{"title":"Energy dependent production and radionuclidic purity of (:{:}^{47}mathbf{S}mathbf{c}:)from (:{:}^{48}mathbf{C}mathbf{a}(varvec{p},varvec{x}varvec{n}):)reactions: a combined theoretical and data from EXFOR library using the EMPIRE code","authors":"Hailu Geremew Zeleke","doi":"10.1186/s41181-026-00463-x","DOIUrl":"10.1186/s41181-026-00463-x","url":null,"abstract":"<div><h3>Background</h3><p>The production of Scandium-47, a promising radionuclide for targeted radionuclide therapy, was investigated via proton-induced reactions on enriched Ca-48 using the EMPIRE nuclear reaction code. A comparative analysis between EMPIRE simulations and experimental data extracted from EXFOR was performed for Sc-48, Sc-47, and Sc-46 production channels, showing good overall agreement, as indicated by low MAPE values and correlation coefficients close to unity. Excitation functions for the ⁴⁸Ca(p, n)⁴⁸Sc, ⁴⁸Ca(p,2n)⁴⁷Sc, and ⁴⁸Ca(p,3n)⁴⁶Sc reactions were calculated over a wide proton energy range, and thick-target yields were evaluated using stopping power data. The RNP of ⁴⁷Sc was determined as a function of incident proton energy.</p><h3>Results</h3><p>The results show that radionuclide production strongly depends on proton energy. At low energies (0–12 MeV), the ⁴⁸Ca(p, n) reaction dominates, leading to significant ⁴⁸Sc formation and low RNP (~ 9%). In the intermediate energy range (12–28 MeV), the yield of ⁴⁷Sc increases substantially while maintaining relatively high purity. A more detailed analysis identifies the 16.5–21.5 MeV window as optimal, providing high yield with an RNP of approximately 94%. At higher energies (28–50 MeV), the increasing contribution of the ⁴⁸Ca(p,3n) reaction results in significant formation of long-lived ⁴⁶Sc, reducing radionuclidic purity.</p><h3>Conclusion</h3><p>These findings demonstrate that careful selection of the proton energy window is essential for optimizing both production yield and RNP, providing practical guidance for cyclotron-based production of ⁴⁷Sc for medical applications.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00463-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337376","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}
Aivija Grundmane, Caterina F. Ramogida, Valery Radchenko
{"title":"Recycling-compatible electroplating of enriched tin-119 targets for the production of antimony-119 for targeted Auger electron therapy","authors":"Aivija Grundmane, Caterina F. Ramogida, Valery Radchenko","doi":"10.1186/s41181-026-00468-6","DOIUrl":"10.1186/s41181-026-00468-6","url":null,"abstract":"<div><h3>Background</h3><p>Antimony-119 (<sup>119</sup>Sb) is a radionuclide of interest for targeted Auger electron therapy. Isotopically pure <sup>119</sup>Sb can be produced by proton irradiation of enriched tin-119 (<sup>119</sup>Sn) targets in conventional widely available low energy medical cyclotrons. Enriched <sup>119</sup>Sn is very costly (~ 20,000 CAD/gram), requiring recycling of the target material to make this production route economically viable. Herein, we investigate three Sn electroplating methods, evaluate the target quality, as well as method compatibility with subsequent <sup>119</sup>Sb radiochemical purification steps.</p><h3>Results</h3><p>Three electroplating bath compositions (Sn(II) sulfate, Sn(IV) sols, and Sn(IV) chloride) for Sn deposition were tested and successfully implemented. One of the methods, utilizing a Sn(IV) chloride bath solution was able to achieve quantitative electroplating efficiency (98 ± 3% Sn deposited after 72 h), and an overall post-purification recovery of 84 ± 6% Sn, accounting for losses during the dissolution and purification steps. Moreover, this electroplating bath composition yielded the most homogeneous targets, both with respect to its structure, as well as lack of contaminants and the highest weight percentage of surface Sn (88 ± 2 wt%).