EJNMMI Radiopharmacy and Chemistry最新文献

{"title":"Stability assessment of PET radiopharmaceuticals under extreme conditions: an ICH-compliant study on radiochemical and enantiomeric purity","authors":"Viktória Forgács,&nbsp;Lívia Vonza,&nbsp;Adrienn Fekete,&nbsp;Gergely Farkasinszky,&nbsp;István Jószai","doi":"10.1186/s41181-025-00399-8","DOIUrl":"10.1186/s41181-025-00399-8","url":null,"abstract":"<div><h3>Background</h3><p>The stability testing of radiopharmaceuticals is a critical aspect of drug development and regulatory approval. The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) provides comprehensive guidelines for stability testing, as outlined in the ICH Harmonised Tripartite Guideline Q1A(R2). In this study, the stability of <i>o-</i>(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET) and methyl-[¹¹C]-L-methionine ([¹¹C]MET) was evaluated under GMP conditions to ensure their quality and safety. These radiopharmaceuticals are widely used in brain tumor imaging, yet their stability remains insufficiently studied. Given the short half-life of [¹¹C]MET (20 min), rapid preparation and administration are required, whereas the longer half-life of [¹⁸F]FET (110 min) allows for transportation, making stability considerations crucial due to potential environmental effects on the injection solution.</p><h3>Results</h3><p>Samples from each batch were tested at different temperatures and pH values across the entire expiration period. The radiochemical purity of [¹⁸F]FET remained between 98.04 and 100% by TLC, while UPLC values ranged from 95.93 to 99.59%. Differences between these methods stem from their sensitivity and operational principles. While UPLC provides precise separation, it may trap free fluoride, leading to overestimated purity values. In contrast, TLC allows for complete sample evaluation but has lower separation efficiency. Enantiomeric purity assessments confirmed that only the L-form was present, with no detectable D-enantiomer, in the case of [¹¹C]MET a maximum of 1.7% D-enantiomer was also detected. Stability remained above the 95% threshold between − 20 and 50 °C, with slight reductions at basic pH values. Even under stressed conditions no decomposition products were detected, and enantiomeric purity exceeded 90%, confirming the robustness of [¹⁸F]FET and [¹¹C]MET stability.</p><h3>Conclusion</h3><p>In this report, the stability of the [¹⁸F]FET and [¹¹C]MET radiopharmaceuticals was studied within the expiration time. [¹⁸F]FET remained stable until the end of the 12-h expiration time. [¹¹C]MET samples stored even under stressed conditions did not decrease under the acceptable limit during the shelf life of the radiopharmaceutical. These findings confirm that both radiopharmaceuticals maintain their stability within the defined shelf life, ensuring their reliability for clinical use. Further studies could explore additional environmental stress factors to enhance stability assessments and optimize storage conditions.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00399-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494009","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":"Nonclinical investigations of a novel heart-type fatty acid–binding protein ligand, [18F]LUF: three-lot process validation, safety assessment, and radiation dosimetry","authors":"Jun Toyohara,&nbsp;Masahiko Ito,&nbsp;Muneyuki Sakata,&nbsp;Tetsuro Tago,&nbsp;Taichi Komoda,&nbsp;Hiroshi Yoshino","doi":"10.1186/s41181-025-00404-0","DOIUrl":"10.1186/s41181-025-00404-0","url":null,"abstract":"<div><h3>Background</h3><p>Heart-type fatty acid–binding protein (FABP3) mediates the intracellular transport of fatty acids and is highly expressed in the myocardium. During myocardial infarction, FABP3 leaks from the myocardial cytoplasm into the blood; thus, detection of FABP3 using positron emission tomography (PET) is useful in identifying the site of myocardial damage. 4-(4-Fluoro-2-(1-phenyl-5-(2-(trifluoromethyl)phenyl)-1<i>H</i>-pyrazol-3-yl)phenoxy)butanoic acid (LUF) is a small-molecule organic compound that specifically binds FABP3. We confirmed that fluorine-18–labeled LUF enables clear, high-quality visualization of the myocardium as well as lesions associated with myocardial injury. In this study, we performed a process validation of [¹⁸F]LUF production for clinical use and evaluated its nonclinical toxicity and radiation dosimetry estimates using mouse biodistribution data.