EJNMMI Radiopharmacy and Chemistry最新文献

{"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}

{"title":"Lutetium-177 labeled iPD-L1 as a novel immunomodulator for cancer-targeted radiotherapy","authors":"Myrna Luna-Gutiérrez,&nbsp;Erika Azorín-Vega,&nbsp;Rigoberto Oros-Pantoja,&nbsp;Blanca Ocampo-García,&nbsp;Pedro Cruz-Nova,&nbsp;Nallely Jiménez-Mancilla,&nbsp;Gerardo Bravo-Villegas,&nbsp;Clara Santos-Cuevas,&nbsp;Laura Meléndez-Alafort,&nbsp;Guillermina Ferro-Flores","doi":"10.1186/s41181-025-00328-9","DOIUrl":"10.1186/s41181-025-00328-9","url":null,"abstract":"<div><h3>Background</h3><p>Cancer immunotherapy is a relatively new approach to cancer treatment. Peptides that target specific pathways and cells involved in immunomodulation can potentially improve the efficacy of cancer therapy. Recently, we reported iPD-L1 as a novel inhibitor peptide that specifically targets the cancer cell ligand PD-L1 (programmed death ligand 1). PD-L1 is responsible for inhibiting the immune checkpoint protein PD-1 expressed by regulatory T cells. On the other hand, anti-PD-L1 immunotherapy in combination with external beam radiotherapy has shown improved outcomes in the treatment of breast and lung cancer. The aim of this research was to prepare ¹⁷⁷Lu-labeled iPD-L1 and to preclinically evaluate its radiotherapeutic potential and role as a tumor immunomodulator by measuring macrophage activation, IL-10, TGFβ, and PD-L1 expression in 4T1 triple-negative breast cancer cells and murine 4T1 tumors after treatment with ¹⁷⁷Lu-iPD-L1.</p><h3>Results</h3><p>The iPD-L1 ligand, characterized by UPLC mass, UV-Vis, and FT-IR spectroscopies, showed a chemical purity of 99%. The ¹⁷⁷Lu-iPD-L1 radiochemical purity was 98.9 ± 1.1%. In vitro and in vivo studies demonstrated radiotracer stability in human serum (&gt; 97% after 24 h evaluated by radio-HPLC), adequate affinity by the PDL1 protein (IC₅₀ = 4.21 nM), and specific detection for PD-L1 assessed in 4T1, HCT116, and AR42J cancer cells, in which PD-L1 expression was verified by immunofluorescence and Western Blot assays. After treatment with ¹⁷⁷Lu-iPD-L1 (0.4 Bq/cell), flow cytometry results showed a significant decrease in cell viability of 4T1 cells (dead 56.2%) compared to ¹⁷⁷LuCl₃ (dead 34.2%) and untreated cells (dead 9.4%). With high tumor uptake (6.97 ± 1.04%ID) and hepatobiliary and renal clearance, lutetium-177-labeled iPD-L1 delivered a tumor dose of 27 Gy/37 MBq and less than 0.36 Gy/37 MBq to non-source organs. PD-L1 positive tumors showed a significant increase in activated macrophages, PD-L1, IL-10, and TGFβ expression levels after ¹⁷⁷Lu-iPD-L1 treatment as evaluated by ELISA assay and immunohistochemistry.</p><h3>Conclusions</h3><p>Therefore, this study warrants further dosimetric and clinical studies to determine the immunomodulatory effect and therapeutic efficacy of ¹⁷⁷Lu-iPD-L1 in treating PD-L1-positive tumors in combination with anti-PD-1/PD-L1 immunotherapy protocols.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021380","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":"Rapid fabrication and dissolution of pressed 58Ni/Mg matrix targets for 55Co production","authors":"Jonathan Siikanen,&nbsp;Stefan Milton,&nbsp;Klas Bratteby,&nbsp;Wilson Lin,&nbsp;Jonathan W. Engle,&nbsp;Emma Jussing,&nbsp;Thuy A. Tran","doi":"10.1186/s41181-024-00324-5","DOIUrl":"10.1186/s41181-024-00324-5","url":null,"abstract":"<div><h3>Background</h3><p>Beyond the use of conventional short-lived PET radionuclides, there is a growing interest in tracking larger biomolecules and exploring radiotheranostic applications. One promising option for imaging medium-sized molecules and peptides is ⁵⁵Co (T₁/₂ = 17.5 h, β⁺ = 76%), which enables imaging of new and already established tracers with blood circulation of several hours. Additionally, ⁵⁵Co can be paired with the Auger-Meitner emitter ^58mCo (T₁/₂ = 9 h, 100% IC) for radiotheranostic applications. Here we report on ⁵⁵Co production via the ⁵⁸Ni(p,α)⁵⁵Co reaction channel using pressed ⁵⁸Ni and Mg matrix targets.