Nuclear medicine and biology最新文献

{"title":"Development of a CCR2 targeted 18F-labeled radiotracer for atherosclerosis imaging with PET","authors":"Xiaohui Zhang ,&nbsp;Lin Qiu ,&nbsp;Debbie H. Sultan ,&nbsp;Hannah P. Luehmann ,&nbsp;Yanbo Yu ,&nbsp;Xiuli Zhang ,&nbsp;Gyu Seong Heo ,&nbsp;Alexandria Li ,&nbsp;Divangana Lahad ,&nbsp;Shinji Rho ,&nbsp;Zhude Tu ,&nbsp;Yongjian Liu","doi":"10.1016/j.nucmedbio.2024.108893","DOIUrl":"10.1016/j.nucmedbio.2024.108893","url":null,"abstract":"<div><p>Atherosclerosis is a chronic inflammatory disease and the leading cause of morbidity and mortality worldwide. C<img>C motif chemokine ligand 2 and its corresponding cognate receptor 2 (CCL2/CCR2) signaling has been implicated in regulating monocyte recruitment and macrophage polarization during inflammatory responses that plays a pivotal role in atherosclerosis initiation and progression. In this study, we report the design and synthesis of a novel ¹⁸F radiolabeled small molecule radiotracer for CCR2-targeted positron emission tomography (PET) imaging in atherosclerosis. The binding affinity of this radiotracer to CCR2 was evaluated <em>via in vitro</em> binding assay using CCR2+ membrane and cells. <em>Ex vivo</em> biodistribution was carried out in wild type mice to assess radiotracer pharmacokinetics. CCR2 targeted PET imaging of plaques was performed in two murine atherosclerotic models. The sensitive detection of atherosclerotic lesions highlighted the potential of this radiotracer for CCR2 targeted PET and warranted further optimization.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"130 ","pages":"Article 108893"},"PeriodicalIF":3.1,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139953595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biodistribution study of 211Pb progeny released from intravenously applied 223Ra labelled TiO2 nanoparticles in a mouse model","authors":"Michal Sakmár ,&nbsp;Ján Kozempel ,&nbsp;Jan Kučka ,&nbsp;Tereza Janská ,&nbsp;Matěj Štíbr ,&nbsp;Martin Vlk ,&nbsp;Luděk Šefc","doi":"10.1016/j.nucmedbio.2024.108890","DOIUrl":"10.1016/j.nucmedbio.2024.108890","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Targeted alpha therapy is one of the most powerful therapeutical modalities available in nuclear medicine. It's therapeutic potency is based on the nuclides that emit one or several alpha particles providing strong and highly localized therapeutic effects. However, some of these radionuclides, like &lt;em&gt;e.g.&lt;/em&gt; &lt;sup&gt;223&lt;/sup&gt;Ra or &lt;sup&gt;225&lt;/sup&gt;Ac decay in cascades, where the radioactive progeny originating from the consecutive alpha-decays may leave the original vector and cause unwanted irradiation of non-target organs. This progeny, even if partially retained in target tissues by internalization processes, typically do not follow the fate of originally targeted radiopharmaceutical and potentially spread over body following their own biodistribution. In this study we aimed to estimate &lt;sup&gt;211&lt;/sup&gt;Pb/&lt;sup&gt;211&lt;/sup&gt;Bi progeny fate from the &lt;sup&gt;223&lt;/sup&gt;Ra surface-labelled TiO&lt;sub&gt;2&lt;/sub&gt; nanoparticles &lt;em&gt;in vitro&lt;/em&gt; and the fate of &lt;sup&gt;211&lt;/sup&gt;Pb &lt;em&gt;in vivo&lt;/em&gt; in a mice model.