</p><h3>Results</h3><p>The activity yield of [¹⁸F]LUF at the end of synthesis was &gt; 8 GBq, with &gt; 99% radiochemical purity, &gt; 500 GBq/μmol molar activity, and &lt; 1.5 μg/185 MBq total chemical content. All process validation batches complied with the product specifications. An extended single-dose intravenous toxicity study in male and female Sprague–Dawley rats indicated a no-observed adverse effect level for LUF and decay-outed [¹⁸F]LUF injection solution of ≥ 25 μg/kg and ≥ 2.5 mL/kg, respectively. These doses are &gt; 100 times the postulated maximum dose of LUF (0.25 μg/kg) and [¹⁸F]LUF injection solution (370 MBq). Reverse mutation tests were negative for LUF and the OH form produced after β-decay of [¹⁸F]LUF. Neither LUF nor the OH form exhibited cardiotoxicity toward cardiomyocytes derived from human induced pluripotent stem cells at &gt; 100 times the postulated maximum dose. Biodistribution study results demonstrated predominantly hepatobiliary excretion of radioactivity. The most critical organ affected was the heart wall (68.6 μGy/MBq). The estimated effective dose was calculated as 10.2 μSv/MBq. These radiation exposure doses are equivalent to 25.4 mGy (heart wall) and 3.78 mSv for a planned maximum dose of 370 MBq.</p><h3>Conclusions</h3><p>[¹⁸F]LUF shows acceptable pharmacological safety at the dose required for adequate PET imaging. The potential risks associated with [¹⁸F]LUF injection are well within the acceptable dose limits.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00404-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145487271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and in vitro characterization of [198Au]Auranofin","authors":"Punita Bhardwaj,&nbsp;Caroline Frohner,&nbsp;Christopher Geppert,&nbsp;Christian Gorges,&nbsp;Winfried Brenner,&nbsp;Guilhem Claude,&nbsp;Sarah Spreckelmeyer","doi":"10.1186/s41181-025-00401-3","DOIUrl":"10.1186/s41181-025-00401-3","url":null,"abstract":"<div><h3>Background</h3><p>Radiopharmaceuticals offer targeted treatment by combining diagnostic or therapeutic radionuclides with biologically active molecules. Auranofin is the only Food and Drug Administration (FDA) approved gold(I) complex, originally developed for the treatment of rheumatoid arthritis. Recent evidence has highlighted its potential as an anticancer agent due to its ability to disrupt redox signaling, inhibit thioredoxin reductase, and impair glycolytic metabolism. This study aims to incorporate the true theranostic radionuclide ¹⁹⁸Au into the Auranofin scaffold and evaluate its impact in-vitro on cancer cells.</p><h3>Results</h3><p>Carrier-added (c.a.)¹⁹⁸Au was produced via neutron activation of ¹⁹⁷Au and subsequently converted into c.a. H [¹⁹⁸Au] [AuCl₄]. Downscaled synthetic protocols were developed to sequentially generate c.a. [¹⁹⁸Au] [Au(tht)Cl], [¹⁹⁸Au] [Au(PEt₃)Cl], and [¹⁹⁸Au]Auranofin. Radiochemical purity was evaluated using radio-high performance liquid chromatography, and in vitro stability was assessed in human serum albumin (HSA) over 72 h. Cytotoxic and metabolic activity were investigated in MCF7 and PC3 cancer cell lines using the cell viability assay 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) and hexokinase assay, respectively. [¹⁹⁸Au]Auranofin (c.a.) was obtained with a yield of 57.0 ± 3.2% and a radiochemical purity of 96.2 ± 3.9%. The compound demonstrated stability in human serum albumin, maintaining 96.9 ± 2.5% integrity over 72 h. In vitro studies revealed that c.a. [¹⁹⁸Au]Auranofin exhibited enhanced cytotoxicity and significant hexokinase inhibition compared to its non-radioactive counterpart, while the precursor complexes remained non-toxic up to 20 µM. Viability loss was both concentration and radioactivity dependent across both cell lines.</p><h3>Conclusions</h3><p>[¹⁹⁸Au]Auranofin (c.a.) represents a stable and effective radiogold-based radiopharmaceutical agent, offering redox-targeted cytotoxicity alongside β⁻ emission mediated cell death and γ emission based imaging potential. These findings highlight c.a. [¹⁹⁸Au]Auranofin as a promising radiogold-based theranostic candidate, offering dual capabilities in targeted cytotoxicity and nuclear imaging. While the in vitro results are encouraging, further in vivo and translational studies are warranted to fully evaluate its clinical potential in nuclear medicine guided cancer therapy.