Nuclear medicine and biology最新文献

{"title":"Initial insights into the interaction of antibodies radiolabeled with Lutetium-177 and Actinium-225 with tumor microenvironment in experimental human and canine osteosarcoma","authors":"Sabeena Giri ,&nbsp;Kevin J.H. Allen ,&nbsp;Chandra Bose Prabaharan ,&nbsp;Jonathan Bonet Ramirez ,&nbsp;Luciano Fiore ,&nbsp;Maruti Uppalapati ,&nbsp;Ekaterina Dadachova","doi":"10.1016/j.nucmedbio.2024.108917","DOIUrl":"https://doi.org/10.1016/j.nucmedbio.2024.108917","url":null,"abstract":"<div><h3>Background</h3><p>Osteosarcoma (OS) is a prevalent primary bone cancer affecting both humans and canines. This study describes initial insights into the interaction of the human monoclonal antibody IF3 to an insulin-like growth factor 2 receptor (IGF2R) radiolabeled with either alpha-emitting Actinium-225 (²²⁵Ac) or beta-emitting Lutetium-177 (¹⁷⁷Lu) radionuclides with the OS cells and tumor microenvironment (TME) in experimental human and canine OS.</p></div><div><h3>Basic procedures</h3><p>SCID mice bearing canine Gracie or human OS-33 OS tumors were treated with ¹⁷⁷Lu- or ²²⁵Ac-labeled IF3 antibody, sacrificed at 24, 72 or 168 h post-treatment and their tumors were analyzed by immunohistochemistry (IHC) for the presence of OS cells, various elements of TME as well as for the double DNA strand breaks with γH2AX and caspase 3 assays.</p></div><div><h3>Main findings</h3><p>IHC revealed a reduction in IGF2R-positive OS cells and OS stem cell populations post therapy with ²²⁵Ac- and ¹⁷⁷Lu-labeled IF3 antibody. Notably, radiolabeled IF3 antibody effectively diminished pro-tumorigenic M2 macrophages, highlighting its therapeutic promise. The study also unveiled varied responses of natural killer (NK) cells and M1 macrophages, shedding light on the intricate TME interplay. Time-dependent increase in γ-H2AX staining in canine Gracie and human OS-33 tumors treated with [¹⁷⁷Lu]Lu-IF3 and [²²⁵Ac]Ac-IF3 was observed at 24 and 72 h post-RIT.</p></div><div><h3>Principal conclusions</h3><p>These findings suggest that radiolabeled antibodies offer a hopeful avenue for personalized OS treatment, emphasizing the importance of understanding their impact on the TME and potential synergies with immunotherapy.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"134 ","pages":"Article 108917"},"PeriodicalIF":3.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S096980512400043X/pdfft?md5=168cb5154a03550d16ee0a9022304c41&pid=1-s2.0-S096980512400043X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140879416","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":"A third generation PSMA-targeted agent [211At]YF2: Synthesis and in vivo evaluation","authors":"Yutian Feng ,&nbsp;Rebecca L. Meshaw ,&nbsp;Sean W. Finch ,&nbsp;Yongxiang Zheng ,&nbsp;Il Minn ,&nbsp;Ganesan Vaidyanathan ,&nbsp;Martin G. Pomper ,&nbsp;Michael R. Zalutsky","doi":"10.1016/j.nucmedbio.2024.108916","DOIUrl":"https://doi.org/10.1016/j.nucmedbio.2024.108916","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;Targeted α-particle therapy agents have shown promising responses in patients who have developed resistance to β&lt;sup&gt;−&lt;/sup&gt;-particle emitting radionuclides, albeit off-target toxicity remains a concern. Astatine-211 emits only one α-particle per decay and may alleviate the toxicity from α-emitting daughter radionuclides. Previously, we developed the low-molecular-weight PSMA-targeted agent [&lt;sup&gt;211&lt;/sup&gt;At]L3-Lu that showed suitable therapeutic efficacy and was well tolerated in mice. Although [&lt;sup&gt;211&lt;/sup&gt;At]L3-Lu had good characteristics, we now have evaluated a closely related analogue, [&lt;sup&gt;211&lt;/sup&gt;At]YF2, to determine the better molecule for clinical translation.