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;&lt;em&gt;In vitro&lt;/em&gt; stability studies have shown significant differences between the release of the mother &lt;sup&gt;223&lt;/sup&gt;Ra and its progeny (&lt;sup&gt;211&lt;/sup&gt;Pb, &lt;sup&gt;211&lt;/sup&gt;Bi) in all the biological matrices that have been tested. The lowest released activities were measured in saline, resulting in less than 5 % of released activity for all nuclides. Contrary to that, the highest released activity of &lt;sup&gt;223&lt;/sup&gt;Ra of up to 10 % within 48 h was observed in 5 % solution of albumin. The released activity of its progeny; the &lt;sup&gt;211&lt;/sup&gt;Pb and &lt;sup&gt;211&lt;/sup&gt;Bi was in the range of 20–40 % in this test medium. Significantly higher released activities of &lt;sup&gt;211&lt;/sup&gt;Pb and &lt;sup&gt;211&lt;/sup&gt;Bi compared to &lt;sup&gt;223&lt;/sup&gt;Ra by at least 10 % was observed in each biological medium, except saline, where no significant differences were observed. The &lt;em&gt;in vivo&lt;/em&gt; biodistribution studies results in a mice model, show similar pattern, where it was found that even after accumulation of nanoparticles in target tissues, approximately 10 % of &lt;sup&gt;211&lt;/sup&gt;Pb is continuously released into the blood stream within 24 h, followed by its natural accumulation in kidneys.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;This study confirms our assumption that the progeny formed in a chain alpha decay of a certain nuclide, in this case the &lt;sup&gt;223&lt;/sup&gt;Ra, can be released from its original vector, leave the target tissue, relocate and could be deposited in non-target organs. We did not observe complete progeny wash-out from its original target tissues in our model. This indicates strong dependence of the progeny hot atom fate after its release from the original radiopharmaceutical preparation on multiple factors, like their internalization and retention in cells, cell membranes, extracellular matrices, protein binding, &lt;em&gt;etc.&lt;/em&gt; We hypothesize, that also the primary tumour or metastasis size, their metabolic activity may significant","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"130 ","pages":"Article 108890"},"PeriodicalIF":3.1,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139925440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in the development of radiopharmaceuticals for nuclear medicine applications in the treatment of bone metastases","authors":"Michael R. Dyer ,&nbsp;Zhenghan Jing ,&nbsp;Kathleen Duncan ,&nbsp;Jacqueline Godbe ,&nbsp;Monica Shokeen","doi":"10.1016/j.nucmedbio.2024.108879","DOIUrl":"10.1016/j.nucmedbio.2024.108879","url":null,"abstract":"<div><p>Bone metastases are a painful and complex condition that overwhelmingly impacts the prognosis and quality of life of cancer patients. Over the years, nuclear medicine has made remarkable progress in the diagnosis and management of bone metastases. This review aims to provide a comprehensive overview of the recent advancements in nuclear medicine for the diagnosis and management of bone metastases. Furthermore, the review explores the role of targeted radiopharmaceuticals in nuclear medicine for bone metastases, focusing on radiolabeled molecules that are designed to selectively target biomarkers associated with bone metastases, including osteocytes, osteoblasts, and metastatic cells. The applications of radionuclide-based therapies, such as strontium-89 (Sr-89) and radium-223 (Ra-223), are also discussed. This review also highlights the potential of theranostic approaches for bone metastases, enabling personalized treatment strategies based on individual patient characteristics. Importantly, the clinical applications and outcomes of nuclear medicine in osseous metastatic disease are discussed. This includes the assessment of treatment response, predictive and prognostic value of imaging biomarkers, and the impact of nuclear medicine on patient management and outcomes. The review identifies current challenges and future perspectives on the role of nuclear medicine in treating bone metastases. It addresses limitations in imaging resolution, radiotracer availability, radiation safety, and the need for standardized protocols. The review concludes by emphasizing the need for further research