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00401-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443647","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]Fentanyl: radiosynthesis and preclinical pet imaging for its pharmacokinetics","authors":"Woochan Kim,&nbsp;Aaron K. Wozniak,&nbsp;Nathaniel J. Burkard,&nbsp;Michael L. Freaney,&nbsp;Ailen Costamagna-Soto,&nbsp;Kelly A. O’Conor,&nbsp;Abolghasem Bakhoda,&nbsp;Seth M. Eisenberg,&nbsp;Wenjing Zhao,&nbsp;Jeih-San Liow,&nbsp;Nora D. Volkow,&nbsp;Sung Won Kim","doi":"10.1186/s41181-025-00394-z","DOIUrl":"10.1186/s41181-025-00394-z","url":null,"abstract":"<div><h3>Background</h3><p>Fentanyl is a potent synthetic opioid widely used for pain management and anesthesia, but the high prevalence of its misuse and its key contribution to overdose fatalities in the United States have made it a major drug of concern. Although fentanyl’s onset, duration, and toxicity depend on its pharmacokinetics and specific tissue distribution, most studies have focused primarily on plasma concentrations, leaving its distribution in critical tissues largely unexplored (this knowledge gap limits our understanding of fentanyl’s clinical effects, tissue accumulation, and the factors influencing its efficacy and safety). Here, we report the radiosynthesis of [¹¹C]fentanyl for PET imaging and present a preliminary whole-body pharmacokinetic study in rodents.</p><h3>Results</h3><p>[¹¹C]Fentanyl was synthesized in 42 min in a high radiochemical yield (10.4 ± 5.7%, n = 5), radiochemical purity (&gt; 99%), and molar activity (up to 2571.5 GBq/µmol at EOB). <i>N</i>,<i>N</i>-Diisopropylethylamine in chloroform was optimal for amidation. PET imaging in rats revealed rapid brain uptake (SUV_max 2.71 ± 1.04 g/mL) and fast washout (T_1/2 = 5.06 min), both significantly increased by efflux transporter inhibition or knockout. Peripherally, high and prolonged uptake in adipose tissues was observed (SUV_max = 1.73 ± 0.313 g/mL, T_1/2 = 177 min), with &gt; 60% of C-11 remaining as unchanged [¹¹C]fentanyl at 60 min.</p><h3>Conclusions</h3><p>We successfully developed and automated the radiosynthesis of [¹¹C]fentanyl, enabling PET imaging that revealed rapid brain kinetics and a critical role of P-gp/BCRP efflux in fentanyl disposition in brain. Prolonged retention in adipose tissue may delay brain clearance, potentially increasing the risk of re-narcotization (as has been reported in clinical cases after naloxone reversal). These findings advance our ability to quantify fentanyl tissue distribution and pharmacokinetics in the brain and body and provide a valuable tool for further studies in preclinical and clinical settings.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00394-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385647","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":"Automated radiosynthesis of [18F]fluoromannitol for clinical research on a commercially available trasis allinone radiosynthesizer","authors":"Amy L. Vāvere,&nbsp;Allison J. Clay,&nbsp;Arijit Ghosh,&nbsp;Joana Marie Almazan,&nbsp;Melissa J. Brown,&nbsp;Spenser Simpson,&nbsp;Kiel D. Neumann","doi":"10.1186/s41181-025-00388-x","DOIUrl":"10.1186/s41181-025-00388-x","url":null,"abstract":"<div><h3>Background</h3><p>Infections pose a significant risk to immunocompromised individuals, and accurate, efficient diagnosis remain challenging. Current imaging methods like MRI and FDG PET lack pathogen specificity which complicate diagnosis and lead to overuse of antibiotics. Recent data shows that [¹⁸F]fluoromannitol ([¹⁸F]FMtl) is sensitive and specific to infection in vivo by exploiting the pathogen-specific mannitol transporter. This work aims to establish a reliable, automated method for producing [¹⁸F]fluoromannitol to facilitate clinical research studies in human subjects.</p><h3>Results</h3><p>This study optimized and automated the radiosynthesis of [¹⁸F]fluoromannitol ([¹⁸F]FMtl) on a Trasis AllinOne synthesizer. The 105-minute synthesis achieved an average yield of 11.0% (<i>n</i> = 19) with &gt; 97% radiochemical purity, and the product remained stable for at least 8 h. While yield was lower than the previously reported manual method, automation enabled reproducibility and sterility. Process improvements included optimizing evaporation steps and reaction temperature, which significantly increased fluorine incorporation and yield. The process was validated to meet USP &lt; 823 &gt; regulatory requirements including full QC testing on three consecutive batches.