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;The tin precursors and unlabeled iodo standards for [&lt;sup&gt;211&lt;/sup&gt;At]YF2 and [&lt;sup&gt;211&lt;/sup&gt;At]L3-Lu each were synthesized and a new one-step labeling method was developed to produce [&lt;sup&gt;211&lt;/sup&gt;At]YF2 and [&lt;sup&gt;211&lt;/sup&gt;At]L3-Lu from the respective tin precursor. RCY and RCP were determined using RP-HPLC. Cell uptake, internalization and in vitro cell-killing (MTT) assays were performed on PSMA&lt;sup&gt;+&lt;/sup&gt; PC-3 PIP cells in parallel experiments to compare [&lt;sup&gt;211&lt;/sup&gt;At]YF2 and [&lt;sup&gt;211&lt;/sup&gt;At]L3-Lu directly. A paired-label biodistribution study was performed in athymic mice with subcutaneous PSMA-positive PC-3 PIP xenografts as a head-to-head comparison of [&lt;sup&gt;131&lt;/sup&gt;I]YF2 and [&lt;sup&gt;125&lt;/sup&gt;I]L3-Lu. The tissue distribution of [&lt;sup&gt;211&lt;/sup&gt;At]YF2 and [&lt;sup&gt;211&lt;/sup&gt;At]L3-Lu were determined individually in the same animal model.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The syntheses of tin precursors and unlabeled iodo standards were accomplished in reasonable yields. A streamlined and scalable radiolabeling method (1 h total synthesis time) was developed for the radiosynthesis of both [&lt;sup&gt;211&lt;/sup&gt;At]YF2 and [&lt;sup&gt;211&lt;/sup&gt;At]L3-Lu with 86 ± 7 % (&lt;em&gt;n&lt;/em&gt; = 10) and 87 ± 5 % (&lt;em&gt;n&lt;/em&gt; = 7) RCY, respectively, and &gt; 95 % RCP for both. The maximum activity of [&lt;sup&gt;211&lt;/sup&gt;At]YF2 produced to date was 666 MBq. An alternative method that did not involve HPLC purification was developed that provided similar RCY and RCP. Significantly higher cell uptake, internalization and cytotoxicity was seen for [&lt;sup&gt;211&lt;/sup&gt;At]YF2 compared with [&lt;sup&gt;211&lt;/sup&gt;At]L3-Lu. Significantly higher uptake and longer retention in tumor was seen for [&lt;sup&gt;131&lt;/sup&gt;I]YF2 than for co-administered [&lt;sup&gt;125&lt;/sup&gt;I]L3-Lu, while considerably higher renal uptake was seen for [&lt;sup&gt;131&lt;/sup&gt;I]YF2. The biodistribution of [&lt;sup&gt;211&lt;/sup&gt;At]YF2 was consistent with that of [&lt;sup&gt;131&lt;/sup&gt;I]YF2.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;[&lt;sup&gt;211&lt;/sup&gt;At]YF2 exhibited higher cellular uptake, internalization and cytotoxicity than [&lt;sup&gt;211&lt;/sup&gt;At]L3-Lu on PSMA-positive PC3 PIP cells. Likewise, higher uptake and longer retention in tumor was seen for [&lt;sup&gt;211&lt;/sup&gt;At]YF2. Experiments to evaluate the dosimetry and therapeutic efficacy of [&lt;sup&gt;","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"134 ","pages":"Article 108916"},"PeriodicalIF":3.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825684","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":"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)00050-7","DOIUrl":"https://doi.org/10.1016/S0969-8051(24)00050-7","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"132 ","pages":"Article 108924"},"PeriodicalIF":3.