</p><h3>Results</h3><p>This set up is capable to produce and isolate 240 ± 20 MBq [⁵⁵Co]Co^+ 2 (80% RCY) with 4 ml 0.25 M HEPES at 35 min post End Of Bombardment for 3 h, 25 µA protons irradiation. The RNP of the eluate is 99.98 ± 0.014% as measured 2 h &amp; 17 h post EOB. AMA was determined to 1.5 ± 0.5 GBq/µmol [⁵⁵Co]Co-DOTA at EOB. Mg dissolves rapidly in the acid mixture, leaving behind a porous, sponge-like Ni matrix increasing the surface area of the Ni and therefore accelerating the dissolution.</p><h3>Conclusion</h3><p>We present a novel, simple, and rapid method to produce ⁵⁵Co with pressed ⁵⁸Ni/Mg matrix targets enabling faster target fabrication and dissolution. By using a simple hydraulic press, mechanically stable target coins useful for solid target irradiation are fabricated within 5 min and can be dissolved in 10 min at room temperature. The foils remain intact after irradiation and can endure irradiation conditions providing sufficient activity (&gt; 200 MBq) for clinical doses. The method presented here using Mg as a support metal for fixation of the actual target material into target coins is applicable for other target combinations as well. Using Mg as a support metal is suitable due to its thermal conductivity, low activation, minimal impact on purification chemistry, softness, ductility, and rapid dissolution in acid.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00324-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995753","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":"Evaluation of maSSS/maSES-PEG2-RM26 for their potential therapeutic use after labeling with Re-188. Could their [99mTc]Tc-labeled counterparts be used to estimate dosimetry?","authors":"Panagiotis Kanellopoulos,&nbsp;Quanyi Yu,&nbsp;Abouzayed Abouzayed,&nbsp;Ekaterina Bezverkhniaia,&nbsp;Vladimir Tolmachev,&nbsp;Anna Orlova","doi":"10.1186/s41181-024-00326-3","DOIUrl":"10.1186/s41181-024-00326-3","url":null,"abstract":"<div><h3>Background</h3><p>Gastrin releasing peptide receptor (GRPR)-directed radiopharmaceuticals for targeted radionuclide therapy may be a very promising addition in prostate and breast cancer patient management. Aiming to provide a GRPR-targeting theranostic pair, we have utilized the Tc-99m/Re-188 radiometal pair, in combination with two bombesin based antagonists, maSSS-PEG2-RM26 and maSES-PEG2-RM26. The two main aims of the current study were (i) to elucidate the influence of the radiometal-exchange on the biodistribution profile of the two peptides and (ii) to evaluate the feasibility of using the [^99mTc]Tc labeled counterparts for the dosimetry estimation for the [¹⁸⁸Re]Re-labeled conjugates.</p><h3>Results</h3><p>Both peptides were successfully labeled with Re-188 and evaluated both in vitro and in vivo. In GRPR expressing PC-3 cells, both [¹⁸⁸Re]Re-labeled peptides displayed high cellular uptake (8.5 ± 0.1% and 5 ± 0.3% of added activity, respectively), heavily GRPR-driven, while retaining the radioantagonistic profile with slow internalization rates. Both agents demonstrated high receptor affinity when loaded with ^natRe (7.5 nM and 8 nM, respectively). When tested in vivo in GRPR expressing PC-3 xenografts, both radioantagonists demonstrated high tumor accumulation (6.3 ± 0.5%IA/g and 5 ± 1%IA/g at 1 h pi, respectively), with good retention over time (4 ± 2%IA/g and 3.1 ± 0.1%IA/g at 4 h pi, respectively). In addition, their biodistribution profiles were closely mimicking their [^99mTc]Tc-labeled counterparts. Statistically significant lower tumor uptake was found for both conjugates labeled with Tc-99m, which may result in underestimation of the dose delivered to the tumor.</p><h3>Conclusions</h3><p>All the results indicate that Tc-99 m could be used for dosimetry evaluation for the two [¹⁸⁸Re]Re-labeled radioligands, with minimal alterations in their biodistribution pattern and tumor targeting capabilities.