and advancements in imaging technology, radiopharmaceutical development, and integration of nuclear medicine with other treatment modalities. In summary, advancements in nuclear medicine have significantly improved the diagnosis and management of osseous metastatic disease and future developements in the integration of innovative imaging modalities, targeted radiopharmaceuticals, radionuclide production, theranostic approaches, and advanced image analysis techniques hold great promise in improving patient outcomes and enhancing personalized care for individuals with bone metastases.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"130 ","pages":"Article 108879"},"PeriodicalIF":3.1,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139677253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a novel hexadentate 1,2-hydroxypyridinone-based acyclic chelate, HOPO-O6-C4, for 43Sc/47Sc, 68Ga, and 45Ti radiopharmaceuticals","authors":"Imma Carbo-Bague ,&nbsp;Shefali Saini ,&nbsp;Shelbie J. Cingoranelli ,&nbsp;Patrick R.W.J. Davey ,&nbsp;Marianna Tosato ,&nbsp;Suzanne E. Lapi ,&nbsp;Caterina F. Ramogida","doi":"10.1016/j.nucmedbio.2023.108872","DOIUrl":"10.1016/j.nucmedbio.2023.108872","url":null,"abstract":"<div><h3>Introduction</h3><p>Chelators play a crucial role in the development of metal-based radiopharmaceuticals, and with the continued interest in ⁶⁸Ga and increasing availability of new radiometals such as ⁴³Sc/⁴⁷Sc and ⁴⁵Ti, there is a growing demand for tailored chelators that can form stable complexes with these metals. This work reports the synthesis and characterization of a hexadentate tris-1,2-hydroxypyridonone chelator HOPO-O₆-C4 and its in vitro and in vivo evaluation with the above mentioned radiometals.</p></div><div><h3>Methods</h3><p>To investigate the affinity of HOPO-O₆-C4, macroscopic studies were performed with Sc³⁺, and Ga³⁺ followed by DFT structural optimization of the Sc³⁺, Ga³⁺ and Ti⁴⁺ complexes. Further tracer studies with ⁴³Sc (and ⁴⁷Sc), ⁴⁵Ti, and ⁶⁸Ga were performed to determine the potential for positron emission tomography (PET) imaging with these complexes. In vitro stability studies followed by in vivo imaging and biodistribution studies were performed to understand the kinetic stability of the resultant radiometal-complexes of HOPO-O₆-C4.</p></div><div><h3>Results</h3><p>Promising radiolabeling results with HOPO-O₆-C4 were obtained with ⁴³Sc, ⁴⁷Sc, ⁴⁵Ti, and ⁶⁸Ga radionuclides; rapid radiolabeling was observed at 37 °C and pH 7 in under 30-min. Apparent molar activity measurements were performed for radiolabeling of HOPO-O₆-C4 with ⁴³Sc (4.9 ± 0.26 GBq/μmol), ⁴⁷Sc (1.58 ± 0.01 GBq/μmol), ⁴⁵Ti (11.5 ± 1.6 GBq/μmol) and ⁶⁸Ga (5.74 ± 0.7 GBq/μmol), respectively. Preclinical in vivo imaging studies resulted in promising results with [⁶⁸Ga]Ga-HOPO-O₆-C4 indicating a rapid clearance through hepatic excretion route and no decomplexation whereas [⁴³Sc]Sc-HOPO-O₆-C4, [⁴⁷Sc]Sc-HOPO-O₆-C4 and [⁴⁵Ti]Ti-HOPO-O₆-C4 showed modest and significant evidence of decomplexation, respectively.</p></div><div><h3>Conclusions</h3><p>The tris-1,2-HOPO chelator HOPO-O₆-C4 is a promising scaffold for elaboration into a ⁶⁸Ga- based radiopharmaceutical.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"128 ","pages":"Article 108872"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805123006005/pdfft?md5=7dfc517b2bee6fa2a22a6c9b5e0ee960&pid=1-s2.0-S0969805123006005-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138988763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction of a fatty acid chain modification to prolong circulatory half-life of a radioligand towards glucose-dependent insulinotropic polypeptide receptor","authors":"Amina Khalil ,&nbsp;Sona Hakhverdyan ,&nbsp;Pierre Cheung ,&nbsp;Martin Bossart ,&nbsp;Michael Wagner ,&nbsp;Olof Eriksson ,&nbsp;Irina Velikyan","doi":"10.1016/j.nucmedbio.2024.108876","DOIUrl":"10.1016/j.nucmedbio.2024.108876","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;The beneficial role of glucose-dependent insulinotropic polypeptide receptor (GIPR) in weight control and maintaining glucose levels has led to the development of several multi-agonistic peptide drug candidates, targeting GIPR and glucagon like peptide 1 receptor (GLP1R) and/or the glucagon receptor (GCGR). The &lt;em&gt;in vivo&lt;/em&gt; quantification of target occupancy by these drugs would accelerate the development of new drug candidates. The aim of this study was to evaluate a novel peptide (GIP1234), based on previously reported ligand DOTA-GIP-C803, modified with a fatty acid moiety to prolong its blood circulation. It would allow higher target tissue exposure and consequently improved peptide uptake as well as &lt;em&gt;in vivo&lt;/em&gt; PET imaging and quantification of GIPR occupancy by novel drugs of interest.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;p&gt;A 40 amino acid residue peptide (GIP1234) was synthesized based on DOTA-GIP-C803, in turn based on the sequences of endogenous GIP and Exendin-4 with specific amino acid modifications to obtain GIPR selectivity. A palmitoyl fatty acid chain was furthermore added at Lys14 &lt;em&gt;via&lt;/em&gt; a glutamic acid linker to prolong its blood circulation time by the interaction with albumin. GIP1234 was conjugated with a DOTA chelator at the C-terminal cysteine residue to achieve &lt;sup&gt;68&lt;/sup&gt;Ga radiolabeling. The resulting PET probe, [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-GIP1234 was evaluated for receptor binding specificity and selectivity using HEK293 cells transfected with human GIPR, GLP1R, or GCGR. Blocking experiments with tirzepatide (2 μM) were conducted using huGIPR HEK293 cells to investigate binding specificity. &lt;em&gt;Ex vivo&lt;/em&gt; and &lt;em&gt;in vivo&lt;/em&gt; organ distribution of [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-GIP1234 was studied in rats and a pig in comparison to [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-C803-GIP. Binding of [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-GIP1234 to albumin was assessed &lt;em&gt;in situ&lt;/em&gt; using polyacrylamide gel electrophoresis (PAGE). The stability was tested in formulation buffer and rat blood plasma.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;[&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-GIP1234 was synthesized with non-decay corrected radiochemical yield of 88 ± 3.7 % and radiochemical purity of 97.8 ± 0.8 %. The molar activity for the radiotracer was 8.1 ± 1.1 MBq/nmol. [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-GIP1234 was stable and maintained affinity to huGIPR HEK293 cells (dissociation constant (K&lt;sub&gt;d&lt;/sub&gt;) = 40 ± 12.5 nM). The binding of [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-GIP1234 to huGCGR and huGLP1R cells was insignificant. Pre-incubation of huGIPR HEK293 cell sections with tirzepatide resulted in the decrease of [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-GIP1234 binding by close to 90 %. [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-GIP1234 displayed slow blood clearance in pigs with SUV = 3.5 after 60 min. Blood retention of the tracer in rat was 2-fold higher than that of [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-C803-GIP. [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-DOTA-GIP1234 also demonstrated strong liver uptake in both pig and rat combined wi","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"128 ","pages":"Article 