</p><h3>Conclusions</h3><p>An automated method for the radiochemical synthesis of [¹⁸F]fluoromannitol was developed and optimized on a commercially available Trasis AllinOne radiosynthesizer. This method allows for the reliable production and global dissemination of [¹⁸F]FMtl for use in clinical research trials.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00388-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385604","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":"Establishment and validation of an alternative automated synthesis of [68Ga]Ga-DOTA-Siglec-9 in an independent laboratory for clinical use","authors":"Silvia Migliari,&nbsp;Alessandra Guercio,&nbsp;Anna Gagliardi,&nbsp;Roberta Giaccari,&nbsp;Stefano Bruno,&nbsp;Anne Roivainen,&nbsp;Sarita Forsback,&nbsp;Giorgio Baldari,&nbsp;Maura Scarlattei,&nbsp;Livia Ruffini","doi":"10.1186/s41181-025-00396-x","DOIUrl":"10.1186/s41181-025-00396-x","url":null,"abstract":"<div><h3>Background</h3><p>Siglec-9, a member of the Siglec family of receptors, plays a crucial role in modulating immune cell trafficking and inflammation, with significant clinical implications. It is predominantly expressed on immune cells such as neutrophils, monocytes, and dendritic cells –key components of both innate and adaptive immunity. Siglec-9 binds to sialic acid residues on glycoproteins, commonly found on endothelial cells, a mechanism central to immune regulation during inflammation and tissue injury. Notably, its interaction with vascular adhesion protein 1 (VAP-1), an endothelial adhesion molecule, is of particular interest for therapeutic development in chronic inflammatory diseases, autoimmune disorders, and cancer. Recent studies have demonstrated that a Siglec-9 motif-containing peptide conjugated with 1,4,7,10-tetraazacyclododecane-N, N′,N′′,N′′′-tetraacetic acid (DOTA) and radiolabelled with gallium-68 ([⁶⁸Ga]Ga-DOTA-Siglec-9) enables effective positron emission tomography (PET) imaging of these pathological conditions. This study aimed to develop a new automated radiolabelling protocol for the preparation of [⁶⁸Ga]Ga-DOTA-Siglec-9 for clinical use. The synthesis was carried out using a fully automated module with real-time monitoring of key parameters including time, temperature, and radioactivity.</p><h3>Results</h3><p>Following optimization of labelling conditions and assessment of peptide stability, [⁶⁸Ga]Ga-DOTA-Siglec-9 was successfully synthesized with a radiochemical yield (RY) of 55.04%, radiochemical purity (RCP) of 99.48%, and molar activity (Am) of 23.15 GBq/µmol at 65 °C in 6 min. Process validation yielded consistent mean values of RY (56.16%), RCP (99.40%). and Am (20.26 GBq/µmol). Stability testing at room temperature over 3 h demonstrated that [⁶⁸Ga]Ga-DOTA-Siglec-9 maintained acceptable RCP (mean99.29%), pH, appearance, and sterility.</p><h3>Conclusion</h3><p>The final product meets <i>Ph. Eur.</i> quality requirements and is suitable for clinical application.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00396-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145316418","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":"Quantitative dual-isotope preclinical SPECT/CT imaging and biodistribution of the mercury-197m/g theranostic pair with [197m/gHg]HgCl2 and a [197m/gHg]Hg-tetrathiol complex as a platform for radiopharmaceutical development","authors":"Parmissa Randhawa,&nbsp;Cristina Rodríguez-Rodríguez,&nbsp;Helena Koniar,&nbsp;Patrick R. W. J. Davey,&nbsp;Shaohuang Chen,&nbsp;Valery Radchenko,&nbsp;Caterina F. Ramogida","doi":"10.1186/s41181-025-00391-2","DOIUrl":"10.1186/s41181-025-00391-2","url":null,"abstract":"<div><h3>Background</h3><p>Mercury-197m (^197mHg, t_1/2 = 23.8 h) and mercury-197g (^197gHg, t_1/2 = 64.14 h) possess favorable nuclear properties for imaging and targeted therapy, but the development of suitable chelators for mercury-based radiopharmaceuticals remains underexplored. Additionally, accurate imaging and quantification of mercury isotopes, particularly in dual-isotope formats, require tools that account for their complex decay schemes. Phantom imaging studies are essential for validating spatial resolution, quantitative accuracy, and isotope-specific calibration prior to in vivo application. In this study, we investigated the commercially available ligand H₄Tetrathiol for chelation of [^197m/gHg]Hg²⁺ and developed a robust imaging and quantification pipeline to support the use of these nuclear isomers in preclinical imaging.