</p><h3>Conclusions</h3><p>All three electroplating baths investigated were able to yield Sn targets of sufficient quality for irradiation, although they showed markedly different surface morphology and surface elemental composition. Sn(IV) chloride bath solution was found to be capable of recycling of <sup>119</sup>Sn as recovered from the <sup>119</sup>Sb purification step. Furthermore, this method yielded the best results in all aspects, displaying the highest homogeneity in surface morphology and elemental composition, which are desirable characteristics for beam tolerance and radionuclidic purity.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00468-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337363","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}
Joseph A. Ioppolo, Leila R. Hill, Alexander W. E. Sadler, Amit Hetsron, Laurence Morandeau, John Doan, Kenneth K. C. Hong, Andrew T. King, Tzong-Tyng Hung, Carl Power, Louis M. Rendina
{"title":"Easy and versatile preparation of 68Ga- and Al18F-labelled arylphosphonium salts from a common precursor: stability and preliminary in vivo PET/CT evaluation","authors":"Joseph A. Ioppolo, Leila R. Hill, Alexander W. E. Sadler, Amit Hetsron, Laurence Morandeau, John Doan, Kenneth K. C. Hong, Andrew T. King, Tzong-Tyng Hung, Carl Power, Louis M. Rendina","doi":"10.1186/s41181-026-00466-8","DOIUrl":"10.1186/s41181-026-00466-8","url":null,"abstract":"<div><h3>Background</h3><p>The primary aim of this work was to develop and optimise a facile synthesis of radiolabelled arylphosphonium compounds [<sup>68</sup>Ga]<b>2</b> and [<sup>18</sup>F]<b>3</b> from the common macrocyclic precursor 1-(4-(((triphenylphosphonium)yl)methyl)benzyl)-4,7-bis(carboxymethyl)-1,4,7-triazacyclononane acetate (<b>1</b>). A series of reaction conditions, including temperature, time, ethanol content and reagent concentration were tested to arrive at optimised conditions for labelling with either <sup>68</sup>Ga or Al<sup>18</sup>F. Preclinical evaluations including stability in formulation and in serum, and preliminary imaging in healthy wild type C57BL/6 mice were completed.</p><h3>Results</h3><p>The target compounds [<sup>68</sup>Ga]<b>2</b> and [<sup>18</sup>F]<b>3</b> could be prepared in near quantitative yields using the optimised conditions. Although the stability of both tracers was acceptable in formulation containing 10% ethanol and 0.5 mg/mL sodium ascorbate, and the stability of [<sup>18</sup>F]<b>3</b> in serum was ideal, the stability of [<sup>68</sup>Ga]<b>2</b> in serum was sub-optimal. Dynamic PET/CT imaging in mice over 60 min revealed no uptake in bone, rapid renal excretion and more prolonged uptake in the liver and intestine for [<sup>18</sup>F]<b>3</b> compared to [<sup>68</sup>Ga]<b>2</b>.</p><h3>Conclusion</h3><p>The simple synthesis of [<sup>68</sup>Ga]<b>2</b> and [<sup>18</sup>F]<b>3</b> from a common precursor was achieved and was easily translatable. Although the utility of [<sup>68</sup>Ga]<b>2</b> and [<sup>18</sup>F]<b>3</b> for myocardium or cancer imaging is limited, this successful labelling strategy may be applied to a library of other compounds for use in imaging other targets in the body.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00466-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337327","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}
David Kryza, Pierre Le Fur, Jean Noël Badel, Clément Morgat, Fouzi Khayi, Anne-Laure Giraudet
{"title":"Fully GMP-complient radiosynthesis of [161Tb]Tb-PSMA-1 using the miniAiO synthesizer for clinical translation","authors":"David Kryza, Pierre Le Fur, Jean Noël Badel, Clément Morgat, Fouzi Khayi, Anne-Laure Giraudet","doi":"10.1186/s41181-026-00467-7","DOIUrl":"10.1186/s41181-026-00467-7","url":null,"abstract":"<div><h3>Background</h3><p>Terbium‑161 (<sup>161</sup>Tb) is an emerging radionuclide for targeted radionuclide therapy that combines β⁻ emissions with short‑range conversion and Auger electrons, increasing its efficacy against micrometastatic and low‑volume prostate cancer. This study aimed to develop, optimize, and validate a fully automated good manufacturing practice (GMP)-compliant radiosynthesis of [<sup>161</sup>Tb]Tb-PSMA‑1 for clinical application. Radiolabeling parameters were systematically investigated via different buffer systems (acetate, ammonium acetate, and ascorbate), labeling temperatures (24–95 °C), and ethanol supplementation. Process validation was performed on three independent batches produced under routine conditions (7.4–11.5 GBq) via a Trasis MiniAiO synthesizer. Comprehensive quality control included radionuclidic identification, radiochemical purity (RCP), pH, sterility, endotoxin testing, and container–content interaction assessment.