Myrna Luna-Gutiérrez, Erika Azorín-Vega, Rigoberto Oros-Pantoja, Blanca Ocampo-García, Pedro Cruz-Nova, Nallely Jiménez-Mancilla, Gerardo Bravo-Villegas, Clara Santos-Cuevas, Laura Meléndez-Alafort, Guillermina Ferro-Flores
{"title":"Lutetium-177 labeled iPD-L1 as a novel immunomodulator for cancer-targeted radiotherapy","authors":"Myrna Luna-Gutiérrez, Erika Azorín-Vega, Rigoberto Oros-Pantoja, Blanca Ocampo-García, Pedro Cruz-Nova, Nallely Jiménez-Mancilla, Gerardo Bravo-Villegas, Clara Santos-Cuevas, Laura Meléndez-Alafort, 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 <sup>177</sup>Lu-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 <sup>177</sup>Lu-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 <sup>177</sup>Lu-iPD-L1 radiochemical purity was 98.9 ± 1.1%. In vitro and in vivo studies demonstrated radiotracer stability in human serum (> 97% after 24 h evaluated by radio-HPLC), adequate affinity by the PDL1 protein (IC<sub>50</sub> = 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 <sup>177</sup>Lu-iPD-L1 (0.4 Bq/cell), flow cytometry results showed a significant decrease in cell viability of 4T1 cells (dead 56.2%) compared to <sup>177</sup>LuCl<sub>3</sub> (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 <sup>177</sup>Lu-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 <sup>177</sup>Lu-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}
Jonathan Siikanen, Stefan Milton, Klas Bratteby, Wilson Lin, Jonathan W. Engle, Emma Jussing, Thuy A. Tran
{"title":"Rapid fabrication and dissolution of pressed 58Ni/Mg matrix targets for 55Co production","authors":"Jonathan Siikanen, Stefan Milton, Klas Bratteby, Wilson Lin, Jonathan W. Engle, Emma Jussing, 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 <sup>58m</sup>Co (T₁/₂ = 9 h, 100% IC) for radiotheranostic applications. Here we report on <sup>55</sup>Co production via the <sup>58</sup>Ni(p,α)<sup>55</sup>Co reaction channel using pressed <sup>58</sup>Ni and Mg matrix targets.</p><h3>Results</h3><p>This set up is capable to produce and isolate 240 ± 20 MBq [<sup>55</sup>Co]Co<sup>+ 2</sup> (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 & 17 h post EOB. AMA was determined to 1.5 ± 0.5 GBq/µmol [<sup>55</sup>Co]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 (> 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}
Panagiotis Kanellopoulos, Quanyi Yu, Abouzayed Abouzayed, Ekaterina Bezverkhniaia, Vladimir Tolmachev, Anna Orlova
{"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, Quanyi Yu, Abouzayed Abouzayed, Ekaterina Bezverkhniaia, Vladimir Tolmachev, 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 [<sup>99m</sup>Tc]Tc labeled counterparts for the dosimetry estimation for the [<sup>188</sup>Re]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 [<sup>188</sup>Re]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 <sup>nat</sup>Re (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 [<sup>99m</sup>Tc]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 [<sup>188</sup>Re]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}
Rizwan Farooq, Thibault Gendron, Richard S. Edwards, Timothy H. Witney
{"title":"Compact and cGMP-compliant automated synthesis of [18F]FSPG on the Trasis AllinOne™","authors":"Rizwan Farooq, Thibault Gendron, Richard S. Edwards, 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-<sup>18</sup>F-Fluoropropyl)-ʟ-glutamic acid ([<sup>18</sup>F]FSPG) is a positron emission tomography radiotracer used to image system x<sub>c</sub><sup>−</sup>, an antiporter that is upregulated in several cancers. Not only does imaging system x<sub>c</sub><sup>−</sup> with [<sup>18</sup>F]FSPG identify tumours, but it can also provide an early readout of response and resistance to therapy. Unfortunately, the clinical production of [<sup>18</sup>F]FSPG has been hampered by a lack of robust, cGMP-compliant methods. Here, we report the automated synthesis of [<sup>18</sup>F]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 [<sup>18</sup>F]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 > 100 GBq starting activity with only a modest reduction in radiochemical yield, providing [<sup>18</sup>F]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 [<sup>18</sup>F]FSPG on the Trasis AllinOne™. The method produces [<sup>18</sup>F]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 [<sup>18</sup>F]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 [<sup>18</sup>F]FSPG are transferrable and should aid the development of clinical [<sup>18</sup>F]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}
Katarína Benčurová, Theresa Balber, Victoria Weissenböck, Lukas Kogler, Joachim Friske, Verena Pichler, Markus Mitterhauser, Marcus Hacker, Cécile Philippe, Marius Ozenil