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000507/pdfft?md5=359ac03ddcae9fdce06b779383335b91&pid=1-s2.0-S0969805124000507-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097512","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":"Application of copper (I) selective ligands for PET imaging of reactive oxygen species through metabolic trapping","authors":"Tetsuro Tada ,&nbsp;Yuki Mizuno ,&nbsp;Yuki Shibata ,&nbsp;Hironobu Yasui ,&nbsp;Yuji Kuge","doi":"10.1016/j.nucmedbio.2024.108914","DOIUrl":"https://doi.org/10.1016/j.nucmedbio.2024.108914","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;Reactive oxygen species (ROS) are attractive targets for clinical PET imaging. In this study, we hypothesized that PET imaging of ROS would be possible by using chelating ligands (L) that form stable complexes with copper (I) but not with copper (II), based on metabolic trapping. Namely, when [&lt;sup&gt;64&lt;/sup&gt;Cu][Cu&lt;sup&gt;I&lt;/sup&gt;(L)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;+&lt;/sup&gt; is oxidized by ROS, the oxidized complex will release [&lt;sup&gt;64&lt;/sup&gt;Cu]Cu&lt;sup&gt;2+&lt;/sup&gt;. Then, the released [&lt;sup&gt;64&lt;/sup&gt;Cu]Cu&lt;sup&gt;2+&lt;/sup&gt; will be trapped inside the cell, resulting in PET signal depending on the redox potential of ROS. To examine the potential of this novel molecular design for ROS imaging, we synthesized copper (I) complexes with bicinchoninic acid (BCA) disodium salt and bathocuproinedisulfonic acid (BCS) disodium salt and evaluated their reactivity with several kinds of ROS. In addition, the cellular uptake of [&lt;sup&gt;64&lt;/sup&gt;Cu][Cu&lt;sup&gt;I&lt;/sup&gt;(BCS)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;3−&lt;/sup&gt; and the stability of [&lt;sup&gt;64&lt;/sup&gt;Cu][Cu&lt;sup&gt;I&lt;/sup&gt;(BCS)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;3−&lt;/sup&gt; in a biological condition were also evaluated.&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]Cu&lt;sup&gt;2+&lt;/sup&gt; was reduced to [&lt;sup&gt;64&lt;/sup&gt;Cu]Cu&lt;sup&gt;+&lt;/sup&gt; by ascorbic acid and coordinated with BCA and BCS in the acetate buffer to synthesize [&lt;sup&gt;64&lt;/sup&gt;Cu][Cu&lt;sup&gt;I&lt;/sup&gt;(BCA)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;3−&lt;/sup&gt; and [&lt;sup&gt;64&lt;/sup&gt;Cu][Cu&lt;sup&gt;I&lt;/sup&gt;(BCS)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;3−&lt;/sup&gt;. The radiochemical yields were determined by thin-layer chromatography (TLC). After [&lt;sup&gt;64&lt;/sup&gt;Cu][Cu&lt;sup&gt;I&lt;/sup&gt;(BCS)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;3−&lt;/sup&gt; was incubated with hydroxyl radical, lipid peroxide, superoxide, and hydrogen peroxide, the percentage of released [&lt;sup&gt;64&lt;/sup&gt;Cu]Cu&lt;sup&gt;2+&lt;/sup&gt; from the parent complex was evaluated by TLC. HT-1080 human fibrosarcoma cells were treated with 0.1 % Dimethyl sulfoxide (control), imidazole ketone erastin (IKE), or IKE + ferrostatin-1 (Fer-1). Then, the uptake of [&lt;sup&gt;64&lt;/sup&gt;Cu][Cu&lt;sup&gt;I&lt;/sup&gt;(BCS)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;3−&lt;/sup&gt; to HT-1080 cells in each group was evaluated as %Dose/mg protein. Lastly, [&lt;sup&gt;64&lt;/sup&gt;Cu][Cu&lt;sup&gt;I&lt;/sup&gt;(BCS)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;3−&lt;/sup&gt; was incubated in human plasma, and its intact ratio was determined by TLC.