</p><h3>Results</h3><p>Efficient radiolabeling was achieved under all the tested conditions, with RCPs consistently exceeding 97%. Optimal performance was observed when ascorbate buffer was used at 95 °C, yielding approximately 99% RCP at the end of synthesis. The addition of 40% (V/V) ethanol improved both the labeling efficiency and radiochemical stability, enabling high RCP even at lower temperatures. The final formulation demonstrated excellent stability, maintaining RCP ≥ 97.5% up to 48 h post-synthesis. All validation batches met predefined release criteria in accordance with Ph. Eur. Monograph radiopharmaceutical preparations. The total synthesis time was less than 30 min.</p><h3>Conclusion</h3><p>A robust, rapid, and fully automated GMP-compliant method for [<sup>161</sup>Tb]Tb-PSMA‑1 production was successfully established. The high radiochemical purity, stability, and reproducibility support its suitability for routine clinical use and decentralized distribution. This work represents a key step toward the clinical translation of [<sup>161</sup>Tb]Tb-labeled PSMA radioligands for improved management of advanced prostate cancer.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00467-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300579","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}
Marion Berdal, Surasa Nagachinta, Ximena Langsberg, Vaiva Gaspariunaite, Sam Massa, Ana Rita Pombo Antunes, Dimitrios Mantzilas, Matthias D’Huyvetter, Laurent Navarro
{"title":"Automated and manual synthesis of [68Ga]Ga-DOTA-4AH29 intended for PET-imaging of FAP-expression","authors":"Marion Berdal, Surasa Nagachinta, Ximena Langsberg, Vaiva Gaspariunaite, Sam Massa, Ana Rita Pombo Antunes, Dimitrios Mantzilas, Matthias D’Huyvetter, Laurent Navarro","doi":"10.1186/s41181-026-00465-9","DOIUrl":"10.1186/s41181-026-00465-9","url":null,"abstract":"<div><h3>Background</h3><p>Fibroblast activation protein is a well-established target for tumour imaging, and single-domain antibodies (sdAb) offer favourable pharmacokinetic properties for PET applications. However, the translation of sdAb-based radiotracers into robust and clinically applicable manufacturing processes remains limited. Previously, preclinical protocol for the production of [<sup>68</sup>Ga]Ga-DOTA-4AH29 has been reported. In this study, this process was adapted for clinical use. Both a manual, kit-based approach and automated synthesis on two different platforms were developed. Process robustness was assessed through a stress study evaluating key parameters, and compatibility with two <sup>68</sup>Ga generator systems was investigated.</p><h3>Results</h3><p>Efficient radiolabelling was achieved at 50 °C for 10 min, with radiochemical conversion exceeding 90% and no need for purification. Both automated and manual processes showed consistent performance, with radiochemical purities of 99.5 ± 0.5% (<i>n</i> = 9) and 96.3 ± 1.5% (<i>n</i> = 8) as determined by iTLC and SE-HPLC respectively, with associated non-decay-corrected radiochemical yields of 78.3 ± 3.3% (<i>n</i> = 9) and 76.9 ± 2.1% (<i>n</i> = 8). The main source of activity loss was the radioactive decay of <sup>68</sup>Ga.The process remained stable across a range of activities and buffer conditions. Comparable results were obtained with both <sup>68</sup>Ga generator systems, with no observable impact on product quality. The final product was stable for at least 3 h at RT, with preserved binding capacity.