{"title":"Preclinical evaluation of the potential PARP-imaging probe [carbonyl-11C]DPQ","authors":"Katarína Benčurová, Theresa Balber, Victoria Weissenböck, Lukas Kogler, Joachim Friske, Verena Pichler, Markus Mitterhauser, Marcus Hacker, Cécile Philippe, 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>-<sup>11</sup>C]DPQ as an alternative PARP-1 PET tracer as it features a strongly distinct chemotype compared to the frontrunners [<sup>18</sup>F]FluorThanatrace and [<sup>18</sup>F]PARPi.</p><h3>Results</h3><p>[<i>carbonyl</i>-<sup>11</sup>C]DPQ was synthesised in a GE TracerLab FXC2 module, yielding sufficient activity (940 ± 410 MBq), molar activity (53 ± 16 GBq/µmol) and radiochemical purity (> 97%) for subsequent preclinical evaluation. [<i>carbonyl</i>-<sup>11</sup>C]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>-<sup>11</sup>C]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}
Emanuel Sporer, Claire Deville, Natan J. W. Straathof, Linda M. Bruun, Ulli Köster, Mikael Jensen, Thomas L. Andresen, Paul J. Kempen, Jonas R. Henriksen, Andreas I. Jensen
{"title":"Optimized chelator and nanoparticle strategies for high-activity 103Pd-loaded biodegradable brachytherapy seeds","authors":"Emanuel Sporer, Claire Deville, Natan J. W. Straathof, Linda M. Bruun, Ulli Köster, Mikael Jensen, Thomas L. Andresen, Paul J. Kempen, Jonas R. Henriksen, Andreas I. Jensen","doi":"10.1186/s41181-024-00309-4","DOIUrl":"10.1186/s41181-024-00309-4","url":null,"abstract":"<div><h3>Background</h3><p>Brachytherapy (BT) is routinely used in the treatment of various cancers. Current BT relies on the placement of large sources of radioactivity at the tumor site, requiring applicators that may cause local traumas and lesions. Further, they suffer from inflexibility in where they can be placed and some sources reside permanently in the body, causing potential long-term discomfort. These issues can be circumvented through injectable sources, prepared as biodegradable materials containing radionuclides that form solid seeds after administration. The level of radioactivity contained in such seeds must be sufficient to achieve substantial local irradiation. In this report, we investigate two different strategies for biodegradable BT seeds.</p><h3>Results</h3><p>The first strategy entails injectable seeds based on <sup>103</sup>Pd-labeled palladium-gold alloy nanoparticles ([<sup>103</sup>Pd]PdAuNPs). These were prepared by combining [<sup>103</sup>Pd]PdH<sub>2</sub>Cl<sub>4</sub> and AuHCl<sub>4</sub>, followed by lipophilic surface coating and dispersed in lactose octaisobutyrate and ethanol (LOIB:EtOH), in overall radiochemical yield (RCY) of 83%. With the second strategy, [<sup>103</sup>Pd]Pd-SSIB was prepared by conjugating the [16]aneS<sub>4</sub> chelator with lipophilic sucrose septaisobutyrate (SSIB) followed by complexation with [<sup>103</sup>Pd]PdH<sub>2</sub>Cl<sub>4</sub> (RCY = 99%) and mixed with LOIB:EtOH. [<sup>103</sup>Pd]Pd-SSIB was likewise formulated as injectable liquid forming seeds by mixing with LOIB. Both formulations reached activities of 1.0–1.5 GBq/mL and negligible release of radioactivity after injection of 100 µL (100–150 MBq) into aqueous buffer or mouse serum of less than 1% over one month.</p><h3>Conclusion</h3><p>Both strategies for forming injectable BT seeds containing high <sup>103</sup>Pd activity resulted in high radiolabeling yields, high activity per seed, and high activity retention. We consider both strategies suitable for BT, with the preferable strategy using a [16]aneS<sub>4</sub> chelator due to its higher biodegradability.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00309-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890056","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}
Daniel Gündel, Mudasir Maqbool, Rodrigo Teodoro, Friedrich-Alexander Ludwig, Anne Heerklotz, Magali Toussaint, Winnie Deuther-Conrad, Guy Bormans, Peter Brust, Klaus Kopka, Rareş-Petru Moldovan
