </strong>Neuroendocrine neoplasms (NENs) represent heterogeneous tumors with increasing occurrence rate. Somatostatin receptor (SSTR) imaging using ⁶⁸Ga-labeled analogs is crucial but limited by the relatively short half-life of this radionuclide along with its reliance on generator supply. To overcome these limitations, this study aimed to establish an automated synthesis platform compliant with Good Manufacturing Practice (GMP) standards for the preparation of a novel SSTR-targeting probe, [¹⁸F]AlF-NOTA-octreotide. Its diagnostic efficacy in neuroendocrine neoplasms was evaluated through comparison with existing ⁶⁸Ga-labeled and [¹⁸F]FDG probes.</p><p><strong>Results: </strong>The fully automated-synthesis of [¹⁸F]AlF-NOTA-Octreotide was completed within 37 minutes, with a specific activity of 56 ± 5 GBq/μmol and a radiochemical yield (RCY) of 42 ± 1.5%. The RCP was > 95% and remained stable for 8 hours at room temperature. The [⁶⁸Ga]Ga-NOTA-Octreotide kit demonstrated an RCP of 97.5 ± 0.3%, stability ≥94% for 4 hours, and long-term stability ≥ 96% over 6 months. In vivo imaging in mice showed comparable tumor uptake for both probes at 30 minutes post-injection (5.6 %ID/cc). However, [¹⁸F]AlF-NOTA-Octreotide exhibited significantly lower background activity in blood, muscle, and bone. The tumor uptake of [¹⁸F]AlF-NOTA-Octreotide remained high (5.92 ± 0.10 %ID/cc) at 2 hours post-injection, superior to that of the ⁶⁸Ga-labeled counterpart (5.05 ± 0.68 %ID/cc). At the patient level, [¹⁸F]AlF-NOTA-Octreotide detected 41 (87.2%) among 47 lesions, whereas [¹⁸F]FDG detected only 13 (27.7%). For G1-G2 grade lesions, the SUVmax was significantly higher with [¹⁸F]AlF-NOTA-Octreotide compared to [¹⁸F]FDG (14.9 ± 13.8 to 4.8 ± 4.4, p < 0.001). [¹⁸F]AlF-NOTA-Octreotide demonstrated superior detection of primary tumors, lymph node metastases, hepatic, osseous, and peritoneal metastases compared to FDG. One case of pulmonary atypical carcinoid (G3) was FDG-positive but Octreotide-negative, illustrating the complementary nature of the two imaging modalities.</p><p><strong>Conclusions: </strong>A robust, GMP-compatible automated synthesis process for [¹⁸F]AlF-NOTA-Octreotide and a lyophilized kit for [⁶⁸Ga]Ga-NOTA-Octreotide were successfully established, both exhibiting high RCP, high specific activity, and excellent stability. [¹⁸F]AlF-NOTA-Octreotide demonstrated significantly higher lesion detection rates and uptake intensity than [¹⁸F]FDG in SSTR2-positive NENs with lower background activity. The complementary profiles of these probes enable personalized, precise imaging based on tumor biology. This work provides substantial technical and data support for clinical translation.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759148","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}

{"title":"A 3D co-culture model with fibroblast-restricted FAP expression for cancer therapy using [²¹²Pb]Pb-FAPI-46.","authors":"Sandra K Kristiansen, Nurtene Dernjani, Øyvind S Bruland, Nina Frederike J Edin, Asta Juzeniene","doi":"10.1186/s41181-026-00444-0","DOIUrl":"https://doi.org/10.1186/s41181-026-00444-0","url":null,"abstract":"","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715507","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}