</p><h3>Conclusion</h3><p>A robust and reproducible manufacturing process for [<sup>68</sup>Ga]Ga-DOTA-4AH29 was established, supporting both automated and manual clinical production. This approach will facilitate broader access to sdAb-based PET imaging across clinical centres.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275537","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 a fluorine-18-labeled indocyanine green analog for PET imaging of hepatic function","authors":"Khashayar Vakili, Alan Packard","doi":"10.1186/s41181-026-00464-w","DOIUrl":"10.1186/s41181-026-00464-w","url":null,"abstract":"<div><h3>Background</h3><p>Accurate assessment of liver function and biliary excretion is a key aspect in the medical and surgical management of various liver conditions. Dynamic nuclear imaging techniques such as PET (positron emission tomography) offer the potential to directly quantify hepatic clearance and hepatobiliary function. Indocyanine green (ICG) is a fluorescent dye that is used to indirectly evaluate liver function via its plasma clearance, but its optical properties preclude deep tissue imaging. Here, we report the synthesis and preclinical evaluation of a novel fluorine-18 labeled ICG derivative ([<sup>18</sup>F]SFB-ICG; SFB = <i>N</i>-succinimidyl-4-[<sup>18</sup>F]fluorobenzoate) as a potential PET radiotracer for noninvasive assessment of hepatobiliary function.</p><h3>Results</h3><p>ICG was successfully labeled with <sup>18</sup>F: The product was obtained in high chemical and radionuclidic purity, albeit in relatively low yield (0.25–1.0%, non-decay-corrected). PET imaging demonstrated rapid hepatic uptake with a peak standardized uptake value (SUV) of 8.6 ± 0.8 at 20 min post-injection. The tracer exhibited prompt biliary excretion as demonstrated by a gallbladder SUV of 22.3 ± 1.4 at 45 min post-injection. Time–activity curves confirmed hepatic clearance similar to unlabeled ICG. At 4 h PI, the SUVs of selected organs were: liver 4.7 ± 0.5; lungs 0.15 ± 0.02; small intestine 3.68 ± 0.76; spleen 2.25 ± 0.88; large intestine 4.9 ± 1.7. Renal uptake and clearance was minimal. The whole blood SUV at 1 and 4 h post-injection was 0.47 ± 0.04 and 0.20 ± 0.02, respectively. No overt adverse effects were observed during the 4-h study period.</p><h3>Conclusions</h3><p>This study presents [<sup>18</sup>F]SFB-ICG as a novel PET tracer for real-time, quantitative assessment of liver function and biliary clearance in vivo. The tracer exhibits favorable pharmacokinetics, high liver specificity, and excellent correlation with established hepatobiliary physiology. Thus, <sup>18</sup>F-SFB-ICG represents a lead compound that warrants further development—including yield optimization, stability and toxicity characterization, and evaluation in animal models of liver disease—for potential applications in hepatic functional imaging, surgical planning, characterization of liver masses, and assessment of biliary pathology.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256815","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}
Arthur C. K. Chu, Felix Ho, Conrad Chan, Zhongli Cai, Yumeela Ganga-Sah, Parmissa Randhawa, Caterina F. Ramogida, Valery Radchenko, Raymond M. Reilly
{"title":"Panitumumab labeled with Auger electron-emitting 197gHg/197mHg: cytotoxicity on human breast cancer cells and tumour and normal tissue uptake in mice with EGFR-overexpressing breast cancer xenografts","authors":"Arthur C. K. Chu, Felix Ho, Conrad Chan, Zhongli Cai, Yumeela Ganga-Sah, Parmissa Randhawa, Caterina F. Ramogida, Valery Radchenko, Raymond M. Reilly","doi":"10.1186/s41181-026-00449-9","DOIUrl":"10.1186/s41181-026-00449-9","url":null,"abstract":"<div><h3>Background</h3><p><sup>197g</sup>Hg and <sup>197m</sup>Hg are attractive radionuclides for radioimmunotherapy of cancer due to their abundant Auger electron emissions (23.2 and 19.4 electrons/decay, respectively). Our aim was to study the cytotoxicity and DNA-damaging properties of panitumumab labeled with <sup>197g</sup>Hg/<sup>197m</sup>Hg on a panel of human breast cancer cells expressing different levels of epidermal growth factor receptor (EGFR) (10<sup>4</sup> to 10<sup>6</sup> EGFR/cell) and evaluate the tumour and normal tissue uptake of these radioimmunoconjugates in mice with EGFR-overexpressing MDA-MB-468 human breast cancer xenografts (10<sup>6</sup> EGFR/cell).