EJNMMI Radiopharmacy and Chemistry最新文献

{"title":"Impact of prolonged use of NSAID (Diclofenac) on 99mTc-MAG3 and 99mTc-DTPA renography","authors":"Seham Mustafa,&nbsp;Abdelhamid Elgazzar","doi":"10.1186/s41181-024-00325-4","DOIUrl":"10.1186/s41181-024-00325-4","url":null,"abstract":"<div><h3>Background</h3><p>Non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, are globally recognized as the primary choice for alleviating kidney pain and ureteric colic. This study examines the effects of long-term diclofenac administration on renography using two radiopharmaceuticals: 99mTc-mercaptoacetyltriglycine (99mTc-MAG3), which is excreted almost exclusively by the renal tubules, and 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA), which is predominantly excreted by glomerular filtration.</p><h3>Results</h3><p>Diclofenac administration caused a rightward shift in renograms, indicating delayed renal uptake and clearance for both tracers. For 99mTc-MAG3, the average time to peak activity (Tmax) increased from 2.88 ± 0.3 min (control) to 4.2 ± 0.3 min (treated), while time from peak to 50% activity (T½) rose from 4.16 ± 0.1 min to 5.48 ± 0.5 min. For 99mTc-DTPA, Tmax increased from 4.3 ± 0.4 min to 12.9 ± 2.0 min, and T½ extended from 13.35 ± 1.5 min to 29.75 ± 2.0 min (<i>n</i> = 12; *<i>p</i> &lt; 0.05 for all comparisons). Delayed tracer arrival in the bladder was particularly pronounced with 99mTc-DTPA.</p><h3>Conclusions</h3><p>Chronic diclofenac exposure significantly delays Tmax and T½ for both tracers, with a greater impact observed using 99mTc-DTPA. These findings highlight 99mTc-MAG3 as the preferred radiopharmaceutical for renography in settings involving long-term NSAID administration, ensuring accurate and reliable interpretation and minimizing variability associated with radiopharmaceutical selection.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00325-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143740784","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 preclinical evaluation of gastrin releasing peptide receptor antagonist [18F]MeTz-PEG2-RM26 for positron emission tomography","authors":"Panagiotis Kanellopoulos,&nbsp;Fanny Lundmark,&nbsp;Ayman Abouzayed,&nbsp;Lorenzo Jacopo Ilic Balestri,&nbsp;Esther Olaniran Håkansson,&nbsp;Karim Obeid,&nbsp;Luke R. Odell,&nbsp;Vladimir Tolmachev,&nbsp;Ulrika Rosenström,&nbsp;Jonas Eriksson,&nbsp;Anna Orlova","doi":"10.1186/s41181-025-00336-9","DOIUrl":"10.1186/s41181-025-00336-9","url":null,"abstract":"<div><h3>Background</h3><p>The gastrin-releasing peptide receptor (GRPR) is overexpressed in the majority of primary prostate cancer lesions, with persistent expression in lymph nodes and bone metastases, making it a legitimate molecular target for diagnostic imaging and staging. This study presents the synthesis and preclinical evaluation of [¹⁸F]MeTz-PEG₂-RM26, a GRPR antagonist which utilises the Inverse Electron Demand Diels-Alder (IEDDA) reaction for ¹⁸F-labelling. This click-chemistry approach allows for site-specific incorporation of fluorine-18 under mild conditions, preserving the peptide’s structural integrity and biological activity. Receptor specificity and affinity of [¹⁸F]MeTz-PEG₂-RM26 were evaluated in vitro using GRPR-expressing PC-3 cells. Furthermore, the biodistribution profile of [¹⁸F]MeTz-PEG₂-RM26 was assessed in NMRI mice and its tumour-targeting capability was investigated in mice bearing PC-3 xenografts.