{"title":"Radiolabeling efficiency of FENTA chelators and stability of their terbium-161, lutetium-177 and bismuth-213 complexes.","authors":"Cédric Bonneux, Sunay Rodríguez Pérez, Stephan Heinitz, Veronique Bogaerts, Michiel Van de Voorde, Thomas Cardinaels, Maarten Ooms, Wim Dehaen, Tomas Opsomer","doi":"10.1186/s41181-026-00438-y","DOIUrl":"https://doi.org/10.1186/s41181-026-00438-y","url":null,"abstract":"<p><strong>Background: </strong>Phenanthroline derivatives are well-known chelators in coordination chemistry, but their potential in the rapidly evolving field of targeted radionuclide therapy (TRT) has not yet been explored. In TRT, DOTA remains the gold standard chelator for several clinically relevant radionuclides such as terbium-161, lutetium-177 and bismuth-213. However, its requirement for elevated labeling temperatures is a drawback, particularly for heat-sensitive targeting vectors. Although several alternative chelators have been reported in recent years, there remains an interest in new systems with suitable complexation properties. In this work, we evaluate whether phenanthroline-based ligands can serve as useful chelators in TRT, using the octadentate chelator H₄FENTA and a newly developed bifunctional analog, BF-FENTA. Their ability to complex [¹⁶¹Tb]Tb³⁺, [¹⁷⁷Lu]Lu³⁺, and [²¹³Bi]Bi³⁺, as well as their kinetic inertness, was assessed and compared to the benchmark chelators DOTA and CHX-A\"-DTPA.</p><p><strong>Results: </strong>BF-FENTA was prepared via mono-substitution of 2,9-bis(chloromethyl)-1,10-phenanthroline with di-tert-butyl iminodiacetate, followed by a second substitution with the bifunctional arm. Both H₄FENTA and BF-FENTA efficiently incorporated [¹⁶¹Tb]Tb³⁺ under mild conditions within 15 min at an apparent molar activity (AMA) of 150 MBq/nmol. Stability studies showed that both chelators formed an unstable complex with [¹⁶¹Tb]Tb³⁺, while the [¹⁷⁷Lu]Lu³⁺ chelates showed similar stability compared to DOTA after 7 days in human serum. However, a DTPA challenge indicated a reduced kinetic inertness for both FENTA chelators compared to DOTA. For [²¹³Bi]Bi³⁺, rapid incorporation was observed with the phenanthroline chelators, with H₄FENTA achieving high radiochemical conversions (> 90%) at high AMAs of up to ~ 200 MBq/nmol after 5 min. Additionally, H₄FENTA displayed a high selectivity for [²¹³Bi]Bi³⁺ in the presence of competing metal ions. BF-FENTA showed slightly less favorable chelation properties with [²¹³Bi]Bi³⁺ compared to H₄FENTA. Nonetheless, the [²¹³Bi]Bi³⁺ complexes remained intact in both buffer (NH₄OAc, pH 6.0) and human serum after 90 min.</p><p><strong>Conclusion: </strong>Both H₄FENTA and BF-FENTA rapidly incorporated terbium-161, lutetium-177, and bismuth-213. While the kinetic inertness of their terbium-161 and lutetium-177 complexes was inadequate, H₄FENTA exhibited favorable kinetic inertness with bismuth-213 over the 90 min timeframe, identifying it as a promising chelator. In contrast, further structural refinement is needed for its bifunctional analog.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147626559","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}

{"title":"Comparison of two ¹⁸F-fluorinated glycopeptides for PET imaging of the functional liver mass.","authors":"Maximilian A Zierke, Katharina Hofer, Kimia Samadikhah, Christine Rangger, Carmen Wängler, Björn Wängler, Anna Junker, Andreas M Schmid, Roland Haubner","doi":"10.1186/s41181-026-00445-z","DOIUrl":"https://doi.org/10.1186/s41181-026-00445-z","url":null,"abstract":"<p><strong>Background: </strong>The non-invasive determination of the asialoglycoprotein receptor (ASGR) expression on liver tissue might be a predictive parameter helping to prevent severe liver diseases as well as liver failure after surgery and transplantation. Recently, we introduced [⁶⁸Ga]Ga-NODAGA-NonaLysan, which showed even a higher liver uptake as the gold standard [^99mTc]Tc-Galactosyl Serum Albumin. Here we describe the synthesis and evaluation of two ¹⁸F-labeled analogues, prepared using either a SiFA- or an AlF-labeling approach.