</p><h3>Results</h3><p>Panitumumab was conjugated to 2-[4,7,10-tris(2-amino-2-oxoethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetamide (TCMC) or a sulphur-rich (NS<sub>4</sub>) bifunctional chelator to complex <sup>197g</sup>Hg/<sup>197m</sup>Hg or directly labeled with <sup>197g</sup>Hg/<sup>197m</sup>Hg through endogenous mercury binding sites. All radioimmunoconjugates bound specifically (87–91%) to EGFR on MDA-MB-468 cells. The radioimmunoconjugates were bound, internalized and imported into the nucleus of breast cancer cells dependent on their EGFR expression. Absorbed doses in the nucleus from the Auger electron emissions of <sup>197g</sup>Hg/<sup>197m</sup>Hg were correlated with EGFR expression level. The radioimmunoconjugates were most cytotoxic to MDA-MB-468 cells reducing their clonogenic survival to < 5% while unlabeled immunoconjugates did not decrease survival. Blocking EGFR with excess panitumumab restored clonogenic survival to ~ 60%. DNA double-strand breaks were highest in MDA-MB-468 cells and were decreased by blocking EGFR. Subcutaneous MDA-MB-468 tumours in athymic (nude) mice were imaged by SPECT/CT at 1 d and 3 d post-injection of the radioimmunoconjugates. Tumour uptake on images and in biodistribution studies was decreased by co-administering an excess of panitumumab. High kidney uptake was observed.</p><h3>Conclusions</h3><p>Panitumumab was complexed to <sup>197g</sup>Hg/<sup>197m</sup>Hg after conjugation to a bifunctional chelator or labeled directly with <sup>197g</sup>Hg/<sup>197m</sup>Hg. These radioimmunoconjugates bound specifically to EGFR on human breast cancer cells and caused DNA double-strand breaks that decreased their clonogenic survival. The radioimmunoconjugates localized in EGFR-overexpressing MDA-MB-468 tumours in mice but there was high kidney uptake, suggesting in vivo release of some <sup>197g</sup>Hg/<sup>197m</sup>Hg. Competition between complexation of <sup>197g</sup>Hg/<sup>197m</sup>Hg to a bifunctional chelator and binding to endogenous mercury binding sites in panitumumab presents challenges for radiolabeling and may explain the apparent release of some <sup>197g</sup>Hg/<sup>197m</sup>Hg in vivo. Alternative labeling strategies such as a 2-step method involving conjugation of the preformed <sup>197g</sup>Hg/<sup>197m","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00449-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248571","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}
Nino Jukić, Dražen Huić, Marijan Žuvić, Ivan Nemet, Sanda Rončević
{"title":"Development and evaluation of improved in-house procedure for radiolabelling of theranostic agent [177Lu]Lu-PSMA-617","authors":"Nino Jukić, Dražen Huić, Marijan Žuvić, Ivan Nemet, Sanda Rončević","doi":"10.1186/s41181-026-00462-y","DOIUrl":"10.1186/s41181-026-00462-y","url":null,"abstract":"<div><h3>Background</h3><p>Recent focus in the treatment of prostate cancer is directed towards the development and application of theranostic agents such as [<sup>177</sup>Lu]Lu-PSMA-617. It combines a PSMA-specific peptidomimetic with a therapeutical radionuclide <sup>177</sup>Lu and it is used in radioligand therapy that selectively delivers ionizing radiation into tumor cells. This study reports the automated radiosynthesis and quality control of an <i>in-house</i> [<sup>177</sup>Lu]Lu-PSMA-617 preparation and a direct comparison of its properties with the reference product (Pluvicto<sup>®</sup>).