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The radiochemical yield of [&lt;sup&gt;64&lt;/sup&gt;Cu][Cu&lt;sup&gt;I&lt;/sup&gt;(BCS)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;3−&lt;/sup&gt; (86 ± 1 %) was higher than that of [&lt;sup&gt;64&lt;/sup&gt;Cu][Cu&lt;sup&gt;I&lt;/sup&gt;(BCA)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;3−&lt;/sup&gt; (44 ± 3 %). [&lt;sup&gt;64&lt;/sup&gt;Cu][Cu&lt;sup&gt;I&lt;/sup&gt;(BCA)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;3−&lt;/sup&gt; was unstable and partially decomposed on TLC. After [&lt;sup&gt;64&lt;/sup&gt;Cu][Cu&lt;sup&gt;I&lt;/sup&gt;(BCS)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;3−&lt;/sup&gt; was reacted with hydroxyl radical, lipid peroxide, and superoxide, 67 ± 2 %, 44 ± 13 %, and 22 ± 3 % of total radioactivity was detected as [&lt;sup&gt;64&lt;/sup&gt;Cu]Cu&lt;sup&gt;2+&lt;/sup&gt;, respectively. On the other hand, the reaction with hydrogen peroxide did not significantly increase the ratio of [&lt;sup&gt;64&lt;/sup&gt;Cu]Cu&lt;sup&gt;2+&lt;/sup&gt; (4 ± 1 %). These results s","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"134 ","pages":"Article 108914"},"PeriodicalIF":3.1,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905511","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":"Synthesis and evaluation of a 68Ga-labeled spermine derivative for tumor PET imaging","authors":"Kaixin Qin ,&nbsp;Dongmei Shi ,&nbsp;Yuzhou Zheng ,&nbsp;Wenhao Hu ,&nbsp;Xiameng Kang ,&nbsp;Ping Wu ,&nbsp;Xinzhong Hao ,&nbsp;Haiyan Liu ,&nbsp;Jie Gao ,&nbsp;Jianguo Li ,&nbsp;Zhifang Wu ,&nbsp;Sijin Li ,&nbsp;Hongliang Wang","doi":"10.1016/j.nucmedbio.2024.108915","DOIUrl":"https://doi.org/10.1016/j.nucmedbio.2024.108915","url":null,"abstract":"<div><h3>Background</h3><p>The polyamine transporter system (PTS), which renders it a promising target for tumor therapy and imaging applications, facilitates the transmembrane transport of polyamines. We reported a novel derivative of spermine labeled with gallium-68 ([⁶⁸Ga]Ga-NOTA-Spermine) for the imaging of the PTS in mouse models of tumor.</p></div><div><h3>Results</h3><p>The radiochemical yield of [⁶⁸Ga]Ga-NOTA-Spermine was determined to be 64–69 %, demonstrating exceptional stability and radiochemical purity (&gt;98 %). Cellular uptake experiments revealed that A549 cells exhibited peak uptake of [⁶⁸Ga]Ga-NOTA-Spermine at 90 min (15.4 % ± 0.68 %). Biodistribution analysis demonstrated significant accumulation of [⁶⁸Ga]Ga-NOTA-Spermine in kidneys and liver, while exhibiting low uptake levels in muscle, brain, and bones. Furthermore, Micro-PET/CT scans conducted on A549 tumor-bearing mouse models indicated substantial uptake of [⁶⁸Ga]Ga-NOTA-Spermine, with maximum tumor/muscle (T/M) ratios reaching 3.71.</p></div><div><h3>Conclusion</h3><p>These results suggest that [⁶⁸Ga]Ga-NOTA-Spermine holds potential as a PET imaging agent for tumors with high levels of PTS.