</p><p><strong>Results: </strong>The two precursors could be produced in high purity (> 97%). Both labeling strategies allowed production of the radiopharmaceuticals in high radiochemical purity. The radiochemical yield was up to 58% d.c. for [¹⁸F]SiFA-NonaLysan and up to 71% d.c. for Al[¹⁸F]F-NOTA-6-Ahx-NonaLysan. In vitro evaluation showed high stability in PBS and human serum. Both compounds possessed nanomolar affinity for the ASGR (IC₅₀ = 0.9 ± 1.1 nM and 3.0 ± 2.1 nM, respectively). However, based on the design differences, Al[¹⁸F]F-NOTA-6-Ahx-NonaLysan showed a 100-fold lower logD as found for [¹⁸F]SiFA-NonaLysan. In consequence, the protein binding effect was higher for [¹⁸F]SiFA-NonaLysan, and the lipophilic character drastically affected the pharmacokinetic pattern. Initial liver uptake was higher for [¹⁸F]SiFA-NonaLysan (100% ID/g vs. 70% ID/g 10 min p.i.), but was accompanied by a quick organ washout and activity accumulation in the intestines. A much better activity retention was observed for Al[¹⁸F]F-NOTA-6-Ahx-NonaLysan. PET/MR imaging confirmed the differences in liver uptake, with a higher retention found for the latter. Based on the receptor function, both compounds are internalized and subsequently degraded. For Al[¹⁸F]F-NOTA-6-Ahx-NonaLysan, all radioactive liver metabolites found were more hydrophilic than the intact compound. For [¹⁸F]SiFA-NonaLysan, the contrary is the case, and almost all liver metabolites were more lipophilic. The hepatobiliary excretion of these metabolites prevents a stable activity retention in the hepatic tissue.</p><p><strong>Conclusion: </strong>In this study, we successfully synthesized two new ¹⁸F-labeled radiopharmaceuticals targeting the ASGR. The in vivo evaluation revealed two different pharmacokinetic profiles. Extremely high uptake was found for [¹⁸F]SiFA-NonaLysan in the initial phase, followed by a quick organ washout. Al[¹⁸F]F-NOTA-6-Ahx-NonaLysan showed a lower but more stable activity retention in the liver, indicating advantageous imaging properties.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618370","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}

{"title":"The use of mass cytometry (CyTOF) to evaluate the cellular uptake of stable radiopharmaceutical surrogates in single cells: a proof-of-concept study","authors":"Miguel Gómez-Sánchez,&nbsp;Elisa Blanco-González,&nbsp;María Montes-Bayón,&nbsp;Martin Behe,&nbsp;Roger Schibli,&nbsp;Elisa Rioja-Blanco","doi":"10.1186/s41181-026-00442-2","DOIUrl":"10.1186/s41181-026-00442-2","url":null,"abstract":"<div><h3>Background</h3><p>Current methods for assessing radiopharmaceutical uptake are based on scintillation counting (e.g., γ-counting) or imaging techniques, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), which evaluate the average radiopharmaceutical uptake in biological samples. Single-cell analysis of radiopharmaceutical uptake and biodistribution would provide a better understanding of the possible heterogeneous uptake in cellular populations and organs, with the potential to improve current dosimetry and toxicity assessments. In this proof-of-concept study, we evaluate the use of mass cytometry (CyTOF) as an analytical tool to study the uptake of non-radioactive radiopharmaceutical surrogates at the single-cell level.