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00326-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compact and cGMP-compliant automated synthesis of [18F]FSPG on the Trasis AllinOne™","authors":"Rizwan Farooq,&nbsp;Thibault Gendron,&nbsp;Richard S. Edwards,&nbsp;Timothy H. Witney","doi":"10.1186/s41181-024-00322-7","DOIUrl":"10.1186/s41181-024-00322-7","url":null,"abstract":"<div><h3>Background</h3><p>(<i>S</i>)-4-(3-¹⁸F-Fluoropropyl)-ʟ-glutamic acid ([¹⁸F]FSPG) is a positron emission tomography radiotracer used to image system x_c⁻, an antiporter that is upregulated in several cancers. Not only does imaging system x_c⁻ with [¹⁸F]FSPG identify tumours, but it can also provide an early readout of response and resistance to therapy. Unfortunately, the clinical production of [¹⁸F]FSPG has been hampered by a lack of robust, cGMP-compliant methods. Here, we report the automated synthesis of [¹⁸F]FSPG on the Trasis AllinOne™, overcoming previous limitations to provide a user-friendly method ready for clinical adoption.</p><h3>Results</h3><p>The optimised method provided [¹⁸F]FSPG in 33.5 ± 4.9% radiochemical yield in just 35 min when starting with 18–25 GBq. Importantly, this method could be scaled up to &gt; 100 GBq starting activity with only a modest reduction in radiochemical yield, providing [¹⁸F]FSPG with a molar activity of 372 ± 65 GBq/µmol and excellent radiochemical purity (96.8 ± 1.1%). The formulated product was stable when produced with these high starting activities.</p><h3>Conclusions</h3><p>We have developed the first automated synthesis of [¹⁸F]FSPG on the Trasis AllinOne™. The method produces [¹⁸F]FSPG with excellent radiochemical purity and in high amounts suitable for large clinical trials and off-site distribution. The method expands the number of synthesis modules capable of producing [¹⁸F]FSPG and has been carefully designed for cGMP compliance to simplify regulatory approval for clinical production. The methods developed for the purification of high-activity [¹⁸F]FSPG are transferrable and should aid the development of clinical [¹⁸F]FSPG productions on other synthesis modules.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00322-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994839","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":"Preclinical evaluation of the potential PARP-imaging probe [carbonyl-11C]DPQ","authors":"Katarína Benčurová,&nbsp;Theresa Balber,&nbsp;Victoria Weissenböck,&nbsp;Lukas Kogler,&nbsp;Joachim Friske,&nbsp;Verena Pichler,&nbsp;Markus Mitterhauser,&nbsp;Marcus Hacker,&nbsp;Cécile Philippe,&nbsp;Marius Ozenil","doi":"10.1186/s41181-024-00323-6","DOIUrl":"10.1186/s41181-024-00323-6","url":null,"abstract":"<div><h3>Background</h3><p>Poly (ADP-ribose) polymerase (PARP) enzymes are crucial for the repair of DNA single-strand breaks and have become key therapeutic targets in homologous recombination-deficient cancers, including prostate cancer. To enable non-invasive monitoring of PARP-1 expression, several PARP-1-targeting positron emission tomography (PET) tracers have been developed. Here, we aimed to preclinically investigate [<i>carbonyl</i>-¹¹C]DPQ as an alternative PARP-1 PET tracer as it features a strongly distinct chemotype compared to the frontrunners [¹⁸F]FluorThanatrace and [¹⁸F]PARPi.</p><h3>Results</h3><p>[<i>carbonyl</i>-¹¹C]DPQ was synthesised in a GE TracerLab FXC2 module, yielding sufficient activity (940 ± 410 MBq), molar activity (53 ± 16 GBq/µmol) and radiochemical purity (&gt; 97%) for subsequent preclinical evaluation. [<i>carbonyl</i>-¹¹C]DPQ showed high stability in formulation, in human plasma, and when incubated with human liver microsomes. In vitro, similar specific uptake was observed in both PC3 prostate cancer cells and CHO-K1 Chinese hamster ovary cells. However, in vivo studies using fertilised chicken eggs (in ovo model) revealed poor and non-displaceable tumour accumulation in PC3-derived xenografts, despite confirmed vascularisation and PARP-1 expression. Rapid uptake was observed in the liver (10 min), with less than 30% of the intact compound remaining in the liver 70 min post-injection.</p><h3>Conclusions</h3><p>Although [<i>carbonyl</i>-¹¹C]DPQ demonstrated metabolic stability and specific binding in vitro, suboptimal tumour-targeting properties and pronounced liver metabolism were observed in ovo. Therefore, further animal experiments with mammalian models were not indicated.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00323-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940684","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}