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"134 ","pages":"Article 108915"},"PeriodicalIF":3.1,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140893505","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":"PSMA-reactive NB7 single domain antibody fragment: A potential scaffold for developing prostate cancer theranostics","authors":"Truc T. Huynh ,&nbsp;Yutian Feng ,&nbsp;Rebecca Meshaw ,&nbsp;Xiao-Guang Zhao ,&nbsp;Lior Rosenfeld ,&nbsp;Ganesan Vaidyanathan ,&nbsp;Niv Papo ,&nbsp;Michael R. Zalutsky","doi":"10.1016/j.nucmedbio.2024.108913","DOIUrl":"10.1016/j.nucmedbio.2024.108913","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;Single domain antibody fragments (sdAbs) are an appealing scaffold for radiopharmaceutical development due to their small size (~15 kDa), high solubility, high stability, and excellent tumor penetration. Previously, we developed NB7 sdAb, which has very high affinity for an epitope on PSMA that is different from those targeted by small molecule PSMA inhibitors. Herein, we evaluated NB7 after radioiodination using [*I]SGMIB (1,3,4-isomer) and &lt;em&gt;iso&lt;/em&gt;-[*I]SGMIB (1,3,5-isomer), as well as their &lt;sup&gt;211&lt;/sup&gt;At-labeled analogues.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;[*I]SGMIB, &lt;em&gt;iso&lt;/em&gt;-[*I]SGMIB, [&lt;sup&gt;211&lt;/sup&gt;At]SAGMB, and &lt;em&gt;iso&lt;/em&gt;-[&lt;sup&gt;211&lt;/sup&gt;At]SAGMB conjugates of NB7 sdAb were synthesized and their binding affinity, cell uptake and internalization were assessed in PSMA&lt;sup&gt;+&lt;/sup&gt; PC3 PIP and PSMA&lt;sup&gt;−&lt;/sup&gt; PC3 flu cells. Biodistribution studies were performed in mice bearing PSMA&lt;sup&gt;+&lt;/sup&gt; PC3 PIP xenografts. First, a single-label experiment evaluated the tissue distribution of a NB7 bearing a His&lt;sub&gt;6&lt;/sub&gt;-tag (NB7H6) and labeled with &lt;em&gt;iso&lt;/em&gt;-[&lt;sup&gt;125&lt;/sup&gt;I]SGMIB. Three paired-label experiments then were performed to compare: a) NB7 labeled using [*I]SGMIB and &lt;em&gt;iso&lt;/em&gt;-[*I]SGMIB, b) &lt;sup&gt;131&lt;/sup&gt;I- vs &lt;sup&gt;211&lt;/sup&gt;At-labeled NB7 conjugates and c) [&lt;sup&gt;125&lt;/sup&gt;I]SGMIB-NB7H6 to the small molecule PSMA inhibitor [&lt;sup&gt;131&lt;/sup&gt;I]YF2.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;All NB7 radioconjugates bound specifically to PSMA with dissociation constants, K&lt;sub&gt;d&lt;/sub&gt;, in the low nM range (1.4–6.4 nM). An initial biodistribution study demonstrated good tumor uptake for &lt;em&gt;iso&lt;/em&gt;-[&lt;sup&gt;125&lt;/sup&gt;I]SGMIB-NB7H6 (7.2 ± 1.5 % ID/g at 1 h) and no deleterious effect of the His&lt;sub&gt;6&lt;/sub&gt;-tag on renal activity levels, which declined to 3.1 ± 1.1 % ID/g by 4 h. Paired-label biodistribution found no distinction between the two SGMIB isomer NB7 conjugates with the [&lt;sup&gt;131&lt;/sup&gt;I]SGMIB-NB7-to-&lt;em&gt;iso&lt;/em&gt;-[&lt;sup&gt;125&lt;/sup&gt;I]SGMIB-NB7 tumor uptake ratios not significantly different from unity: 1.06 ± 0.08 at 1 h, 1.04 ± 0.12 at 4 h, and 1.07 ± 0.09 at 24 h. Both isomer conjugates cleared rapidly from normal tissues and exhibited very low uptake in thyroid, lacrimal and salivary glands. Paired-label biodistribution of [&lt;sup&gt;131&lt;/sup&gt;I]SGMIB-NB7H6 and [&lt;sup&gt;211&lt;/sup&gt;At]SAGMB-NB7H6 demonstrated similar tumor uptake and kidney clearance for the two radioconjugates. However, levels of &lt;sup&gt;211&lt;/sup&gt;At in thyroid, stomach, salivary and lacrimal glands were significantly higher (&lt;em&gt;P&lt;/em&gt; &lt; 0.05) that those for &lt;sup&gt;131&lt;/sup&gt;I suggesting greater dehalogenation for [&lt;sup&gt;211&lt;/sup&gt;At]SAGMB-NB7H6. Finally, co-administration of [&lt;sup&gt;125&lt;/sup&gt;I]SGMIB-NB7H6 and [&lt;sup&gt;131&lt;/sup&gt;I]YF2 demonstrated good tumor uptake for both with considerably more rapid renal clearance for the NB7 radioconjugate.