EJNMMI Radiopharmacy and Chemistry最新文献

{"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":"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 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":"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}

{"title":"First preclinical SPECT/CT imaging and biodistribution of [165Er]ErCl3 and [165Er]Er-PSMA-617","authors":"Behrad Saeedi Saghez,&nbsp;Cristina Rodríguez-Rodríguez,&nbsp;Pedro Luis Esquinas,&nbsp;Helen Merkens,&nbsp;François Bénard,&nbsp;Valery Radchenko,&nbsp;Hua Yang","doi":"10.1186/s41181-024-00312-9","DOIUrl":"10.1186/s41181-024-00312-9","url":null,"abstract":"<div><h3>Background</h3><p>¹⁶⁵Er (t_1/2 = 10.4 h, E_x-ray = 47.1 keV (59.4%) and 54.3 keV (14.3%)) is a promising radionuclide suitable for targeted Auger electron therapy of cancer. ¹⁶⁵Er can be produced at a relatively low cost, high yield, and high purity using small medical cyclotrons. As a late lanthanide, ¹⁶⁵Er is easy to label and can be used as a surrogate for other lanthanides or Ac in proof-of-concept studies. In this report, we explore the radiochemistry, in vitro, and in vivo behavior of [¹⁶⁵Er]ErCl₃ and [¹⁶⁵Er]Er-PSMA-617 to showcase the application of this radionuclide. Particularly, we report the first phantom and preclinical SPECT imaging of this radionuclide leveraging its characteristic X-ray photon emissions.</p><h3>Results</h3><p>The ¹⁶⁵Ho(p,n)¹⁶⁵Er nuclear reaction using a 13 MeV cyclotron demonstrated production yields of up to 25 ± 5 MBq. µA⁻¹ h⁻¹ at the end of the bombardment. After the purification (4.0 ± 0.5 h) using a sequential combination of cation exchange and extraction chromatography, 4-h irradiation produced up to 1.5 GBq of [¹⁶⁵Er]ErCl₃. High molar activity [¹⁶⁵Er]Er-PSMA-617 was prepared (~ 200 MBq/nmol). [¹⁶⁵Er]Er-PSMA-617 showed a Log<i>D</i>_7.4 value of -2.34 ± 0.24 meaning high hydrophilicity of the complex as expected. The stability of [¹⁶⁵Er]Er-PSMA-617 in saline, human, and mouse serum was studied and showed intact tracer after 12 h in all three cases. [¹⁶⁵Er]ErCl₃ and [¹⁶⁵Er]Er-PSMA-617 were both taken up by LNCaP cells. PSMA-617 has IC₅₀ at nanomolar range for [¹⁶⁵Er]Er-PSMA-617 in LNCaP cells. SPECT images with preclinical phantoms showed good uniformity, spatial resolution, and quantitative accuracy. SPECT/CT imaging in LNCaP tumor-bearing mice injected with [¹⁶⁵Er]Er-PSMA-617 showed high tumor uptake and quantitative accuracy when comparing the results to ex vivo biodistribution %IA/g values. Mice injected with [¹⁶⁵Er]ErCl₃ showed uptake in bone structures and excretion through both liver and kidneys.</p><h3>Conclusions</h3><p>This study demonstrated the preclinical use of ¹⁶⁵Er for the first time. Using [¹⁶⁵Er]ErCl₃ and [¹⁶⁵Er]Er-PSMA-617 as examples, the radiochemistry, cell, and animal studies showed that ¹⁶⁵Er can be used as a tool for evaluating targeted radiopharmaceuticals. The X-ray emission from ¹⁶⁵Er can be used for quantitative SPECT imaging in mice.</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/s41181-024-00312-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142844839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a homotrimeric PSMA radioligand based on the NOTI chelating platform","authors":"Sebastian Martin,&nbsp;Moritz-Valentin Schreck,&nbsp;Tobias Stemler,&nbsp;Stephan Maus,&nbsp;Florian Rosar,&nbsp;Caroline Burgard,&nbsp;Andrea Schaefer-Schuler,&nbsp;Samer Ezziddin,&nbsp;Mark D. Bartholomä","doi":"10.1186/s41181-024-00314-7","DOIUrl":"10.1186/s41181-024-00314-7","url":null,"abstract":"<div><h3>Background</h3><p>The NOTI chelating scaffold can readily be derivatized for bioconjugation without impacting its metal complexation/radiolabeling properties making it an attractive building block for the development of multimeric/-valent radiopharmaceuticals. The objective of the study was to further explore the potential of the NOTI chelating platform by preparing and characterizing homotrimeric PSMA radioconjugates in order to identify a suitable candidate for clinical translation.</p><h3>Results</h3><p>Altogether, three PSMA conjugates based on the NOTI-TVA scaffold with different spacer entities between the chelating unit and the Glu-CO-Lys PSMA binding motif were readily prepared by solid phase-peptide chemistry. Cell experiments allowed the identification of the homotrimeric conjugate <b>9</b> comprising NaI-Amc spacer with high PSMA binding affinity (IC₅₀ = 5.9 nM) and high PSMA-specific internalization (17.8 ± 2.5%) compared to the clinically used radiotracer [⁶⁸Ga]Ga-PSMA-11 with a IC₅₀ of 18.5 nM and 5.2 ± 0.2% cell internalization, respectively. All ⁶⁸Ga-labeled trimeric conjugates showed high metabolic stability in vitro with [⁶⁸Ga]Ga-<b>9</b> exhibiting high binding to human serum proteins (&gt; 95%). Small-animal PET imaging revealed a specific tumor uptake of 16.0 ± 1.3% IA g⁻¹ and a kidney uptake of 67.8 ± 8.4% IA g⁻¹ for [⁶⁸Ga]Ga-<b>9</b>. Clinical PET imaging allowed identification of all lesions detected by [⁶⁸Ga]Ga-PSMA-11 together with a prolonged blood circulation as well as a significantly lower kidney and higher liver uptake of [⁶⁸Ga]Ga-<b>9</b> compared to [⁶⁸Ga]Ga-PSMA-11.