EJNMMI Radiopharmacy and Chemistry最新文献

{"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}

{"title":"Optimized chelator and nanoparticle strategies for high-activity 103Pd-loaded biodegradable brachytherapy seeds","authors":"Emanuel Sporer,&nbsp;Claire Deville,&nbsp;Natan J. W. Straathof,&nbsp;Linda M. Bruun,&nbsp;Ulli Köster,&nbsp;Mikael Jensen,&nbsp;Thomas L. Andresen,&nbsp;Paul J. Kempen,&nbsp;Jonas R. Henriksen,&nbsp;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 ¹⁰³Pd-labeled palladium-gold alloy nanoparticles ([¹⁰³Pd]PdAuNPs). These were prepared by combining [¹⁰³Pd]PdH₂Cl₄ and AuHCl₄, 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, [¹⁰³Pd]Pd-SSIB was prepared by conjugating the [16]aneS₄ chelator with lipophilic sucrose septaisobutyrate (SSIB) followed by complexation with [¹⁰³Pd]PdH₂Cl₄ (RCY = 99%) and mixed with LOIB:EtOH. [¹⁰³Pd]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 ¹⁰³Pd 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]aneS₄ 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}

{"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,&nbsp;Mudasir Maqbool,&nbsp;Rodrigo Teodoro,&nbsp;Friedrich-Alexander Ludwig,&nbsp;Anne Heerklotz,&nbsp;Magali Toussaint,&nbsp;Winnie Deuther-Conrad,&nbsp;Guy Bormans,&nbsp;Peter Brust,&nbsp;Klaus Kopka,&nbsp;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 [¹⁸F]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>₄ and -<i>d</i>₈ deuterated isotopologues of [¹⁸F]JHU94620.</p><h3>Results</h3><p>The deuterated [¹⁸F]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>_D values in the low nanomolar range was determined across species. Dynamic PET studies revealed a CB2R-specific and reversible uptake of [¹⁸F]JHU94620-<i>d</i>₈ 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 [¹⁸F]JHU94620-<i>d</i>₈ 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}

{"title":"Production of high purity 47Sc from proton irradiation of natural vanadium targets","authors":"Shelbie Jaylene Cingoranelli,&nbsp;Emily E. Putnam,&nbsp;Jean Pierre Appiah,&nbsp;Jason Rider,&nbsp;Logan Burnett,&nbsp;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, ⁴³Sc and ⁴⁴Sc. 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 ⁴⁷Sc 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 ⁴⁷Sc. 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_d values of Sc, Cr, and V using MP-50 resin. The final purification method used MP-50 and CM resin columns to isolate the ⁴⁷Sc from ^natV and co-produced ⁵¹Cr. Inductively Coupled Plasma Mass Spectrometry (ICP-MS), gamma-ray spectroscopy, and a DOTA titration were used to characterize the ⁴⁷Sc 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 ⁴⁷Sc at End of Bombardment. The radionuclidic purity of ⁴⁷Sc was 99.5 ± 0.2%. The purification using MP-50 and CM columns resulted in the removal of ^natV target and ⁵¹Cr contaminate in the final ⁴⁷Sc 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 (&lt; 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 ⁴⁷Sc from the vanadium target and the co-produced ⁵¹Cr contaminate. The final product characterization resulted in a chemically and radionuclidically pure ⁴⁷Sc 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}

{"title":"Novel radionuclides: demand, production and distribution for translational research in Europe","authors":"Maija Radzina,&nbsp;Laura Saule,&nbsp;Edgars Mamis,&nbsp;Elina Pajuste,&nbsp;Ulli Koester,&nbsp;Thomas Elias Cocolios,&nbsp;Jevgenijs Proskurins,&nbsp;Patricija Kalnina,&nbsp;Rudolfs Janis Zabolockis,&nbsp;Kristaps Palskis,&nbsp;Zeynep Talip,&nbsp;Mikael Jensen,&nbsp;Charlotte Duchemin,&nbsp;Sarah Baatout,&nbsp;Kirsten Leufgen,&nbsp;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,&nbsp;Camille Piatkowski,&nbsp;Laurent Tanguy,&nbsp;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 ¹⁸F-labelled tracers, especially [¹⁸F]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[¹⁸F]F and various ¹¹C- and ⁶⁸ Ga-labelled tracers. In the current study our aim was to utilise iMiDEV™ in the synthesis of fluorine-18-labelled radiotracers, specifically [¹⁸F]DPA-714, [¹⁸F]LBT-999 and [¹⁸F]fallypride.</p><h3>Results</h3><p>[¹⁸F]DPA-714, [¹⁸F]LBT-999 and [¹⁸F]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 ¹⁸F-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}