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;NB7 radioconjugates exhibited good accumulation in PSMA-positive xenografts with rapi","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"134 ","pages":"Article 108913"},"PeriodicalIF":3.1,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140795957","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":"Chemokine receptor PET imaging: Bridging molecular insights with clinical applications","authors":"Chanelle Hunter ,&nbsp;Benjamin Larimer","doi":"10.1016/j.nucmedbio.2024.108912","DOIUrl":"10.1016/j.nucmedbio.2024.108912","url":null,"abstract":"<div><p>Chemokine receptors are important components of cellular signaling and play a critical role in directing leukocytes during inflammatory reactions. Their importance extends to numerous pathological processes, including tumor differentiation, angiogenesis, metastasis, and associations with multiple inflammatory disorders. The necessity to monitor the in vivo interactions of cellular chemokine receptors has been driven the recent development of novel positron emission tomography (PET) imaging agents. This imaging modality provides non-invasive localization and quantitation of these receptors that cannot be provided through blood or tissue-based assays. Herein, we provide a review of PET imaging of the chemokine receptors that have been imaged to date, namely CXCR3, CXCR4, CCR2, CCR5, and CMKLR1. The quantification of these receptors can aid in understanding various diseases, including cancer, atherosclerosis, idiopathic pulmonary fibrosis, and acute respiratory distress syndrome. The development of specific radiotracers targeting these receptors will be discussed, including promising results for disease diagnosis and management. However, challenges persist in fully translating these imaging advancements into practical therapeutic applications. Given the success of CXCR4 PET imaging to date, future research should focus on clinical translation of these approaches to understand their role in the management of a wide variety of diseases.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"134 ","pages":"Article 108912"},"PeriodicalIF":3.1,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140779046","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":"Reduction of the hepatic radioactivity levels of [111In]In-DOTA–labeled antibodies via cleavage of a linkage metabolized in lysosomes","authors":"Hiroyuki Suzuki,&nbsp;Masato Matsukawa,&nbsp;Rikako Madokoro,&nbsp;Yui Terasaka,&nbsp;Kento Kannaka,&nbsp;Tomoya Uehara","doi":"10.1016/j.nucmedbio.2024.108910","DOIUrl":"https://doi.org/10.1016/j.nucmedbio.2024.108910","url":null,"abstract":"<div><h3>Introduction</h3><p>Radiolabeled antibodies are promising tools for cancer diagnosis using nuclear medicine. A DOTA-chelating system is useful for preparing immuno-positron emission tomography and immuno-single-photon emission computed tomography probes with various radiometals. Radiolabeled antibodies are generally metabolized in the reticuloendothelial system, producing radiometabolites after proteolysis in hepatic lysosomes. Because of the bulkiness and extremely high hydrophilicity of DOTA, radiometabolites containing a radiometal–DOTA complex typically exhibit high and persistent localization in hepatic lysosomes. Radioactivity in the liver impairs the accurate diagnosis of cancer surrounding the liver and liver metastasis, and a high tumor/liver ratio is desirable. In this study, we reduced the hepatic radioactivity of radiometal-labeled antibodies containing a DOTA-chelating system. A cleavable linkage was inserted to liberate the radiometabolite, which exhibited a short residence time in hepatocytes.