</p><h3>Results</h3><p>The labelling of TCO-PEG₂-RM26 precursor involved three steps: (1) synthesis of an ¹⁸F-labelled activated ester on a quaternary methyl ammonium (QMA) cartridge, (2) conjugation of the labelled ester to a tetrazine amine, and (3) attachment to TCO-PEG₂-RM26 via an IEDDA click reaction. This production method of [¹⁸F]MeTz-PEG₂-RM26 afforded a high apparent molar activity of 3.5–4.3 GBq/µmol and radiochemical purity exceeding 98%, with 43–70 MBq activity incorporation, while the entire synthesis was completed within 75 min. Both in vitro and in vivo studies confirmed the specific binding of [¹⁸F]MeTz-PEG₂-RM26 to GRPR, with a significant reduction in activity uptake observed upon receptor saturation. The radioligand exhibited rapid blood clearance and minimal bone uptake, confirming the stability of the fluorine-carbon bond. However, high hepatic uptake (12–13% IA/g at 1 h post-injection) indicated predominant hepatobiliary excretion. Receptor-mediated uptake was observed in the tumours and pancreatic tissue, although the overall activity uptake in tumours was low, likely due to the rapid hepatobiliary clearance of [¹⁸F]MeTz-PEG₂-RM26.</p><h3>Conclusions</h3><p>These findings demonstrate the effectiveness of the IEDDA click reaction for fluorine-18 labelling of GRPR-targeting PET tracers. Future studies should focus on increasing the hydrophilicity of the imaging probe to improve the targeting properties and biodistribution profile of the radioligand.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00336-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698450","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":"S. Spreckelmeyer,&nbsp;J. Dasilva,&nbsp;C. Decristoforo,&nbsp;R. H. Mach,&nbsp;J. Passchier,&nbsp;G. Carlucci,&nbsp;M. Al Qhatani,&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/s41181-025-00335-w","DOIUrl":"10.1186/s41181-025-00335-w","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 24 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":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00335-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698580","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":"Hematological toxicity of [225Ac]Ac-PSMA-617 and [177Lu]Lu-PSMA-617 in RM1-PGLS syngeneic mouse model","authors":"Meryl Maria Vilangattil,&nbsp;Abir Swaidan,&nbsp;Jonathan Godinez,&nbsp;Marco F. Taddio,&nbsp;Johannes Czernin,&nbsp;Christine E. Mona,&nbsp;Giuseppe Carlucci","doi":"10.1186/s41181-025-00333-y","DOIUrl":"10.1186/s41181-025-00333-y","url":null,"abstract":"<div><h3>Background</h3><p>Prostate cancer (PC) has a 34% 5-year survival rate after progressing to metastatic castration-resistant prostate cancer (mCRPC), which occurs in 20–30% of cases. Treatments like chemotherapy, immunotherapy, and PSMA-targeted radioligand therapy (RLT) show promise, but challenges remain with tumor resistance, side effects, and dose-limiting toxicity in kidneys and bone marrow. This study investigated the hematotoxicity, treatment efficacy, and recovery after [¹⁷⁷Lu]Lu-PSMA-617 and [²²⁵Ac]Ac-PSMA-617 treatment in a syngeneic PC mouse model.</p><h3>Method</h3><p>Twenty-five male C57BL/6 mice were inoculated with RM1-PGLS cells and monitored using [⁶⁸Ga]Ga-PSMA-11 PET/CT. The mice were divided into five groups as follows: (1) [²²⁵Ac]Ac-PSMA-617 treatment with tumors, (2) [¹⁷⁷Lu]Lu-PSMA-617 treatment with tumors, (3) control group with tumors, (4) [²²⁵Ac]Ac-PSMA-617 treatment without tumors, and (5) [¹⁷⁷Lu]Lu-PSMA-617 treatment without tumors. Tumor volume was measured weekly, and animals were sacrificed when tumors reached 1.5 cm³. Endpoint criteria included tumor size, survival, and body mass. Blood samples were collected at different time points to assess blood cell counts and liver and kidney function.</p><h3>Results</h3><p>Both treatments significantly slowed tumor progression and extended survival. [²²⁵Ac]Ac-PSMA-617-treated mice had a median survival of 70 days, compared to 58 days for [¹⁷⁷Lu]Lu-PSMA-617-treated mice and 30 days for the control group. Tumor volumes were significantly reduced in both treatment groups (<i>P</i> &lt; 0.05). Hematological analysis showed that both treatments reduced WBCs, RBCs, and platelets, but values normalized within 35–42 days. Liver and kidney functions remained unaffected, and no significant renal or hepatic toxicity was observed.