108876"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000027/pdfft?md5=783badf7748ed93be5ab92627c462a53&pid=1-s2.0-S0969805124000027-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139422085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of F-537-Tetrazine in a model for brain pretargeting imaging. Comparison to N-(3-[18F] fluoro-5-(1,2,4,5-tetrazin-3-yl)benzyl)propan-1-amine","authors":"Vladimir Shalgunov ,&nbsp;Sara Lopes van den Broek ,&nbsp;Ida Vang Andersen ,&nbsp;Nakul R. Raval ,&nbsp;Gabriela Schäfer ,&nbsp;Matthias Barz ,&nbsp;Matthias M. Herth ,&nbsp;Umberto M. Battisti","doi":"10.1016/j.nucmedbio.2024.108877","DOIUrl":"10.1016/j.nucmedbio.2024.108877","url":null,"abstract":"<div><p>Brain pretargeted nuclear imaging for the diagnosis of various neurodegenerative diseases is a quickly developing field. The tetrazine ligation is currently the most explored approach to achieve this goal due to its remarkable properties. In this work, we evaluated the performance of F-537-Tetrazine, previously developed by Biogen, and N-(3-[¹⁸F]fluoro-5-(1,2,4,5-tetrazin-3-yl)benzyl)propan-1-amine, previously developed in our group, thereby allowing for the direct comparison of these two imaging probes. The evaluation included synthesis, radiolabeling and a comparison of the physicochemical properties of the compounds. Furthermore, their performance was evaluated by in vitro and in vivo pretargeting models. This study indicated that N-(3-[¹⁸F] fluoro-5-(1,2,4,5-tetrazin-3-yl)benzyl)propan-1-amine might be more suited for brain pretargeted imaging.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"128 ","pages":"Article 108877"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000039/pdfft?md5=1315374ddcc052a792cf4cd244f54294&pid=1-s2.0-S0969805124000039-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139423039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"64Cu production via the 68Zn(p,nα)64Cu nuclear reaction: An untapped, cost-effective and high energy production route","authors":"Bryce J.B. Nelson ,&nbsp;Samantha Leier ,&nbsp;John Wilson ,&nbsp;Melinda Wuest ,&nbsp;Jonathan Doupe ,&nbsp;Jan D. Andersson ,&nbsp;Frank Wuest","doi":"10.1016/j.nucmedbio.2024.108875","DOIUrl":"10.1016/j.nucmedbio.2024.108875","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;Copper-64 (&lt;sup&gt;64&lt;/sup&gt;Cu, t&lt;sub&gt;1/2&lt;/sub&gt; = 12.7 h) is a positron emitter well suited for theranostic applications with beta-emitting &lt;sup&gt;67&lt;/sup&gt;Cu for targeted molecular imaging and radionuclide therapy. The present work aims to evaluate the radionuclidic purity and radiochemistry of &lt;sup&gt;64&lt;/sup&gt;Cu produced via the &lt;sup&gt;68&lt;/sup&gt;Zn(p,nα)&lt;sup&gt;64&lt;/sup&gt;Cu nuclear reaction. Macrocyclic chelators DOTA, NOTA, TETA, and prostate-specific membrane antigen ligand PSMA I&amp;T were radiolabeled with purified &lt;sup&gt;64&lt;/sup&gt;Cu and tested for in vitro stability. [&lt;sup&gt;64&lt;/sup&gt;Cu]Cu-PSMA I&amp;T was used to demonstrate in vivo PET imaging using &lt;sup&gt;64&lt;/sup&gt;Cu synthesized via the &lt;sup&gt;68&lt;/sup&gt;Zn(p,nα)&lt;sup&gt;64&lt;/sup&gt;Cu production route and its suitability as a theranostic imaging partner alongside &lt;sup&gt;67&lt;/sup&gt;Cu therapy.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;&lt;sup&gt;64&lt;/sup&gt;Cu was produced on a 24 MeV TR-24 cyclotron at a beam energy of 23.5 MeV and currents up to 70 μA using 200 mg &lt;sup&gt;68&lt;/sup&gt;Zn encapsulated within an aluminum‑indium-graphite sealed solid target assembly. &lt;sup&gt;64&lt;/sup&gt;Cu semi-automated purification was performed using a NEPTIS Mosaic-LC synthesis unit employing CU, TBP, and TK201 (TrisKem) resins. Radionuclidic purity was measured by HPGe gamma spectroscopy, while ICP-OES assessed elemental purity. Radiolabeling was performed with NOTA at room temperature and DOTA, TETA, and PSMA I&amp;T at 95 °C. &lt;sup&gt;64&lt;/sup&gt;Cu incorporation was studied by radio-TLC. &lt;sup&gt;64&lt;/sup&gt;Cu in vitro stability of [&lt;sup&gt;64&lt;/sup&gt;Cu]Cu-NOTA, [&lt;sup&gt;64&lt;/sup&gt;Cu]Cu-DOTA, [&lt;sup&gt;64&lt;/sup&gt;Cu]Cu-TETA, and [&lt;sup&gt;64&lt;/sup&gt;Cu]Cu-PSMA I&amp;T was assessed at 37 °C from 0 to 72 h in human blood serum. Preclinical PET imaging was performed at 1, 24, and 48 h post-injection with [&lt;sup&gt;64&lt;/sup&gt;Cu]Cu-PSMA I&amp;T in LNCaP tumor-bearing mice and compared with [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-PSMA I&amp;T.