</p><h3>Conclusions</h3><p>Trimerization of the Glu-CO-Lys binding motif for conjugate <b>9</b> resulted in a ~ threefold higher binding affinity and cellular uptake as well as in an altered biodistribution profile compared to the control [⁶⁸Ga]Ga-PSMA-11 due to its intrinsic high binding to serum proteins. To fully elucidate its biodistribution, future studies in combination with long-lived radionuclides, such as ⁶⁴Cu, are warranted. Its prolonged biological half-life and favorable tumor-to-kidney ratio make this homotrimeric conjugate also a potential candidate for future radiotherapeutic applications in combination with therapeutic radionuclides such as ⁶⁷Cu.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00314-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805712","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":"An ACE2 PET imaging agent derived from 18F/Cl exchange of MLN-4760 under phase transfer catalysis","authors":"Pan Zhou,&nbsp;Kai Ning,&nbsp;Shuai Xue,&nbsp;Qingqing Li,&nbsp;Danni Li,&nbsp;Haijun Yang,&nbsp;Zeying Liang,&nbsp;Rou Li,&nbsp;Jian Yang,&nbsp;Xiao Li,&nbsp;Lan Zhang","doi":"10.1186/s41181-024-00316-5","DOIUrl":"10.1186/s41181-024-00316-5","url":null,"abstract":"<div><h3>Background</h3><p>Angiotensin-converting enzyme-2 (ACE2) acts as a key regulatory molecule and important therapeutic target in the pathological remodeling of numerous organs and diseases. In this study, a rapid, simple, and efficient synthetic route with a catalytic, ¹⁸F-for-Cl (¹⁸F/Cl) exchange scheme was designed for the preparation of ¹⁸F-labeled MLN-4760, and its targeting ability was investigated in a humanized ACE2 mouse model.</p><h3>Results</h3><p>A novel ¹⁸F-labeled MLN-4760 radioligand, abbreviated as ¹⁸F-MLN-4760, was successfully synthesized by the ¹⁸F/Cl exchange-labeling, and was purified by SepPak C18 columns with a radiochemical yield of 30% and a radiochemical purity of 29.89%. Target distribution of ¹⁸F-MLN-4760 in several organs with high ACE2 expression was observed by PET imaging with good stability over 120 min. The biodistribution data showed that the uptake of ¹⁸F-MLN-4760 in ACE2-overexpressing organs and tissues was highly specific, and immunohistochemistry confirmed the same results of ACE2 expression and biodistribution in the major organs (heart, liver, lungs, and kidneys). There was a good correlation between the uptake in the organs with high ACE2 expression and ACE2 expression levels (<i>r</i> = 0.935).</p><h3>Conclusion</h3><p>¹⁸F-MLN-4760 was successfully synthesized via ¹⁸F/Cl exchange under phase transfer catalysis, and served as a potential probe for ACE2-targeted PET imaging.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00316-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142761907","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 proof-of-concept study to investigate the radiolabelling of human mesenchymal and hematopoietic stem cells with [89Zr]Zr-Df-Bz-NCS","authors":"Maryke Kahts,&nbsp;Juanita Mellet,&nbsp;Chrisna Durandt,&nbsp;Kinosha Moodley,&nbsp;Beverley Summers,&nbsp;Thomas Ebenhan,&nbsp;Jan Rijn Zeevaart,&nbsp;Omer Aras,&nbsp;Michael S. Pepper","doi":"10.1186/s41181-024-00311-w","DOIUrl":"10.1186/s41181-024-00311-w","url":null,"abstract":"<div><h3>Background</h3><p>The transplantation of hematopoietic stem and progenitor cells (HSPCs) or mesenchymal stromal/stem cells (MSCs) for the treatment of a wide variety of diseases has been studied extensively. A challenge with cell-based therapies is that migration to and retention at the target site is often difficult to monitor and quantify. Zirconium-89 (⁸⁹Zr) is a positron-emitting radionuclide with a half-life of 3.3 days, which allows long-term cell tracking. Para-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) is the chelating agent of choice for ⁸⁹Zr-cell surface labelling. We utilised a shortened labelling method, thereby avoiding a 30–60-min incubation step for [⁸⁹Zr]Zr-Df-Bz-NCS chelation, to radiolabel HSPCs and MSCs with zirconium-89.</p><h3>Results</h3><p>Three ⁸⁹Zr-MSC labelling attempts were performed. High labelling efficiencies (81.30 and 87.30%) and relatively good labelling yields (59.59 and 67.00%) were achieved with the use of a relatively larger number of MSCs (4.425 and 3.855 million, respectively). There was no significant decrease in MSC viability after ⁸⁹Zr-labeling (<i>p</i> = 0.31). This labelling method was also translatable to prepare ⁸⁹Zr-HSPC; preliminary data from one preparation indicated high ⁸⁹Zr-HSPC labelling efficiency (88.20%) and labelling yield (71.06%), as well as good HSPC viability after labelling (68.65%).</p><h3>Conclusions</h3><p>Successful ⁸⁹Zr-MSC and ⁸⁹Zr-HSPC labelling was achieved, which underlines the prospects for in vivo cell tracking studies with positron emission tomography. In vitro investigations with larger sample sizes and preclinical studies are recommended.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00311-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737037","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}