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Introduction of a fatty acid chain modification to prolong circulatory half-life of a radioligand towards glucose-dependent insulinotropic polypeptide receptor 引入脂肪酸链修饰,延长葡萄糖依赖性促胰岛素多肽受体放射性配体的循环半衰期
IF 3.1 4区 医学
Nuclear medicine and biology Pub Date : 2024-01-01 DOI: 10.1016/j.nucmedbio.2024.108876
Amina Khalil , Sona Hakhverdyan , Pierre Cheung , Martin Bossart , Michael Wagner , Olof Eriksson , Irina Velikyan
{"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 , Sona Hakhverdyan , Pierre Cheung , Martin Bossart , Michael Wagner , Olof Eriksson , Irina Velikyan","doi":"10.1016/j.nucmedbio.2024.108876","DOIUrl":"10.1016/j.nucmedbio.2024.108876","url":null,"abstract":"<div><h3>Background</h3><p>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 <em>in vivo</em> 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 <em>in vivo</em> PET imaging and quantification of GIPR occupancy by novel drugs of interest.</p></div><div><h3>Method</h3><p>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 <em>via</em> 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 <sup>68</sup>Ga radiolabeling. The resulting PET probe, [<sup>68</sup>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. <em>Ex vivo</em> and <em>in vivo</em> organ distribution of [<sup>68</sup>Ga]Ga-DOTA-GIP1234 was studied in rats and a pig in comparison to [<sup>68</sup>Ga]Ga-DOTA-C803-GIP. Binding of [<sup>68</sup>Ga]Ga-DOTA-GIP1234 to albumin was assessed <em>in situ</em> using polyacrylamide gel electrophoresis (PAGE). The stability was tested in formulation buffer and rat blood plasma.</p></div><div><h3>Results</h3><p>[<sup>68</sup>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. [<sup>68</sup>Ga]Ga-DOTA-GIP1234 was stable and maintained affinity to huGIPR HEK293 cells (dissociation constant (K<sub>d</sub>) = 40 ± 12.5 nM). The binding of [<sup>68</sup>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 [<sup>68</sup>Ga]Ga-DOTA-GIP1234 binding by close to 90 %. [<sup>68</sup>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 [<sup>68</sup>Ga]Ga-DOTA-C803-GIP. [<sup>68</sup>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}
引用次数: 0
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 F-537-Tetrazine 在脑部预靶向成像模型中的评估。与 N-(3-[18F]氟-5-(1,2,4,5-四嗪-3-基)苄基)丙-1-胺的比较
IF 3.1 4区 医学
Nuclear medicine and biology Pub Date : 2024-01-01 DOI: 10.1016/j.nucmedbio.2024.108877
Vladimir Shalgunov , Sara Lopes van den Broek , Ida Vang Andersen , Nakul R. Raval , Gabriela Schäfer , Matthias Barz , Matthias M. Herth , Umberto M. Battisti
{"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-[<sup>18</sup>F]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-[<sup>18</sup>F] 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}
引用次数: 0
64Cu production via the 68Zn(p,nα)64Cu nuclear reaction: An untapped, cost-effective and high energy production route 通过 68Zn(p,nα)64Cu 核反应生产 64Cu:一条尚未开发的、具有成本效益的高能生产路线
IF 3.1 4区 医学
Nuclear medicine and biology Pub Date : 2024-01-01 DOI: 10.1016/j.nucmedbio.2024.108875
Bryce J.B. Nelson , Samantha Leier , John Wilson , Melinda Wuest , Jonathan Doupe , Jan D. Andersson , Frank Wuest
{"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}
引用次数: 0
Imaging diabetic cardiomyopathy in a type 1 diabetic rat model using 18F-FEPPA PET 利用 18F-FEPPA PET 对 1 型糖尿病大鼠模型中的糖尿病心肌病进行成像
IF 3.1 4区 医学
Nuclear medicine and biology Pub Date : 2024-01-01 DOI: 10.1016/j.nucmedbio.2024.108878
Hsin-Hua Hsieh , Pei-An Chu , Yu-Hsin Lin , Yu-Chieh Jill Kao , Yi-Hsiu Chung , Shih-Ting Hsu , Jia-Min Mo , Chun-Yi Wu , Shin-Lei Peng
{"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, <sup>18</sup>F-fluoro-2-deoxy-<span>d</span>-glucose (<sup>18</sup>F-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 <sup>18</sup>F-<em>N</em>-2-(2-fluoroethoxy)benzyl)-<em>N</em>-(4-phenoxypyridin-3-yl)acetamide (<sup>18</sup>F-FEPPA) (<em>n</em> = 3), the TSPO radiotracer, and <sup>18</sup>F-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 <sup>18</sup>F-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 <sup>18</sup>F-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 <sup>18</sup>F-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}
引用次数: 0
Evaluation of targeting αVβ3 in breast cancers using RGD peptide-based agents 使用基于 RGD 肽的制剂靶向乳腺癌中的αVβ3 的评估。