</p><h3>Results</h3><p>The preclinical immunoconjugate DOTA-cAC10, targeting CD30 (a receptor overexpressed in lymphomas), was labeled either with radioactive lutetium-177 (¹⁷⁷Lu) resulting in the [¹⁷⁷Lu]Lu-DOTA-cAC10 radioimmunoconjugate, or stable lutetium-175 (¹⁷⁵Lu), yielding the surrogate [¹⁷⁵Lu]Lu-DOTA-cAC10. For CyTOF experiments, cells were incubated with the stable surrogate and an iridium DNA intercalator (Cell-ID™) to enable concurrent determination of immunoconjugate uptake and cell identification. CyTOF analysis of the surrogate was performed in three T-cell lymphoma cell lines with varying CD30 expression (Karpas 299, Myla and Jurkat) and compared to γ-counting data obtained for the radioimmunoconjugate. Radioimmunoconjugate [¹⁷⁷Lu]Lu-DOTA-cAC10 cellular uptake studies by γ-counting showed receptor-dependent accumulation, with Karpas 299 cells exhibiting the highest uptake levels (32.5 ± 1.6% of total added activity), followed by Myla (20.0 ± 1.0%) and Jurkat cells (15.7 ± 1.2%). Mass cytometry enabled analysis of the stable surrogate [¹⁷⁵Lu]Lu-DOTA-cAC10 uptake at single-cell resolution, revealing median signal intensities of ¹⁷⁵Lu of 32.2, 14.0, and 2.94 a.u. for Karpas 299, Myla, and Jurkat cells, respectively.</p><h3>Conclusions</h3><p>The sensitivity of CyTOF enabled discrimination of uptake between cell models even at low metal-to-antibody stoichiometric ratios. It also revealed intercellular variability in uptake that can only be captured with single-cell methods. Overall, we showed that CyTOF is a robust, high-throughput, multiplexed approach for characterizing the cellular uptake of stable radiopharmaceutical surrogates at single-cell resolution, paving the way for future studies.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00442-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589229","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":"Redox-driven speciation and colloid formation contribute the in vivo chemistry and organ deposition of Astatine-211.","authors":"Xiaoxu Dong, Jiaojiao Li, Mumei Chen, Kaiqi Zhang, Xiaozheng Zhang, Fengling Shan, Shuai Xue, Xiao Li, Lan Zhang, Huawei Cai, Jiajun Liu, Qingnuan Li","doi":"10.1186/s41181-026-00441-3","DOIUrl":"https://doi.org/10.1186/s41181-026-00441-3","url":null,"abstract":"<p><strong>Background: </strong>Astatine-211 (²¹¹At) is a promising radionuclide for targeted alpha therapy (TAT), yet its clinical translation is hindered by poor in vivo stability and pronounced non-target organ accumulation. The fundamental radiochemical mechanisms governing the biodistribution of free ²¹¹At remain insufficiently understood, limiting rational radiopharmaceutical design.</p><p><strong>Results: </strong>Comparative in vivo studies revealed that free ²¹¹At and free iodine-131 (¹³¹I) initially share similar distribution patterns but diverge markedly thereafter, with ²¹¹At exhibiting pronounced accumulation in the stomach, lungs, liver, and spleen. Experimental speciation analyses demonstrated rapid oxidation of At^- to cationic intermediates in biological environments, followed by hydrolysis and colloid formation. Ultrafiltration and chromatography confirmed the generation of macromolecular species responsible for hepatosplenic retention. Co-administration of ascorbic acid (AA) partially suppressed abnormal organ uptake, supporting a redox-dependent mechanism. Density functional theory (DFT)-based Pourbaix analysis further corroborated the thermodynamic instability of At^- under physiological conditions and predicted the predominance of oxidized and hydrolyzed species.</p><p><strong>Conclusions: </strong>These results identify redox-driven speciation and subsequent hydrolysis/aggregation as key chemical processes contributing to the in vivo behavior of free ²¹¹At. Understanding and controlling astatine redox chemistry is therefore critical for improving the stability, safety, and translational development of ²¹¹At-based radiopharmaceuticals.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589217","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}