</p><h3>Conclusion</h3><p>Both [²²⁵Ac]Ac-PSMA-617 and [¹⁷⁷Lu]Lu-PSMA-617 caused transient hematotoxicity without prolonged effects. The data do not explicitly support the necessity of immunocompetent models for studying therapeutic outcomes in this context. Future studies incorporating immune profiling are warranted to investigate immune system interactions in radioligand therapy further.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00333-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143688270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-efficiency [18F]fluoride pre-concentration using a laser-micromachined anion-exchange micro-cartridge","authors":"Antonio Arleques Gomes,&nbsp;Arian Pérez Nario,&nbsp;André Luis Lapolli,&nbsp;Ricardo Elgul Samad,&nbsp;Emerson Soares Bernardes,&nbsp;Wagner de Rossi","doi":"10.1186/s41181-025-00334-x","DOIUrl":"10.1186/s41181-025-00334-x","url":null,"abstract":"<div><h3>Background</h3><p>The use of radiopharmaceuticals labelled with fluorine-18 in non-invasive imaging, particularly in Positron Emission Tomography (PET), increased significantly during the last decade. However, traditional nucleophilic fluorination synthesis methods in most cases require azeotropic drying steps, leading to loss of activity and increased synthesis time. Microfluidic devices offer improvements with shorter reaction times, higher elution efficiency, and reduced reagent quantities.</p><h3>Results</h3><p>We developed a novel micro-cartridge for [¹⁸F]fluoride trapping and elution, etched in borosilicate optical glass (BK7) using ultrashort laser pulse machining. The micro-cartridge has a bead volume of 17 µL and a maximum capacity of 8.5 mg for anion exchange resin. The micro-cartridge, without the need for QMA preconditioning, exhibited an overall trapping efficiency and recovery efficiency (RE) of (94.09 ± 0.12)% using an activity exceeding 123 GBq of [¹⁸F]fluoride. This RE was obtained using 100 µL of a standard solution of anhydrous acetonitrile with Kryptofix 2.2.2, containing only 5 µL of water and 5.4 µmol of K₂CO₃ for [¹⁸F]fluoride elution. This solution was employed directly in the radiosynthesis of [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO), resulting in a 100% radiochemical conversion (RCC) to THP-protected [¹⁸F]FMISO within 10 min at 110 °C.</p><h3>Conclusions</h3><p>The developed micro-cartridge provides a novel tool for integrating microfluidic chips into conventional cassettes, facilitating more efficient radiopharmaceutical preparation.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00334-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and evaluation of Hsp90-targeting nanobodies for visualisation of extracellular Hsp90 in tumours using PET imaging","authors":"Valeria Narykina,&nbsp;Janke Kleynhans,&nbsp;Christopher Cawthorne,&nbsp;Joost Schymkowitz,&nbsp;Frederic Rousseau,&nbsp;Guy Bormans","doi":"10.1186/s41181-025-00331-0","DOIUrl":"10.1186/s41181-025-00331-0","url":null,"abstract":"<div><h3>Background</h3><p>The extracellular localisation of the Heat shock protein 90 (Hsp90) is associated with the diseased state and wound healing and presents a promising opportunity for cancer targeting using Positron Emission Tomography (PET) imaging and molecularly targeted radiotherapy. The aim of this work is to develop a radiotracer with low nanomolar binding affinity to target the extracellular and particularly membrane pool of Hsp90, evaluate it in vitro, and conduct preliminary PET studies in vivo in mouse tumour models. Variable Heavy domain of Heavy chain antibodies, often referred to as Nanobodies, are suitable targeting vectors for the extracellular targets due to their favourable pharmacokinetic properties and low nanomolar target affinities. The main objective of the study is to target tumours expressing extracellular and membrane Hsp90 phenotype with minimal tracer accumulation in the non-target organs, which limited the translation of previously studied small molecule cytosolic Hsp90 tracers suffering from high non-Hsp90 specific background in the abdominal area.