{"title":"A comparison of routine [68Ga]Ga-PSMA-11 preparation using Locametz and Illuccix kits","authors":"Ivan E. Wang,&nbsp;Luke J. Morrissette,&nbsp;Ka Kit Wong,&nbsp;Allen F. Brooks,&nbsp;Marianna Dakanali,&nbsp;Peter J. H. Scott","doi":"10.1186/s41181-024-00317-4","DOIUrl":"10.1186/s41181-024-00317-4","url":null,"abstract":"<div><h3>Background</h3><p>Approval of Locametz and Illuccix kits for the manufacture of [⁶⁸Ga]Ga-PSMA-11 (gallium Ga68 gozetotide), a PET imaging agent for prostate cancer, as well as the corresponding therapeutic ([¹⁷⁷Lu]Lu-PSMA-617 Pluvicto), has led to a rapid increase in demand for [⁶⁸Ga]Ga-PSMA-11 PET imaging. Radiopharmaceutical manufacturers, using ⁶⁸Ge/⁶⁸Ga generators, may decide to adopt Locametz and/or Illuccix kits, which requires a comparison to select the most suitable kit for day-to-day use. The objective of this article is to compare both kits and provide guidance for selecting one for routine use, as well as evaluate labeling consistency of both kits during routine production. Additionally, we report our experience during 1.5 years of daily [⁶⁸Ga]Ga-PSMA-11 production at our facility using both kits.</p><h3>Results</h3><p>Locametz (n = 181) and Illuccix (n = 256) kits were prepared using non-silicone coated and silicone-coated needles with ⁶⁸Ga activities ranging from 0.53 to 3.16 GBq, with a failure rate of 1 in 128 runs for both kits. With Locametz, a 3.7 GBq generator and 10-min incubation at room temperature gave doses that passed quality control (QC) testing. Use of non-silicone coated needles in the process led to solution discoloration, and QC failure. Additionally, lack of vial inversion led to inconsistent labeling, which improved with subsequent vial agitation. For Illuccix, addition of the acetate buffer to the precursor vial prior to adding the [⁶⁸Ga]GaCl₃ simplifies the workflow. The maximum tolerated activity was 1.85 GBq. Lack of vial inversion led to failures, which were rectified by agitating the vial to properly incorporate the acetate solution with the generator eluate.</p><h3>Conclusions</h3><p>Both kits benefited from using a syringe pump to elute the ⁶⁸Ge/⁶⁸Ga generator, vial agitation, and longer length/smaller bore silicone coated needles. Both kits have similar workflows, comparable QC outcomes, and result in equivalent clinical images. Thus, the decision between kits will ultimately be determined by production preferences. Since radiopharmacies have an established “kit-based” workflow, Locametz kits with higher allowed activities and longer shelf-life may offer benefits. Conversely, more traditional PET manufacturing facilities might benefit from using Illuccix kits due to compatibility with cyclotron-produced [⁶⁸Ga]GaCl₃ allowing for kit batching. Ultimately, the commercial availability of 2 approved kits for production of [⁶⁸Ga]Ga-PSMA-11 PET has facilitated ready access to this important new imaging agent.</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/s41181-024-00317-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142844842","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":"[89Zr]Zr-DFO-TOC: a novel radiopharmaceutical for PET imaging of somatostatin receptor positive neuroendocrine tumors","authors":"Alexis M. Sanwick,&nbsp;Katherine N. Haugh,&nbsp;Evan J. Williams,&nbsp;Kala A. Perry,&nbsp;Nikki A. Thiele,&nbsp;Ivis F. Chaple","doi":"10.1186/s41181-024-00320-9","DOIUrl":"10.1186/s41181-024-00320-9","url":null,"abstract":"<div><h3>Background</h3><p>Neuroendocrine tumors (NETs) are clinically diverse types of tumors that can arise anywhere in the body. Previous studies have shown that somatostatin receptors (SSTRs) are overexpressed on NET cell membranes relative to healthy tissue, allowing for tumor targeting through radiolabeled somatostatin analogs (SSAs). This work aims to develop a novel ⁸⁹Zr-labeled tracer incorporating the SSA, octreotide (TOC), for positron emission tomography (PET) imaging of SSTR + NETs and predictive dosimetry calculations, leveraging the excellent nuclear (t_½ = 3.27 days, β+ = 22.3%, β⁺_avg = 395.5 keV) and chemical characteristics (+ 4 oxidation state, preferential coordination number of 7/8, favorable aqueous chemistry) of ⁸⁹Zr. In combination with ⁸⁹Zr, the known radiochemistry with the chelator deferoxamine (DFO) gives reason to believe that this radiopharmaceutical incorporating an octreotide conjugate will be successful in studying the suitability of detecting SSTR + NETs.</p><h3>Results</h3><p>Radiochemical tracer assessment indicated that amounts as low as 0.1 nmol DFO-TOC can be effectively radiolabeled with ⁸⁹Zr, while maintaining ≥ 95% radiochemical yield. The stability of the compound was found to maintain radiochemical yields of 89.6% and 88.7% on the benchtop and in mouse serum, respectively, after 9 days. Receptor binding and competitive receptor blocking assays compared AR42J (high SSTR expression), PC-3 (moderate SSTR expression), and PANC-1 (minimal SSTR expression) cell lines at time points up to 6 days. In vitro studies demonstrated highest uptake in AR42J cells, and statistically significant differences in tracer uptake were seen after 1 h. Internalization assays showed maximum internalization after 3 h for all cell lines.</p><h3>Conclusions</h3><p>In this work, [⁸⁹Zr]Zr-DFO-TOC was synthesized with radiochemical yields ≥ 95% and was found to remain stable in vitro at extended time points. In vitro cell studies demonstrated a statistically significant difference between receptor binding and blocking experiments. The development of this work shows potential to positively impact patient care through the predictive dosimetry calculations for the FDA-approved therapeutic agent [¹⁷⁷Lu]Lu-DOTA-TATE, while allowing for imaging at extended timepoints and should be studied further.</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/s41181-024-00320-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142844841","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}