EJNMMI Radiopharmacy and Chemistry最新文献

{"title":"Structure–activity relationship of 18F-labeled PD-L1-targeting small molecule ligands: impact of radiolabeling strategy on affinity and in vivo performance","authors":"Fabian Krutzek,&nbsp;Cornelius K. Donat,&nbsp;Sven Stadlbauer","doi":"10.1186/s41181-025-00359-2","DOIUrl":"10.1186/s41181-025-00359-2","url":null,"abstract":"<div><h3>Background</h3><p>Immune checkpoint inhibitor therapy addressing the PD-1/PD-L1 axis is a promising approach in cancer treatment. A clinically suitable radiotracer would allow molecular imaging of the temporospatial changes in tumor PD-L1 expression. This could enable the clinicians to select eligible patients for checkpoint therapy and monitor therapeutic efficacy.</p><h3>Results</h3><p>Four biphenyl-based small-molecule PD-L1 ligands were synthesized using a convergent synthetic route, with a linear sequence of up to eleven steps. Two candidates were covalently labeled with ¹⁸F via either an azido glycosyl or PEG2 moiety, while the other two were modified with a RESCA chelator for Al[¹⁸F]F²⁺-labeling. The lipophilicity was assessed through determination of log <i>D</i>_7.4 values. In vitro binding affinities (inhibition constant, <i>K</i>_i) toward PD-L1 were determined in competition with one of our previously published biphenyl-based small-molecule (<i>K</i>_D =  ~ 21 nM). Compared to this compound, both covalently labeled ¹⁸F-ligands exhibited decreased water solubility (log <i>D</i>_7.4 ~ − 2.5 and − 2.7), along with a markedly reduced (<i>K</i>_i = 200‒500 nM) affinity. This was in line with in vivo small animal PET, where both compounds were characterized by a negligible tumor uptake, lack of contrast between target-positive/negative tumors and exclusively unfavorable hepatobiliary excretion. Similar results were observed for the chelator-modified ligands with slightly increased hydrophilicity (log <i>D</i>_7.4 ~ − 2.8 and − 2.9), showing a binding affinity of 150 nM for one compound, while binding was lost completely for the other. Again, a poor in vivo performance was observed, characterized by hepatobiliary clearance and lack of specific tumor uptake in the PD-L1 positive tumor.</p><h3>Conclusion</h3><p>Four biphenyl-based, ¹⁸F-labeled PD-L1 radioligands were developed using prosthetic groups (azido glycosyl or PEG2) for covalent fluorination and Al[¹⁸F]F²⁺-complexation with the RESCA chelator. Despite limited in vitro and in vivo performance, these fluorination approaches offer a foundation for developing improved PD-L1 radioligands after increasing the hydrophilicity and the spacing between the radiolabel and binding motif.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537579","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":"Protein-based Radiopharmaceuticals that target fibroblast activation protein alpha: a review of current progress","authors":"Abdelrahman Homedan,&nbsp;Darpan N. Pandya,&nbsp;Nicholas J. Schnicker,&nbsp;Thaddeus J. Wadas","doi":"10.1186/s41181-025-00356-5","DOIUrl":"10.1186/s41181-025-00356-5","url":null,"abstract":"<div><h3>Background</h3><p>Fibroblast activation protein alpha (FAP) is a serine protease that is expressed at basal levels in benign tissues but is overexpressed in a variety of pathologies, including cancer. Consequently, significant research efforts have been expended to develop diagnostic radiopharmaceuticals and effective radiotherapies that target this protein. The aim of this review is to summarize the current progress on the development of protein-based radiopharmaceuticals that target FAP.</p><h3>Main body</h3><p>A literature survey spanning nearly 40 years was conducted to assess the historical development and current progress in protein-based radiopharmaceuticals that target FAP. To date, more than 20 publications have been introduced that describe these agents in preclinical and clinical settings. This review summarizes the development and evaluation of radiopharmaceuticals involving antibodies, antibody fragments, and single domain antibodies.