</p><h3>Results</h3><p>The radiopharmaceutical was obtained with > 95% radiochemical purity and > 96% radiochemical yield. The addition of ethanol improved radiochemical yield. The obtained product maintained > 98% radiochemical purity for up to 72 h in isotonic saline and human serum at 25 °C and 37 °C. The use of carrier-added <sup>177</sup>Lu for the <i>in-house</i> product and non-carrier-added <sup>177</sup>Lu for the reference product was confirmed by ICP-MS and gamma spectrometry methods.</p><h3>Conclusion</h3><p>Comparative quality control demonstrated generally equivalent quality attributes of <i>in-house</i> prepared product and the reference product, supporting <i>in-house</i> product suitability for routine clinical application at activities up to 7.4 GBq. This experiment showed that <i>in-house</i> production of <sup>177</sup>Lu-labeled theranostics is cost-effective method and can be automatized resulting in high quality and efficient production.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00462-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248580","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}
Olivier Perrin, Sarah Benkhoris, Johanne Vanney, Laurie Barthelemi, Vincent Boudousq, Emmanuel Deshayes, Claire Guisset, Ian Soulairol, Léa Rubira, Cyril Fersing, Daniele Alizé
{"title":"Expanding 68Ga radiolabeling capacity: off-label use of PSMA-11 single vial cold kits through aliquoting and dual generator utilization","authors":"Olivier Perrin, Sarah Benkhoris, Johanne Vanney, Laurie Barthelemi, Vincent Boudousq, Emmanuel Deshayes, Claire Guisset, Ian Soulairol, Léa Rubira, Cyril Fersing, Daniele Alizé","doi":"10.1186/s41181-026-00459-7","DOIUrl":"10.1186/s41181-026-00459-7","url":null,"abstract":"<div><h3>Background</h3><p>Prostate cancer is a highly prevalent malignancy, and PET imaging targeting prostate-specific membrane antigen (PSMA) has become essential for assessing recurrence, metastatic spread and eligibility for radioligand therapy, with a 38% increase in PSMA PET activity reported in France between 2022 and 2023. [<sup>68</sup>Ga]Ga-PSMA-11 prepared from single-vial cold kits such as Locametz<sup>®</sup> is now widely used, but kit cost, generator activity decay, and preparation procedures restricted to the marketing authorization dossier can limit the number of patients treated per day. This multicenter study investigated, under GMP conditions, an off-label strategy combining aliquoting of Locametz<sup>®</sup> vials with single or dual elutions from GalliaPharm<sup>®</sup> and GalliAd<sup>®</sup>Ge/<sup>68</sup>Ga generators and compared manual versus automated eluate fractionation. Four main approaches were evaluated: single or double elution for a full kit vial and single or double elution for two aliquots prepared 4–6 h apart, with full quality control according to the European Pharmacopoeia and the Locametz<sup>®</sup> summary of product characteristics (SmPC), as well as pharmaco-economic and dosimetric evaluations.</p><h3>Results</h3><p>Radiolabeling was effective under all conditions that remained within the kit’s buffer capacity. Single-generator labeling of complete vials or aliquots reliably yielded radiochemical purity (RCP) > 98% and stable complexes for 4 h. Aliquoting allowed for two separate preparations from a single Locametz<sup>®</sup> kit without compromising RCP. Elutions with dual generators proved efficient when the overall HCl 0.1 M volume was < 2.4 mL, resulting in activities reaching approximately 1.7 GBq with RCP ≥ 98%. High acidity or uneven distribution of aliquots caused pH variations and decreased RCP, causing a restricted number of failures (7%). Radiochemical yields achieved approximately 89% in refined standard procedures. Automated eluate fractionation greatly decreased radiation exposure to hands in comparison to manual handling. Pharmaco-economic evaluation showed significant cost savings per patient, with routine daily capacity ranging from 8 to 16 patients per kit, depending on generator age.</p><h3>Conclusions</h3><p>Aliquoting Locametz<sup>®</sup> vial and optimizing generator use significantly increase [<sup>68</sup>Ga]Ga-PSMA-11 production capacity. These strategies expand patient throughput and reduce costs of PSMA imaging. They provide a practical solution for centers facing rising PSMA PET demand and limited access to <sup>18</sup>F-PSMA tracers and can be potentially applied to other <sup>68</sup>Ga cold-kit radiopharmaceuticals.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00459-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148194259","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}