</p><h3>Results</h3><p>Radiolabeling of H₄Tetrathiol yielded exceptionally efficient complexation, achieving the lowest ligand-to-metal ratio reported for radio-mercury. The resulting [^197m/gHg]Hg²⁺-complex demonstrated high in vitro stability in the presence of serum proteins, glutathione, and competing biologically relevant metal ions, though it exhibited kinetic lability when challenged with excess HgCl₂. In vivo biodistribution studies in mice showed a distinct pharmacokinetic profile from unchelated [^197m/gHg]HgCl₂, suggesting in vivo complex stability. Phantom imaging studies with a high sensitivity collimator demonstrated submillimeter resolution (≥ 1.1 mm) for both ^197gHg and ^197mHg, with decay behavior consistent with known half-lives. To facilitate accurate quantification, we developed <i>HgQuant</i>, a Python-based tool for isotope-specific calibration, Bateman decay correction, and automated dual-isotope analysis. This tool enabled reproducible, time-resolved quantification in both phantom and in vivo settings.</p><h3>Conclusions</h3><p>These results establish Tetrathiol as a promising scaffold for mercury-based theranostics, offering efficient radiolabeling and in vivo stability. The integration of high-resolution imaging and <i>HgQuant</i>-based quantification of each isomer establishes a comprehensive framework for advancing [^197m/gHg]Hg radiopharmaceutical development.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12521730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285048","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":"PET imaging of mitochondrial complex-I in the adenine-induced tubulointerstitial nephropathy mouse model using [18F]BCPP-BF","authors":"Kenneth Dahl,&nbsp;Peter Johnström,&nbsp;Miklós Toth,&nbsp;Vasco C. Sousa,&nbsp;Charlotte Ericsson,&nbsp;Maria Strömstedt,&nbsp;Tord Inghardt,&nbsp;Miguel A. Cortés González,&nbsp;Anna Reznichenko,&nbsp;Aurelija Jucaite,&nbsp;Zsolt Cselényi,&nbsp;Robert Unwin,&nbsp;Hiroyuki Ohba,&nbsp;Christer Halldin,&nbsp;Benjamin Challis,&nbsp;Hideo Tsukada,&nbsp;Magnus Schou","doi":"10.1186/s41181-025-00392-1","DOIUrl":"10.1186/s41181-025-00392-1","url":null,"abstract":"<div><h3>Background</h3><p>Chronic kidney disease (CKD) poses a significant global health burden with limited effective treatments for its prevention, progression, and associated complications. Mitochondrial dysfunction is recognized as a pivotal factor in the development of kidney diseases, with mitochondrial complex-I (MC-I) playing a crucial role in assessing overall mitochondrial function. Recent advancements in selective MC-I positron emission tomography (PET) radioligands now allow for non-invasive visualization and quantification of renal mitochondrial status in vivo. The aim of the present study was to evaluate the utility of [¹⁸F]BCPP-BF in the adenine induced tubulointerstitial nephropathy model.</p><h3>Results</h3><p>Binding of the MC-I targeted PET radioligand, [¹⁸F]BCPP-BF, showed a gradual decline in the kidneys of mice on an adenine-rich diet. [¹⁸F]BCPP-BF binding decreased by 59–61% compared to baseline after two weeks of adenine treatment. These results of reduced uptake were further confirmed by in vitro autoradiography. In kidneys from adenine-fed mice, [¹⁸F]BCPP-BF specific binding was reduced by 65.6% compared to control kidney sections.</p><h3>Conclusions</h3><p>Altogether, the findings suggest that [¹⁸F]BCPP-BF holds potential as an imaging biomarker for renal failure. However, further preclinical studies and validation in human subjects are necessary before it can be established as a reliable indicator for the progression of CKD.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12518723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278624","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":"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}