</p><h3>Conclusion</h3><p>The results of this literature review demonstrate that while significant research efforts have been expended on peptide-based radiopharmaceuticals and small molecule FAP inhibitors, the development of protein-based radiopharmaceuticals that target FAP remains an active research area that has yet to reach its full potential. </p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339704","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":"It’s a match: use of the radionuclide theranostic pair 133La/225Ac for the radiopharmacological characterization of EGFR-targeted single-domain antibodies","authors":"Johanna Trommer,&nbsp;Martin Ullrich,&nbsp;Falco Reissig,&nbsp;Santiago Andres Brühlmann,&nbsp;Anne-Kathrin Nitt-Weber,&nbsp;Zbynek Novy,&nbsp;Katarina Hajduova,&nbsp;Daniela Kurfurstova,&nbsp;Romana Hendrychova,&nbsp;Jan Bouchal,&nbsp;Milos Petrik,&nbsp;Christin Neuber,&nbsp;Wiebke Sihver,&nbsp;Sven Stadlbauer,&nbsp;Jens Pietzsch,&nbsp;Martin Kreller,&nbsp;Klaus Kopka,&nbsp;Constantin Mamat,&nbsp;Kristof Zarschler","doi":"10.1186/s41181-025-00354-7","DOIUrl":"10.1186/s41181-025-00354-7","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;span&gt;AbstractSection&lt;/span&gt;\u0000 Background\u0000 &lt;p&gt;Targeted alpha therapy represents an advanced and rapidly evolving form of precision cancer treatment with increasing importance in recent years. The alpha-emitter &lt;sup&gt;225&lt;/sup&gt;Ac plays a key role in this clinical development due to its attractive physical and chemical properties. In this context, the macropa chelator has favorable characteristics in terms of labeling conditions and complex stability, making its derivatives exceptionally appealing for &lt;sup&gt;225&lt;/sup&gt;Ac-labeling of heat-sensitive biomolecules. However, preclinical evaluation of such &lt;sup&gt;225&lt;/sup&gt;Ac-containing molecules and comprehensive assessment of their pharmacokinetics, dosimetry and radiobiology necessitate a suitable diagnostic counterpart. Due to its attractive radiation properties, &lt;sup&gt;133&lt;/sup&gt;La represents an adequate positron-emitting radionuclide to form a matched pair with &lt;sup&gt;225&lt;/sup&gt;Ac for macropa-based radiopharmaceuticals. Herein, we describe the preparation and radiopharmacological characterization of macropa-functionalized, &lt;sup&gt;133&lt;/sup&gt;La/&lt;sup&gt;225&lt;/sup&gt;Ac-labeled single-domain antibodies (sdAbs) targeting the epidermal growth factor receptor (EGFR) to demonstrate the general suitability of this theranostic pair of radionuclides.&lt;/p&gt;\u0000 \u0000 &lt;span&gt;AbstractSection&lt;/span&gt;\u0000 Results\u0000 &lt;p&gt;The synthesis of a clickable, bicyclononyne-modified macropa chelator and its site-specific conjugation to azide-modified, monovalent and biparatopic sdAbs is presented. Subsequent labeling at room temperature (rt) for 15 min resulted in molar activities of 30 MBq/nmol for &lt;sup&gt;133&lt;/sup&gt;La and 0.5 MBq/nmol for &lt;sup&gt;225&lt;/sup&gt;Ac, respectively. In vitro studies using the &lt;sup&gt;133&lt;/sup&gt;La-labeled sdAbs revealed comparable binding characteristics, but an enhanced cellular internalization of the biparatopic variant compared to its monovalent counterparts. This increased uptake consequently resulted in higher cytotoxicity of the &lt;sup&gt;225&lt;/sup&gt;Ac-labeled biparatopic conjugate. In vivo PET imaging of the &lt;sup&gt;133&lt;/sup&gt;La-labeled conjugates indicated comparable uptake and retention of the mono- and biparatopic variants in liver and kidneys, with the former showing slightly higher tumor accumulation. Ex vivo biodistribution studies conducted with &lt;sup&gt;225&lt;/sup&gt;Ac-labeled conjugates largely confirmed the findings obtained by PET imaging, albeit with a marginally higher tumor accumulation of the biparatopic &lt;sup&gt;225&lt;/sup&gt;Ac-radioimmunoconjugate. Final histological examinations of tumor and kidney tissues showed DNA damage in the renal cortex of the &lt;sup&gt;225&lt;/sup&gt;Ac-radioimmunoconjugate-treated mice, but no differences in the number of γ-H2AX-positive cells in the corresponding tumor tissues could be detected.