Ferris L. Bissen, Jose R. Blanco, Elizabeth M. Heidarisafa, Mojdeh Mahmoudian, Carolina A. Ferreira, Suzanne E. Lapi, Katharina A. Domnanich
{"title":"A comparative evaluation of chemical processes in anion exchange-based 62Zn/62Cu generator systems","authors":"Ferris L. Bissen, Jose R. Blanco, Elizabeth M. Heidarisafa, Mojdeh Mahmoudian, Carolina A. Ferreira, Suzanne E. Lapi, Katharina A. Domnanich","doi":"10.1186/s41181-026-00461-z","DOIUrl":"10.1186/s41181-026-00461-z","url":null,"abstract":"<div><h3>Background</h3><p>The interest in <sup>62</sup>Cu as a tracer for positron emission tomography (PET) has motivated several designs of a <sup>62</sup>Zn/<sup>62</sup>Cu radionuclide generator, the most common of which is based on anion exchange resin and a mixed HCl/NaCl eluent. Since commercial <sup>62</sup>Zn/<sup>62</sup>Cu generators are currently not available, the continued investigation of <sup>62</sup>Cu-based radiopharmaceuticals relies on the implementation of in-house generator systems. This work presents a systematic evaluation of several key parameters relevant to anion exchange-based <sup>62</sup>Zn/<sup>62</sup>Cu generators, including loading methodology, eluent composition, column dimensions, and <sup>62</sup>Cu activity quantification.</p><h3>Results</h3><p><sup>62</sup>Zn and the long-lived tracer <sup>65</sup>Zn were produced via proton irradiation of Cu targets and used to evaluate <sup>62</sup>Zn/<sup>62</sup>Cu generator performance. A simplified target processing method was developed for generator manufacturing, representing a practical approach for handling irradiated targets given the 9.2 h half-life of <sup>62</sup>Zn. Two generator loading approaches were compared, batch loading and fixed-bed loading. Fixed-bed loading yielded significantly lower zinc breakthrough than batch loading, with 1.1(2) × 10<sup>–3</sup>% compared to 20.6(1)% zinc eluted in the first 20 mL, while maintaining similar loading times. The commonly used 0.2 M HCl/1.8 M NaCl eluent was compared with 2 M HCl to assess the influence of eluent composition on <sup>62</sup>Cu elution efficiency and zinc breakthrough. The HCl eluent gave comparable <sup>62</sup>Cu elution efficiency, achieving an 84(4)% yield in a 1 mL elution, and lower zinc breakthrough. Resin mass was also evaluated, with 200 mg columns providing similar <sup>62</sup>Cu elution efficiencies to 150 mg columns while decreasing zinc breakthrough. Additionally, an improved methodology for <sup>62</sup>Cu activity quantification was developed to support reliable generator performance assessment. The produced <sup>62</sup>Cu was used to radiolabel diacetyl bis(N<sup>4</sup>-methylthiosemicarbazone) (ATSM) at high yield in both eluents and used in a proof-of-principal PET imaging study of a tumor-bearing mouse.</p><h3>Conclusions</h3><p>This study provides a comparison of loading method, eluent composition, and column configuration in anion exchange-based <sup>62</sup>Zn/<sup>62</sup>Cu generator systems. The results highlight how these parameters influence zinc breakthrough, <sup>62</sup>Cu elution efficiency, and downstream radiolabeling. This study outlines practical and transferable operating considerations that support the implementation of in-house <sup>62</sup>Zn/<sup>62</sup>Cu generator systems, contributing towards a broader availability of <sup>62</sup>Cu for future studies.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00461-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148215878","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}