{"title":"Development and evaluation of deuterated [18F]JHU94620 isotopologues for the non-invasive assessment of the cannabinoid type 2 receptor in brain","authors":"Daniel Gündel, Mudasir Maqbool, Rodrigo Teodoro, Friedrich-Alexander Ludwig, Anne Heerklotz, Magali Toussaint, Winnie Deuther-Conrad, Guy Bormans, Peter Brust, Klaus Kopka, Rareş-Petru Moldovan","doi":"10.1186/s41181-024-00319-2","DOIUrl":"10.1186/s41181-024-00319-2","url":null,"abstract":"<div><h3>Background</h3><p>The cannabinoid type 2 receptors (CB2R) represent a target of increasing importance in neuroimaging due to its upregulation under various neuropathological conditions. Previous evaluation of [<sup>18</sup>F]JHU94620 for the non-invasive assessment of the CB2R availability by positron emission tomography (PET) revealed favourable binding properties and brain uptake, however rapid metabolism, and generation of brain-penetrating radiometabolites have been its main limitations. To reduce the bias of CB2R quantification by blood–brain barrier (BBB)-penetrating radiometabolites, we aimed to improve the metabolic stability by developing -<i>d</i><sub>4</sub> and -<i>d</i><sub>8</sub> deuterated isotopologues of [<sup>18</sup>F]JHU94620.</p><h3>Results</h3><p>The deuterated [<sup>18</sup>F]JHU94620 isotopologues showed improved metabolic stability avoiding the accumulation of BBB-penetrating radiometabolites in the brain over time. CB2R-specific binding with <i>K</i><sub>D</sub> values in the low nanomolar range was determined across species. Dynamic PET studies revealed a CB2R-specific and reversible uptake of [<sup>18</sup>F]JHU94620-<i>d</i><sub>8</sub> in the spleen and to a local <i>h</i>CB2R(D80N) protein overexpression in the striatal region in rats.</p><h3>Conclusion</h3><p>These results support further investigations of [<sup>18</sup>F]JHU94620-<i>d</i><sub>8</sub> in pathological models and tissues with a CB2R overexpression as a prerequisite for clinical translation.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00319-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870314","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}
Shelbie Jaylene Cingoranelli, Emily E. Putnam, Jean Pierre Appiah, Jason Rider, Logan Burnett, Suzanne E. Lapi
{"title":"Production of high purity 47Sc from proton irradiation of natural vanadium targets","authors":"Shelbie Jaylene Cingoranelli, Emily E. Putnam, Jean Pierre Appiah, Jason Rider, Logan Burnett, Suzanne E. Lapi","doi":"10.1186/s41181-024-00321-8","DOIUrl":"10.1186/s41181-024-00321-8","url":null,"abstract":"<div><h3>Background</h3><p>Scandium-47 is the therapeutic counterpart to the diagnostic radionuclides, <sup>43</sup>Sc and <sup>44</sup>Sc. Together, these form elementally matched theranostic nuclide pairs, but their incorporation into radiopharmaceuticals requires developing production techniques leading to radioscandium isotopes with high chemical and radionuclidic purity. Previous <sup>47</sup>Sc production methods involved expensive, enriched titanium targets that require additional procedures for target recovery. This work investigates the irradiation of natural vanadium targets and the development of purification methods for high-purity <sup>47</sup>Sc. Natural vanadium foils were used in cyclotron target configurations. Targets were irradiated with 24 MeV protons at currents of up to 80 µA. A purification method was developed by determining the K<sub>d</sub> values of Sc, Cr, and V using MP-50 resin. The final purification method used MP-50 and CM resin columns to isolate the <sup>47</sup>Sc from <sup>nat</sup>V and co-produced <sup>51</sup>Cr. Inductively Coupled Plasma Mass Spectrometry (ICP-MS), gamma-ray spectroscopy, and a DOTA titration were used to characterize the <sup>47</sup>Sc product. </p><h3>Results</h3><p>Two cyclotron targets were designed, a small-scale target for developing a purification procedure and a high-power target for scaled-up production. The high-power target maximum current was 80 µA of 24 MeV protons. The yield for an 8 h irradiation at 80 µA of 24 MeV protons, was 128.02 ± 11.1 MBq of <sup>47</sup>Sc at End of Bombardment. The radionuclidic purity of <sup>47</sup>Sc was 99.5 ± 0.2%. The purification using MP-50 and CM columns resulted in the removal of <sup>nat</sup>V target and <sup>51</sup>Cr contaminate in the final <sup>47</sup>Sc product, with an average recovery of 72 ± 2.1% and a DOTA apparent molar activity of 7733 ± 155 MBq/µmol. ICP-MS results showed that all top-row transition metals were below the limit of detection (< 1 ppb) with the exception of Zn, which was 64.6 ± 10.3 ppb.</p><h3>Conclusions</h3><p>A high-power cyclotron target capable of withstanding a proton current of 80 µA was developed. A novel separation method was developed for isolating the <sup>47</sup>Sc from the vanadium target and the co-produced <sup>51</sup>Cr contaminate. The final product characterization resulted in a chemically and radionuclidically pure <sup>47</sup>Sc product with high recovery yields.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00321-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142844840","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}
Maija Radzina, Laura Saule, Edgars Mamis, Elina Pajuste, Ulli Koester, Thomas Elias Cocolios, Jevgenijs Proskurins, Patricija Kalnina, Rudolfs Janis Zabolockis, Kristaps Palskis, Zeynep Talip, Mikael Jensen, Charlotte Duchemin, Sarah Baatout, Kirsten Leufgen, Thierry Stora