&lt;/p&gt;\u0000 \u0000 &lt;span&gt;AbstractSection&lt;/span&gt;\u0000 Conclusions\u0000 &lt;p&gt;We present a comp","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324001","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 of a toxin-selective immunotracer for in vivo detection of Clostridioides difficile infection by immunoPET","authors":"Mario González-Arjona,&nbsp;Lorena Cussó,&nbsp;Luis Alcalá,&nbsp;María Isabel González,&nbsp;Alexandra de Francisco,&nbsp;María Jesús Fernández-Aceñero,&nbsp;Dag Sehlin,&nbsp;Stina Syvänen,&nbsp;Emilio Bouza,&nbsp;Patricia Muñoz,&nbsp;Manuel Desco,&nbsp;Beatriz Salinas","doi":"10.1186/s41181-025-00350-x","DOIUrl":"10.1186/s41181-025-00350-x","url":null,"abstract":"<div><h3>Background</h3><p><i>Clostridioides difficile</i> infection (CDI) is a major healthcare challenge that is associated with high morbidity and mortality. Current diagnostic methods are limited in terms of specificity and invasiveness, necessitating novel, non-invasive imaging techniques. In this study, we develop and evaluate an immunoPET radiotracer targeting <i>C. difficile</i> toxin B for in vivo detection of CDI in a murine model.</p><h3>Results</h3><p>The monoclonal antibody bezlotoxumab, was radiolabeled with [¹²⁵I]I for in vitro characterization and with [⁸⁹Zr]Zr for in vivo PET imaging, resulting in high radiochemical yields (75.36 ± 4.11% for [¹²⁵I]I and 71.58 ± 8.19% for [⁸⁹Zr]Zr) and purities (&gt; 99.99% in both cases), with stable binding properties. PET/CT imaging 48 h post-infection in an animal model of CDI (C57BL/6 mice and ribotype 027 strain) demonstrated specific accumulation of [⁸⁹Zr]Zr-DFO-Beztxab in the colon and cecum of infected mice, thus making it possible to distinguish CDI from dysbiosis without specific <i>C. difficile</i> infection and healthy controls. Findings were confirmed by PET-based quantification and ex vivo biodistribution.</p><h3>Conclusions</h3><p>We successfully developed an immunoPET radiotracer targeting toxin B for detection of CDI. Its application in an animal CDI model proved its capacity to detect the source of infection with high specificity, while avoiding confusion with non-specific inflammation.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281875","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":"[90Y]Y-L4-Lipo/ ethyl esters of Iodized fatty acids of poppy seed oil (lipiodol® ultra-fluid), a new TARE formulation, designed from a lipophilic ligand for stability and safety","authors":"Olivier Fougère,&nbsp;Anne Dencausse,&nbsp;Nicolas Lepareur,&nbsp;Gaetan Van Simaeys,&nbsp;Gilles Doumont,&nbsp;Isabelle Gardin,&nbsp;Elisabeth Renard,&nbsp;Claire Hollenbeck,&nbsp;Coraline De Maeseneire,&nbsp;Nicolas Passon,&nbsp;Olivier Rousseaux,&nbsp;Sarah Catoen","doi":"10.1186/s41181-025-00352-9","DOIUrl":"10.1186/s41181-025-00352-9","url":null,"abstract":"<div><h3>Background</h3><p>Despite recent therapeutic advances, managing liver cancer remains a significant medical and economic priority for many countries. Patients often present at an advanced stage, preventing them from benefiting from salvage surgery. Consequently, palliative treatments play a crucial role in managing these cancers. Interventional radiology techniques are well-known for providing significant benefits to patients. [⁹⁰Y]Y-L4-Lipo/Lipiodol^® Ultra-Fluid is a novel transarterial radioembolization formulation designed for selective arterial injection to deliver localized radiation treatment of advanced unresectable liver tumors. This study aimed to confirm the stability of [⁹⁰Y]Y-L4-Lipo/Lipiodol^® Ultra-Fluid, investigate its biodistribution in an animal model, and conduct an initial dosimetry evaluation.