</p><h3>Results</h3><p>Six nanobodies were obtained after llama immunization with recombinant Hsp90α and ELISA biopanning, produced in <i>E. coli</i> and screened for stability and affinity. We selected one nanobody, 4DAM26, with good thermal stability, no aggregation at elevated temperatures, and low nanomolar affinity towards Hsp90α and Hsp90β isoforms for translation as a PET radiotracer. The nanobody was bioconjugated to <i>p</i>-NCS-NODAGA and radiolabeled with gallium-68 with 75 ± 11% radiochemical yield and &gt; 99% radiochemical purity and remained stable up to 3 h in phosphate buffered saline and mouse serum. Pilot in vivo evaluation using µPET/CT and ex vivo biodistribution demonstrated a favourable pharmacokinetic profile, but the tumour uptake was non-distinguishable from the background tissue.</p><h3>Conclusion</h3><p>Compared to the small molecule Hsp90 tracers, the studied Nb-based tracer has improved pharmacokinetics properties including renal clearance and almost no accumulation in the non-target organs. Tumour uptake, on the other hand, was minimal and could not be differentiated from the background in µPET/CT. Our experiments indicate that in the studied models, membrane and extracellular expression of Hsp90 is majorly an artifact of cellular death, as only dead/dying cells had accessible pools of Hsp90 by flow cytometry, a consequence of a leaky membrane. More fundamental research is required to reassess the role of extracellular Hsp90 in cancer, and our future efforts will be focused on improving our inventory of cytosolic Hsp90 tracers with proven Hsp90-specific tumour accumulation.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00331-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466053","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":"Ac-225 radiochemistry through the lens of [225Ac]Ac-DOTA-TATE","authors":"Eline L. Hooijman,&nbsp;Jan R. de Jong,&nbsp;Carolline M. Ntihabose,&nbsp;Frank Bruchertseifer,&nbsp;Alfred Morgenstern,&nbsp;Yann Seimbille,&nbsp;Tessa Brabander,&nbsp;Stijn L. W. Koolen,&nbsp;Erik de Blois","doi":"10.1186/s41181-025-00332-z","DOIUrl":"10.1186/s41181-025-00332-z","url":null,"abstract":"<div><h3>Background</h3><p>Targeted alpha therapy with Ac-225 showed to be effective in treating metastatic cancers. However, the complex decay chain requires optimized radiolabeling and quality control. This study aims to determine critical parameters and establish optimal labeling and accurate measuring techniques for radiochemical yield and purity with DOTA-TATE as a model molecule. Ac-225 sources were analyzed for metals (ΣFe, Zn, Cu) and quantified by UPLC. Optimization of radiolabeling kinetics for clinical conditions was performed in regards to temperature (20–90 °C), heating time (5–60 min), pH (2.5–10, with/without excess of metal ions), buffers, quenchers, volume (0.1–10 mL) and molar activity (90–540 kBq/nmol). The quality control was investigated using radio-TLC/HPLC by changing gradient to evaluate peak separation, radiolysed peptide and impurity separation.</p><h3>Results</h3><p>Metal ingrowth was observed in Ac-225 stocks (<i>n</i> = 3), (time of arrival: 17.9, 36.8 and 101.4 nmol per 10 MBq). Optimal radiochemical yields were achieved with &gt; 80 °C (20 min) at pH 8.5 (15 mM TRIS) up to 270 kBq. Labeling at a high pH showed a higher RCY, even in presence of an excess of metals. High stability (RCP &gt; 90%) was achieved after addition of quenchers (cysteine, methionine, ascorbate, histidine, or gentisic acid (35 mM)) up to 24 h. For optimal determination of the radiochemical purity (indirect HPLC) fifty fractions are required.