{"title":"Novel radionuclides: demand, production and distribution for translational research in Europe","authors":"Maija Radzina, Laura Saule, Edgars Mamis, Elina Pajuste, Ulli Koester, Thomas Elias Cocolios, Jevgenijs Proskurins, Patricija Kalnina, Rudolfs Janis Zabolockis, Kristaps Palskis, Zeynep Talip, Mikael Jensen, Charlotte Duchemin, Sarah Baatout, Kirsten Leufgen, Thierry Stora","doi":"10.1186/s41181-024-00318-3","DOIUrl":"10.1186/s41181-024-00318-3","url":null,"abstract":"<div><h3>Background</h3><p>In the field of medical and scientific research, radionuclides are used to investigate various physiological and pathological processes. PRISMAP - the European medical radionuclide programme was created to bring together production facilities including intense neutron sources, an isotope mass separation facility, high-power accelerators, biomedical research institutes, and hospitals to support medical research. The aim of this article is to introduce readers with the current status of innovative radionuclides in Europe.</p><h3>Main body</h3><p> A survey was created targeting the latest trends mainly focused on the demand, the production and the distribution of non-routinely used medical radionuclides for use in research, and for pre-clinical and clinical trials. This survey has been disseminated through the PRISMAP community. 16 of 104 respondents were working in the field of radionuclide production. The data found common aspects from all producer-facility respondents: the biggest challenge for the producers is the availability of target materials, which goes hand-in-hand with their purity/enrichment grade. The results show that there are sufficient national or international distribution routes and methods established, although having reported challenges due to legislation constraints, especially for novel radionuclides.</p><h3>Conclusions</h3><p>Thanks to a questionnaire distributed by the PRISMAP consortium, the current status in radionuclides production was identified. Understanding the current status of radionuclide production is essential for assessing the continent’s capabilities and addressing the burgeoning demands for cutting-edge medical radionuclides.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00318-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142844844","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":"Production of [18F]DPA-714, [18F]fallypride and [18F]LBT-999 using iMiDEV, a fully automated microfluidic platform: towards clinical radiopharmaceutical production","authors":"Salla Lahdenpohja, Camille Piatkowski, Laurent Tanguy, Bertrand Kuhnast","doi":"10.1186/s41181-024-00315-6","DOIUrl":"10.1186/s41181-024-00315-6","url":null,"abstract":"<div><h3>Background</h3><p>Positron emission tomography is widely used to study biological processes without disrupting normal physiological functions. Traditional radiotracer synthesis and industrial market is focused on producing large batches of <sup>18</sup>F-labelled tracers, especially [<sup>18</sup>F]FDG. Accessibility to smaller quantity of diverse radiopharmaceuticals is a key to enable a more personalised approach in nuclear medicine. A novel microfluidic module, iMiDEV™, has earlier been shown to be a versatile labelling platform as it has been used in the production of Na[<sup>18</sup>F]F and various <sup>11</sup>C- and <sup>68</sup> Ga-labelled tracers. In the current study our aim was to utilise iMiDEV™ in the synthesis of fluorine-18-labelled radiotracers, specifically [<sup>18</sup>F]DPA-714, [<sup>18</sup>F]LBT-999 and [<sup>18</sup>F]fallypride.</p><h3>Results</h3><p>[<sup>18</sup>F]DPA-714, [<sup>18</sup>F]LBT-999 and [<sup>18</sup>F]fallypride have been produced in up to 24%, 12% and 11% radiochemical yield, respectively, using the microfluidics based iMiDEV™ labelling platform. Activity yields at the end of synthesis were 3.6 GBq, 2.1 GBq and 2.3 GBq, respectively. All individual synthesis steps were studied for efficient activity transfer and labelling and the optimised synthesis sequence was fully automated.</p><h3>Conclusion</h3><p>In this paper, we have demonstrated fully automated production of different <sup>18</sup>F-tracers of clinical relevance with moderate to good yields using microfluidic iMiDEV™ platform. Our work is a step towards more personalised, dose-on-demand manufacturing of PET radiopharmaceuticals.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00315-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142844843","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}