</p><h3>Results</h3><p>Less than 3% of ⁹⁰Y was released from the [⁹⁰Y]Y-L4-Lipo/Lipiodol^® Ultra-Fluid formulation in human serum. The tumor-to-liver activity ratio (T/NT) expressed in %ID/g tissue at 1 h, 24 h, 3 days, and 6 days (5.50 ± 2.42, 3.28 ± 1.94, 4.89 ± 3.41 and 4.77 ± 1.59, respectively) suggests effective targeting of tumor tissue compared to healthy liver tissue. The extrapolated absorbed doses in Gy in humans to the tumor, normal liver, lung, and red marrow per GBq of [⁹⁰Y]Y-L4-Lipo/Lipiodol^® Ultra-Fluid administered were 54.3, 16.2, 0.69 and 0.89, for males, and 54.3, 22.3, 0.84 and 0.89, respectively, for females.</p><h3>Conclusion</h3><p>With good in vitro stability at low activity lasting at least 3 half-lives and a T/NT ratio of 4 in vivo, [⁹⁰Y]Y-L4-Lipo/Lipiodol^® Ultra-Fluid is confirmed as a valid candidate treatment for transarterial radioembolization of hepatocellular carcinoma. High activity stability in both in vitro and in vivo studies is needed to complete the formulation’s safety profile.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257034","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: Highlight selection of radiochemistry and radiopharmacy developments by editorial board","authors":"S. Spreckelmeyer,&nbsp;J. Dasilva,&nbsp;C. Decristoforo,&nbsp;R. H. Mach,&nbsp;J. Passchier,&nbsp;G. Carlucci,&nbsp;M. Al Qahtani,&nbsp;A. Duatti,&nbsp;B. T. Cornelissen,&nbsp;J. Engle,&nbsp;A. Denkova,&nbsp;J. J. M. A. Hendrikx,&nbsp;Y. Seimbille,&nbsp;X. Yang,&nbsp;H. Jia,&nbsp;M-R. Zhang,&nbsp;M. Yang,&nbsp;L. Perk,&nbsp;P. Caravan,&nbsp;P. Laverman,&nbsp;Z. Cheng,&nbsp;C. Hoehr,&nbsp;T. Sakr,&nbsp;J. R. Zeevaart","doi":"10.1186/s41181-025-00351-w","DOIUrl":"10.1186/s41181-025-00351-w","url":null,"abstract":"","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197959","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":"Selection of the optimal chelator for labeling of DARPin Ec1 with gallium-68 for PET imaging of EpCAM expression","authors":"Anzhelika Vorobyeva,&nbsp;Moeen-ud Din,&nbsp;Alexey Schulga,&nbsp;Elena Konovalova,&nbsp;Ayman Abouzayed,&nbsp;Olga Bragina,&nbsp;Ruonan Li,&nbsp;Torbjörn Gräslund,&nbsp;Sergey M. Deyev,&nbsp;Maryam Oroujeni","doi":"10.1186/s41181-025-00347-6","DOIUrl":"10.1186/s41181-025-00347-6","url":null,"abstract":"<div><h3>Background</h3><p>Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein, which is overexpressed in several types of malignancies. Designed ankyrin repeat protein (DARPin) Ec1 is a 19 kDa engineered scaffold protein that binds with high affinity to EpCAM. Radiolabelled Ec1 might be used as a companion diagnostic for the selection of patients for personalized therapy. This study aimed to investigate the influence of different radiometal-chelator complexes on the biodistribution and imaging contrast of ⁶⁸Ga-labelled Ec1. To investigate this, two macrocyclic chelators, 1,4,7-triazacyclononane-N,N,N-triacetic acid (NOTA) and 1-(1,3-carboxypropyl)-1,4,7-triazacyclononane-4,7-diacetic acid (NODAGA) were conjugated to the C-terminus of the Ec1. The previously developed DARPin Ec1 conjugated to 1,4,7,10-tetraazacylododecane-1,4,7,10-tetraacetic acid (DOTA) was used as a comparator.