IF 3.1 4区 医学
Nuclear medicine and biology Pub Date : 2024-01-01 DOI: 10.1016/j.nucmedbio.2024.108880
Anders Josefsson , Angel G. Cortez , Jing Yu , Sunipa Majumdar , Abhinav Bhise , Robert F. Hobbs , Jessie R. Nedrow
{"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<sub>V</sub>β<sub>3</sub> has been implicated in BC including metastatic disease. The aims of this study were to investigate the potential of α<sub>V</sub>β<sub>3</sub>-targeted peptides to deliver radioactive payloads to BC tumors expressing α<sub>V</sub>β<sub>3</sub> 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 [<sup>225</sup>Ac]Ac-DOTA-cRGDfK dimer peptide and the <em>in vivo</em> generated decay daughters. The expression of α<sub>V</sub>β<sub>3</sub> in a HER2-positive and a TNBC cell line were evaluated using western blot analysis. The pharmacokinetics of [<sup>111</sup>In]In-DOTA-cRGDfK dimer, a surrogate for the TAT-agent, was evaluated in subcutaneous mouse tumor models. The pharmacokinetic of the TAT-agent [<sup>225</sup>Ac]Ac-DOTA-cRGDfK dimer and its decay daughters were evaluated in healthy mice. Selective uptake of [<sup>111</sup>In]In-DOTA-cRGDfK dimer was shown in subcutaneous tumor models using α<sub>V</sub>β<sub>3</sub>-positive tumor cells as well as α<sub>V</sub>β<sub>3</sub>-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 [<sup>225</sup>Ac]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<sub>V</sub>β<sub>3</sub> 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}
引用次数: 0
Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information 封底外页 - 双栏图文摘要 TOC/TOC/封面图像图例(如适用)、条形码、摘要和索引信息
IF 3.1 4区 医学
Nuclear medicine and biology Pub Date : 2024-01-01 DOI: 10.1016/S0969-8051(24)00013-1
{"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}
引用次数: 0
Fully automated dual-run manufacturing of [11C]PIB on FASTlab 在 FASTlab 上实现 [11C]PIB 的全自动双运行制造
IF 3.1 4区 医学
Nuclear medicine and biology Pub Date : 2023-12-25 DOI: 10.1016/j.nucmedbio.2023.108873
Manoj Nair , Yiu-Yin Cheung , Fei Liu , Mary Ellen Koran , Adam J. Rosenberg
{"title":"Fully automated dual-run manufacturing of [11C]PIB on FASTlab","authors":"Manoj Nair ,&nbsp;Yiu-Yin Cheung ,&nbsp;Fei Liu ,&nbsp;Mary Ellen Koran ,&nbsp;Adam J. Rosenberg","doi":"10.1016/j.nucmedbio.2023.108873","DOIUrl":"https://doi.org/10.1016/j.nucmedbio.2023.108873","url":null,"abstract":"<div><p>This report describes an updated, fully automated method for the production of [<sup>11</sup>C]PIB on a cassette-based automated synthesis module. The method allows for two separate productions of [<sup>11</sup>C]PIB, both of which meet all specification for use in clinical studies. The GE FASTlab developer system was used to create the cassette design as well as the controlling tracer package. The method takes 16 min from the delivery of [<sup>11</sup>C]MeOTf to the FASTlab, or 35 min from the End of Bombardment; and reliably produces 3547 ± 586 MBq of [<sup>11</sup>C]PIB in high radiochemical purity (&gt; 98 %). This methodology increases the production capacity of radiopharmaceutical facilities for [<sup>11</sup>C]PIB, and can easily produce 4 batches in a single day with limited infrastructure footprint.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"128 ","pages":"Article 108873"},"PeriodicalIF":3.1,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805123006017/pdfft?md5=3e75b6d224bfd7e1a19926b866ef9a2b&pid=1-s2.0-S0969805123006017-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139050153","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}
引用次数: 0
Chelation chemistry of manganese-52 for PET imaging applications 用于 PET 成像应用的锰-52 螯合化学
IF 3.1 4区 医学
Nuclear medicine and biology Pub Date : 2023-12-23 DOI: 10.1016/j.nucmedbio.2023.108874
James M. Omweri , Volkan Tekin , Shefali Saini , Hailey A. Houson , Samith B. Jayawardana , Daniel A. Decato , Gayan B. Wijeratne , Suzanne E. Lapi