</p><h3>Conclusion</h3><p>The quality of Ac-225 labeled DOTA-radiopharmaceuticals is highly dependent on the pH and stabilization (buffer/quencher). Within this research it is demonstrated that optimized quality control methods and accurate measurement of the radiolabeling kinetics are crucial to ensure safe implementation for patient treatment.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00332-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455413","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 an automated method for in-house production of sodium 18F-fluoride for injection: process validation as a step toward routine clinical application","authors":"Marija Atanasova Lazareva,&nbsp;Maja Chochevska,&nbsp;Katerina Kolevska,&nbsp;Maja Velickovska,&nbsp;Filip Jolevski,&nbsp;Paulina Apostolova,&nbsp;Ana Ugrinska,&nbsp;Emilija Janevik-Ivanovska","doi":"10.1186/s41181-025-00329-8","DOIUrl":"10.1186/s41181-025-00329-8","url":null,"abstract":"<div><h3>Background</h3><p>Sodium ¹⁸F-fluoride for injection can be easily cyclotron-produced and purified, as a simple inorganic salt, by adsorption/desorption onto an anion-exchange cartridge and then dispensed for clinical use. Since the clinical demand for this radiopharmaceutical is constantly increasing, this study aimed to design and develop a simple, fully automated method for the in-house, rapid, and efficient processing and dispensing of injectable solutions of Sodium ¹⁸F-fluoride without the need of a synthesis module and disposable kit, but using only the dispensing unit.</p><h3>Results</h3><p>A new simple method for the efficient routine production of injectable solutions of [¹⁸F]NaF was developed through a straightforward modification of the commercial dispenser Clio (Comecer S.p.A., Italy) and without the need of a synthesis module. The full production, processing and dispensing of [¹⁸F]NaF were entirely carried out on the same batch using only the dispensing module. Process validation was carried according to GMP guidelines to ensure consistency of [¹⁸F]NaF quality with international standards. The final radiopharmaceutical met all quality criteria specified by Ph. Eur. and chemical, radionuclidic and radiochemical impurities were significantly below the required limits.</p><h3>Conclusion</h3><p>A new simple and reliable procedure developed for the preparation and dispensing of injectable [¹⁸F]NaF in less than 10 min with a radiochemical yield &gt; 97% (decay corrected) has been successfully developed. Notably, the proposed method also allows the preparation of [¹⁸F]NaF using the residual fluorine-18 activity remaining after a [¹⁸F]FDG production run, thus making it immediately accessible to patients for further PET imaging investigations.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00329-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143107978","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 evaluation of spirobenzovesamicols as potential 11C-PET tracer alternatives to [18F]FEOBV for vesicular acetylcholine transporter (VAChT) imaging","authors":"Hugo Helbert,&nbsp;Winnie Deuther-Conrad,&nbsp;Michel de Haan,&nbsp;Barbara Wenzel,&nbsp;Gert Luurtsema,&nbsp;Wiktor Szymanski,&nbsp;Peter Brust,&nbsp;Rudi A. J. O. Dierckx,&nbsp;Ben L. Feringa,&nbsp;Philip H. Elsinga","doi":"10.1186/s41181-025-00327-w","DOIUrl":"10.1186/s41181-025-00327-w","url":null,"abstract":"<div><h3>Background</h3><p>Through its central role in neurotransmission, the vesicular acetylcholine transporter (VAChT) is an increasingly valuable target for positron emission tomography (PET). VAChT ligands have been mostly derived from the vesamicol structure, but with limitations in available labelling methods and selectivity for VAChT against σ receptors being a common pitfall of such compounds, the development of selective VAChT tracers remains a challenge. Modern labelling techniques, in this case the [¹¹C]MeLi cross-coupling methodology, expands labelling opportunities, allowing to explore novel vesamicol-based structures as potential PET-tracers.