</p><h3>Results</h3><p>All Ec1 variants were successfully labelled with ⁶⁸Ga. The use of NOTA and NODAGA provided twice higher radiochemical yield and improved label stability compared to DOTA. All labelled Ec1 variants bound to the EpCAM-expressing cells with nanomolar affinity and preserved targeting specificity in vitro and in vivo. Biodistribution studies in mice bearing EpCAM-expressing SKOV-3 xenografts showed that [⁶⁸Ga]Ga-Ec1-NOTA had lower uptake in most normal organs while maintaining tumor uptake. Among all variants, [⁶⁸Ga]Ga-Ec1-NOTA showed the lowest liver uptake, with no significant differences in tumor uptake. Additionally, [⁶⁸Ga]Ga-Ec1-NOTA provided the highest tumor-to-blood ratio compared to [⁶⁸Ga]Ga-Ec1-DOTA and [⁶⁸Ga]Ga-Ec1-NODAGA.</p><h3>Conclusion</h3><p>[⁶⁸Ga]Ga-Ec1-NOTA is the preferred radioconjugate for PET imaging of EpCAM expression.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186174","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":"d-Glucose and its derivatives labeled with radioactive carbon and hydrogen: key tools for investigating biological processes and molecular mechanisms","authors":"Fahimeh Bayat","doi":"10.1186/s41181-025-00346-7","DOIUrl":"10.1186/s41181-025-00346-7","url":null,"abstract":"<div><h3>Background</h3><p>Radiolabeling is a technique that involves attaching radioactive isotopes to molecules, allowing for their tracking and analysis in biological systems. Radiolabeled <span>d</span>-glucose and its derivatives have a very prominent role in exploring metabolic pathways, the enzymatic system, and measuring the flow of the metabolites through biochemical reactions, as accumulation or deficiency of metabolites occurs along with metabolic disorders. Glucose as the main source of energy in the body is involved in different metabolic pathways like glycolysis, pentose phosphate pathway, and tricarboxylic acid cycle. Various derivatives of glucose are labeled at different positions by ¹⁴C and ³H. The aim of this review is to summarize some of the most significant aspects of the use of different radiolabeled <span>d</span>-glucose, 2-deoxy-<span>d</span>-glucose, and methyl-<i>α</i>-<span>d</span>-glucopyranoside.</p><h3>Main body</h3><p>This review focuses on the application of radiolabeled glucose derivatives in studying glucose transport systems, metabolic pathways, enzyme activity, and glucose utilization across various tissues. It highlights their role in understanding disease mechanisms in diabetes, cancer, heart failure, and metabolic disorders, and the impact of pharmacological agents and environmental pollutants.</p><h3>Conclusion</h3><p>In conclusion, radiolabeled glucose derivatives are invaluable tools for studying glucose metabolism across various tissues and organs. They provide critical insights into metabolic dysfunctions, disease mechanisms, and therapeutic interventions, aiding in the development of targeted treatments for conditions like diabetes, cancer, and cardiovascular diseases.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186173","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":"Preparation and preclinical evaluation of 18F-labeled folate-RGD peptide conjugate for PET imaging of triple-negative breast carcinoma","authors":"Subhani M. Okarvi,&nbsp;Yousef Maliki","doi":"10.1186/s41181-025-00349-4","DOIUrl":"10.1186/s41181-025-00349-4","url":null,"abstract":"<div><h3>Background</h3><p>Simultaneous targeting of RGD and FA receptors on breast carcinoma could improve the diagnostic outcome of breast cancer patients. In this study, we have designed and synthesized an FA-RGD heteromeric targeting vector, with both RGD and FA motifs, in one single molecule for positron emission tomography (PET) diagnostic imaging of breast carcinoma.