{"title":"Chelation chemistry of manganese-52 for PET imaging applications","authors":"James M. Omweri ,&nbsp;Volkan Tekin ,&nbsp;Shefali Saini ,&nbsp;Hailey A. Houson ,&nbsp;Samith B. Jayawardana ,&nbsp;Daniel A. Decato ,&nbsp;Gayan B. Wijeratne ,&nbsp;Suzanne E. Lapi","doi":"10.1016/j.nucmedbio.2023.108874","DOIUrl":"10.1016/j.nucmedbio.2023.108874","url":null,"abstract":"<div><h3>Introduction</h3><p>Due to its decay and chemical properties, interest in manganese-52 has increased for development of long-lived PET radiopharmaceuticals. Its long half-life of 5.6 days, low average positron energy (242 keV), and sufficient positron decay branching ratio make it suitable for radiolabeling macromolecules for investigating slow biological processes. This work aims to establish suitable chelators for manganese-52 that can be radiolabeled at mild conditions through the evaluation of commercially available chelators.</p></div><div><h3>Methods</h3><p>Manganese-52 was produced through the nuclear reaction <sup>Nat</sup>Cr(p,n)<sup>52</sup>Mn by irradiation of natural chromium targets on a TR24 cyclotron followed by purification through ion exchange chromatography. The radiolabeling efficiencies of chelators: DOTA, DiAmsar, TETA, DO3A, NOTA, 4′-Formylbenzo-15-crown-5, Oxo-DO3A, and DFO, were assessed by investigating the impact of pH, buffer type, and temperature. <em>In vitro</em> stability of [<sup>52</sup>Mn]Mn(DO3A)<sup>−</sup>, [<sup>52</sup>Mn]Mn(Oxo-DO3A)<sup>−</sup>, and [<sup>52</sup>Mn]Mn(DOTA)<sup>2−</sup> were evaluated in mouse serum. The radiocomplexes were also evaluated <em>in vivo</em> in mice. Crystals of [Mn(Oxo-DO3A)]<sup>−</sup> were synthesized by reacting Oxo-DO3A with MnCl<sub>2</sub> and characterized by single crystal X-ray diffraction.</p></div><div><h3>Results</h3><p>Yields of 185 ± 19 MBq (5.0 ± 0.5 mCi) (n = 4) of manganese-52 were produced at the end of a 4 h, 15 μA, bombardment with 12.5 MeV protons. NOTA, DO3A, DOTA, and Oxo-DO3A chelators were readily radiolabeled with &gt;96 % radiochemical purity at all conditions. Manganese radiocomplexes of Oxo-DO3A, DOTA, and DO3A remained stable <em>in vitro</em> up to 5 days and exhibited different biodistribution profiles compared to [<sup>52</sup>Mn]MnCl<sub>2</sub>. The solid-state structure of Mn-Oxo-DO3A complex was determined by single-crystal X-ray diffraction.</p></div><div><h3>Conclusions</h3><p>DO3A and Oxo-DO3A are suitable chelators for manganese-52 which are readily radiolabeled at mild conditions with high molar activity, and demonstrate both <em>in vitro</em> and <em>in vivo</em> stability.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"128 ","pages":"Article 108874"},"PeriodicalIF":3.1,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805123006029/pdfft?md5=03b22d19bd51af10dd7051d5419ab246&pid=1-s2.0-S0969805123006029-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139031358","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}
引用次数: 0
Development of 18F-Labelled CXCR4-Targeted Peptide Radiopharmaceuticals Through Strain-Promoted Click Chemistry 利用菌株促进的点击化学方法开发18f标记的cxcr4靶向肽放射性药物
IF 3.1 4区 医学
Nuclear medicine and biology Pub Date : 2023-11-01 DOI: 10.1016/j.nucmedbio.2023.108406
Julia Mason, Len Luyt
{"title":"Development of 18F-Labelled CXCR4-Targeted Peptide Radiopharmaceuticals Through Strain-Promoted Click Chemistry","authors":"Julia Mason,&nbsp;Len Luyt","doi":"10.1016/j.nucmedbio.2023.108406","DOIUrl":"https://doi.org/10.1016/j.nucmedbio.2023.108406","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"126 ","pages":"Article 108406"},"PeriodicalIF":3.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500794","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}
引用次数: 0
StarPEG Nanocarriers for PSMA Targeted Radioligand Imaging and Therapy 用于PSMA靶向放射配体成像和治疗的StarPEG纳米载体
IF 3.1 4区 医学
Nuclear medicine and biology Pub Date : 2023-11-01 DOI: 10.1016/j.nucmedbio.2023.108400
Anil Bidkar, Niranjan Meher, Gary Ashley, Anju Wadhwa, Kondapa Bobba, Becka Shuere, David Wilson, Youngho Seo, Daniel Santi, Henry VanBrocklin, Robert Flavell
{"title":"StarPEG Nanocarriers for PSMA Targeted Radioligand Imaging and Therapy","authors":"Anil Bidkar,&nbsp;Niranjan Meher,&nbsp;Gary Ashley,&nbsp;Anju Wadhwa,&nbsp;Kondapa Bobba,&nbsp;Becka Shuere,&nbsp;David Wilson,&nbsp;Youngho Seo,&nbsp;Daniel Santi,&nbsp;Henry VanBrocklin,&nbsp;Robert Flavell","doi":"10.1016/j.nucmedbio.2023.108400","DOIUrl":"https://doi.org/10.1016/j.nucmedbio.2023.108400","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"126 ","pages":"Article 108400"},"PeriodicalIF":3.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500876","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}
引用次数: 0
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