</p><h3>Results</h3><p>A series of vesamicol derivatives was synthesized and their binding towards VAChT, σ1 and σ2 receptors assessed. Of all compound tested, (-)-2-methylspirobenzovesamicol ((-)-<b>4</b>) was the most promising with a 16 ± 4 nM affinity towards VAChT, a 29-fold weaker affinity for σ1 receptors and negligible binding (&gt; 1 μM) towards σ2 receptors. The radiolabelling was performed from the corresponding bromide using a [¹¹C]MeLi cross-coupling protocol, yielding 2-[¹¹C]methylspirobenzovesamicol in 32–37% RCY. New in vitro binding data is also made available for (-)-FEOBV with human-sourced σ1 receptors, revealing a 300-fold stronger affinity for VAChT compared to σ receptors.</p><h3>Conclusion</h3><p>(-)-2-methylspirobenzovesamicol was identified as a potent and selective VAChT ligand, with moderate to low affinity for σ receptors, and its racemate was radiolabeled in good radiochemical yields with Carbon-11. At this stage, [¹¹C]-<i>methyl</i>-2-methylspirobenzovesamicol appears a promising ¹¹C-PET tracer for VAChT imaging.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-025-00327-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078307","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 N-acetyltransferase 10 inhibitor [11C]remodelin: synthesis and preliminary positron emission tomography study in mice","authors":"Rui Luo,&nbsp;Yiding Zhang,&nbsp;Katsushi Kumata,&nbsp;Lin Xie,&nbsp;Yusuke Kurihara,&nbsp;Masanao Ogawa,&nbsp;Tomomi Kokufuta,&nbsp;Nobuki Nengaki,&nbsp;Feng Wang,&nbsp;Ming-Rong R. Zhang","doi":"10.1186/s41181-025-00330-1","DOIUrl":"10.1186/s41181-025-00330-1","url":null,"abstract":"<div><h3>Background</h3><p>4-(4-Cyanophenyl)-2-(2-cyclopentylidenehydrazinyl)thiazole (remodelin) is a potent <i>N</i>-acetyltransferase 10 (NAT10) inhibitor. This compound inhibits tumors and weakens tumor resistance to antitumor drugs. Moreover, remodelin has been found to enhance healthspan in an animal model of the human accelerated ageing syndrome. In this study, we synthesized C-11-labelled remodelin ([¹¹C]remodelin) for the first time as a positron emission tomography (PET) probe and assessed its biodistribution in mice using PET.</p><h3>Results</h3><p>[¹¹C]Remodelin was synthesized by the reaction of a boron ester precursor (<b>1</b>) with hydrogen [¹¹C]cyanide, which was prepared from the cyclotron-produced [¹¹C]carbon dioxide via [¹¹C]methane. The decay-corrected radiochemical yield of [¹¹C]remodelin was 6.2 ± 2.3% (<i>n</i> = 20, based on [¹¹C]carbon dioxide) with a synthesis time of 45 min and radiochemical purity of &gt; 90%. A PET study with [¹¹C]remodelin showed high uptake of radioactivity in the heart, liver, and small intestine of mice. The metabolite analysis indicated moderate metabolism of [¹¹C]remodelin in the heart.</p><h3>Conclusions</h3><p>In the present study, we successfully synthesized [¹¹C]remodelin and assessed its biodistribution of radioactivity in the mouse organs and tissues with PET. We are planning to prepare tumor and inflammatory models in which overexpression of NAT10 is possibly induced and conduct PET imaging for these animal models with [¹¹C]remodelin to elucidate the relationship between NAT10 and diseases.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062676","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}