</p><h3>Results</h3><p>Aoa-FA-RGD peptide conjugate was radiolabeled efficiently with [¹⁸F]FDG, resulting in high labeling efficiency (≥ 85%). The in vitro stability of the radiotracer in human plasma was found to be high. The Aoa-FA-RGD peptide conjugate showed the nanomolar affinity (≤ 51 nM) to the TNBC MDA-MB-231 cell line. In the MDA-MB-231 xenografts model, [¹⁸F]FDG-Aoa-FA-RGD peptide conjugate exhibited efficient clearance from the blood and excretion predominantly by the renal pathway (~ 56% ID), possibly due to its hydrophilic nature. A rapid accumulation of 3.30% ID/g in the TNBC MDA-MB-231 tumors was observed at 45 min p.i. Whereas a low accumulation of radioactivity was seen in the normal organs, including the heart, lungs, liver, stomach, spleen, intestines, and kidneys (&lt; 4% ID/g). The receptor specificity of the radiotracer was confirmed by the receptor-blocking assay. A rapid and efficient tumor targeting, together with the favorable pharmacokinetics, highlights the tumor-targeting potential of the radiofluroconjugate. Furthermore, PET imaging provided sufficient visualization of MDA-MB-231 tumors in mice.</p><h3>Conclusions</h3><p>Our findings suggest that the [¹⁸F]FDG-labeled FA-RGD peptide conjugate can be a useful agent for the efficient targeting of TNBC cells. This study suggests the potential of this innovative heteromeric targeting agent for rapid and efficient targeting of tumors and merits further advancement.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00349-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090973","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":"Toxicity study of TEoS-DAZA, a chemical precursor for functional liver imaging with PET/CT","authors":"Julia Greiser,&nbsp;Beatrice Engert,&nbsp;Roman Föll,&nbsp;Robert Klopfleisch,&nbsp;Rebecca Steens,&nbsp;Marion Hecht,&nbsp;Martin Freesmeyer","doi":"10.1186/s41181-025-00342-x","DOIUrl":"10.1186/s41181-025-00342-x","url":null,"abstract":"<div><h3>Background</h3><p><i>N</i>,1,4-Tri(4-ethoxy-2-hydroxybenzyl)-1,4-diazepan-6-amine (TEoS-DAZA), a novel radiopharmaceutical precursor for a liver-specific ⁶⁸Ga-based diagnostic radiopharmaceutical, was tested for toxicity in rats to ensure its safe applicability and to fulfil the preclinical requirements in preparation of a clinical study. The study was performed according to EMA draft Guideline on the non-clinical requirements for radiopharmaceuticals, as well as to the so-called microdosing approach of the ICH guideline M3 (R2).</p><h3>Results</h3><p>This randomized study was conducted using Wistar rats. The test item was administered intravenously at three different dose levels, the vehicle solution was administered to a separate group as control. Toxicity assessment included a 24 h observation period in three dose groups, and a 14-day recovery period in the high dose group. Animals were monitored regarding clinical behaviour, bodyweight, food and water consumption, additionally undergoing modified IRWIN, grip-strength and beam-walking tests. Following euthanisation, extensive haematological and clinical biochemical parameters were analysed. Necropsy and histopathology were performed. There was no evidence to any test-item related adversities at any dose level. No delayed effects were identified in any animal at the end of the recovery phase. Some small, albeit significant changes in haematology and clinical biochemistry could not be related to the test item administration. The NOAEL of TEoS-DAZA was determined at 1.4 mg/kg bodyweight.</p><h3>Conclusions</h3><p>Administration of a thousandfold clinical dose of TEoS-DAZA in rats did not cause any observable adverse events. An injectable solution of [⁶⁸Ga]Ga-TEoS-DAZA containing 100 µg of the precursor is safe for clinical application to humans from the pharmacological point of view. Subsequent dosimetry studies need to be undertaken to reveal any radiation related toxicity.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00342-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073555","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}