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Maximum purified activity of 4.9 GBq [&lt;sup&gt;64&lt;/sup&gt;Cu]CuCl&lt;sub&gt;2&lt;/sub&gt; was obtained in 5 mL of pH 2–3 solution, with 2.9 GBq &lt;sup&gt;64&lt;/sup&gt;Cu concentrated in 0.5 mL. HPGe gamma spectroscopy of purified &lt;sup&gt;64&lt;/sup&gt;Cu detected &lt;0.3 % co-produced &lt;sup&gt;67&lt;/sup&gt;Cu at EOB with no other radionuclidic impurities. ICP-OES elemental analysis determined &lt;1 ppm Al, Zn, In, Fe, and Cu in the [&lt;sup&gt;64&lt;/sup&gt;Cu]CuCl&lt;sub&gt;2&lt;/sub&gt; product. NOTA, DOTA, TETA, and PSMA I&amp;T were radiolabeled with &lt;sup&gt;64&lt;/sup&gt;Cu, resulting in maximum molar activities of 164 ± 6 GBq/μmol, 155 ± 31 GBq/μmol, 266 ± 34 GBq/μmol, and 117 ± 2 GBq/μmol, respectively. PET imaging in PSMA-expressing LNCaP xenografts resulted in high tumor uptake (SUV&lt;sub&gt;mean&lt;/sub&gt; = 1.65 ± 0.1) using [&lt;sup&gt;64&lt;/sup&gt;Cu]Cu-PSMA I&amp;T, while [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-PSMA I&amp;T yielded an SUV&lt;sub&gt;mean&lt;/sub&gt; of 0.76 ± 0.14 after 60 min post-injection.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;&lt;sup&gt;64&lt;/sup&gt;Cu was purified in a small volume amenable for radiolabeling, with yields suitable for preclinical and c","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"128 ","pages":"Article 108875"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000015/pdfft?md5=9350690548ff58e91789b923da52daf5&pid=1-s2.0-S0969805124000015-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139374217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging diabetic cardiomyopathy in a type 1 diabetic rat model using 18F-FEPPA PET","authors":"Hsin-Hua Hsieh ,&nbsp;Pei-An Chu ,&nbsp;Yu-Hsin Lin ,&nbsp;Yu-Chieh Jill Kao ,&nbsp;Yi-Hsiu Chung ,&nbsp;Shih-Ting Hsu ,&nbsp;Jia-Min Mo ,&nbsp;Chun-Yi Wu ,&nbsp;Shin-Lei Peng","doi":"10.1016/j.nucmedbio.2024.108878","DOIUrl":"10.1016/j.nucmedbio.2024.108878","url":null,"abstract":"<div><h3>Objective</h3><p>Diabetic patients often experience chronic inflammation and fibrosis in their cardiac tissues, highlighting the pressing need for the development of sensitive diagnostic methods for longitudinal assessment of diabetic cardiomyopathy. This study aims to evaluate the significance of an inflammatory marker known as translocator protein (TSPO) in a positron emission tomography (PET) protocol for longitudinally monitoring cardiac dysfunction in a diabetic animal model. Additionally, we compared the commonly used radiotracer, ¹⁸F-fluoro-2-deoxy-<span>d</span>-glucose (¹⁸F-FDG).</p></div><div><h3>Methods</h3><p>Fourteen 7-week-old female Sprague-Dawley rats were used in this study. Longitudinal PET experiments were conducted using ¹⁸F-<em>N</em>-2-(2-fluoroethoxy)benzyl)-<em>N</em>-(4-phenoxypyridin-3-yl)acetamide (¹⁸F-FEPPA) (<em>n</em> = 3), the TSPO radiotracer, and ¹⁸F-FDG (n = 3), both before and after the onset of diabetes. Histological and immunohistochemical staining assays were also conducted in both the control (<em>n</em> = 4) and diabetes (n = 4) groups.</p></div><div><h3>Results</h3><p>Results indicated a significant increase in cardiac tissue uptake of ¹⁸F-FEPPA after the onset of diabetes (<em>P</em> &lt; 0.05), aligning with elevated TSPO levels observed in diabetic animals according to histological data. Conversely, the uptake of ¹⁸F-FDG in cardiac tissue significantly decreased after the onset of diabetes (P &lt; 0.05).</p></div><div><h3>Conclusion</h3><p>These findings suggest that ¹⁸F-FEPPA can function as a sensitive probe for detecting chronic inflammation and fibrosis in the cardiac tissues of diabetic animals.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"128 ","pages":"Article 108878"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000040/pdfft?md5=dc8dde21cd5f9959b65d3c8fb5d5d437&pid=1-s2.0-S0969805124000040-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139581731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of targeting αVβ3 in breast cancers using RGD peptide-based agents","authors":"Anders Josefsson ,&nbsp;Angel G. Cortez ,&nbsp;Jing Yu ,&nbsp;Sunipa Majumdar ,&nbsp;Abhinav Bhise ,&nbsp;Robert F. Hobbs ,&nbsp;Jessie R. Nedrow","doi":"10.1016/j.nucmedbio.2024.108880","DOIUrl":"10.1016/j.nucmedbio.2024.108880","url":null,"abstract":"<div><p>Patients with HER2-positive and triple negative breast cancer (TNBC) are associated with increased risk to develop metastatic disease including reoccurring disease that is resistant to standard and targeted therapies. The α_Vβ₃ has been implicated in BC including metastatic disease. The aims of this study were to investigate the potential of α_Vβ₃-targeted peptides to deliver radioactive payloads to BC tumors expressing α_Vβ₃ on the tumor cells or limited to the tumors' neovascular. Additionally, we aimed to assess the pharmacokinetic profile of the targeted α-particle therapy (TAT) agent [²²⁵Ac]Ac-DOTA-cRGDfK dimer peptide and the <em>in vivo</em> generated decay daughters. The expression of α_Vβ₃ in a HER2-positive and a TNBC cell line were evaluated using western blot analysis. The pharmacokinetics of [¹¹¹In]In-DOTA-cRGDfK dimer, a surrogate for the TAT-agent, was evaluated in subcutaneous mouse tumor models. The pharmacokinetic of the TAT-agent [²²⁵Ac]Ac-DOTA-cRGDfK dimer and its decay daughters were evaluated in healthy mice. Selective uptake of [¹¹¹In]In-DOTA-cRGDfK dimer was shown in subcutaneous tumor models using α_Vβ₃-positive tumor cells as well as α_Vβ₃-negative tumor cells where the expression is limited to the neovasculature. Pharmacokinetic studies demonstrated rapid accumulation in the tumors with clearance from non-target organs. Dosimetric analysis of [²²⁵Ac]Ac-DOTA-cRGDfK dimer showed the highest radiation absorbed dose to the kidneys, which included the contributions from the free <em>in vivo</em> generated decay daughters. This study shows the potential of delivering radioactive payloads to BC tumors that have α_Vβ₃ expression on the tumor cells as well as limited expression to the neovascular of the tumor. Furthermore, this work determines the radiation absorbed doses to normal organs/tissues and identified key organs that act as suppliers and receivers of the actinium-225 free <em>in vivo</em> generated α-particle-emitting decay daughters.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"128 ","pages":"Article 108880"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000064/pdfft?md5=69f8c9b3364d71e09beee8b1277b1dca&pid=1-s2.0-S0969805124000064-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information","authors":"","doi":"10.1016/S0969-8051(24)00013-1","DOIUrl":"https://doi.org/10.1016/S0969-8051(24)00013-1","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"128 ","pages":"Article 108887"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000131/pdfft?md5=edb2ec17d99abcff7f5435b79f5ca6e4&pid=1-s2.0-S0969805124000131-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139936796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}