</p></div><div><h3>Methods</h3><p>Using indium-111 (¹¹¹In)-labeled antibodies, we prepared ¹¹¹In-labeled galactosyl-neoglycoalbumins (NGAs) because they are useful for evaluating the residence time of radiometabolites in the liver. An ¹¹¹In-labeled NGA with a cleavable linkage ([¹¹¹In]In-DO3A<em>i</em>Bu-Bn-FGK-NGA) was administered to normal mice, and biodistribution studies and metabolic analyses of urinary and fecal samples were performed with comparison to an ¹¹¹In-labeled NGA prepared by a conventional method ([¹¹¹In]In-DOTA-Bn-SCN-NGA). Then, ¹¹¹In-labeled antibodies ([¹¹¹In]In-DO3A<em>i</em>Bu-Bn-FGK-IgG and [¹¹¹In]In-DOTA-Bn-SCN-IgG) were prepared using a procedure similar to that for ¹¹¹In-labeled NGAs. In vitro plasma stability and biodistribution were investigated for both ¹¹¹In-labeled antibodies in U87MG tumor-bearing mice.</p></div><div><h3>Results</h3><p>Through the liberation of radiometabolites including [¹¹¹In]In-DO3A<em>i</em>Bu-Bn-F, [¹¹¹In]In-DO3A<em>i</em>Bu-Bn-FGK-NGA was cleared more rapidly from the liver than [¹¹¹In]In-DOTA-Bn-SCN-NGA (4.07 ± 1.54%ID VS 71.68 ± 3.03%ID at 6 h postinjection). [¹¹¹In]In-DO3A<em>i</em>Bu-Bn-FGK-IgG exhibited lower tumor accumulation (8.83 ± 1.48%ID/g) but a significantly higher tumor/liver ratio (2.21 ± 0.53) than [¹¹¹In]In-DOTA-Bn-SCN-IgG (11.65 ± 2.17%ID/g in the tumor and a tumor/liver ratio of 0.85 ± 0.18) at 72 h after injection.</p></div><div><h3>Conclusion</h3><p>A molecular design that reduces the high and persistent hepatic radioactivity of radiolabeled antibodies by liberating radiometabolites with a short hepatic residence time in lysosomes would be applicable for radiometal-labeled antibodies using a DOTA-chelating system.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"132 ","pages":"Article 108910"},"PeriodicalIF":3.1,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000362/pdfft?md5=68d66421058c8d9a7626bcd028cba731&pid=1-s2.0-S0969805124000362-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140604481","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":"Synthesis and evaluation of novel trifunctional chelating agents for pretargeting approach using albumin binder to improve tumor accumulation","authors":"Shohei Tsuchihashi,&nbsp;Kazuma Nakashima,&nbsp;Hiroyuki Watanabe,&nbsp;Masahiro Ono","doi":"10.1016/j.nucmedbio.2024.108911","DOIUrl":"https://doi.org/10.1016/j.nucmedbio.2024.108911","url":null,"abstract":"<div><h3>Introduction</h3><p>The pretargeting approach consists of <em>in vivo</em> ligation between pre-injected antibodies and low-molecular-weight radiolabeled effectors. The advantage of the pretargeting approach is to improve a tumor-to-background ratio, but the disadvantage is to compromise tumor accumulation. In this study, we applied albumin binder (ALB) to the pretargeting approach to overcome low tumor accumulation.</p></div><div><h3>Methods</h3><p>We synthesized two novel trifunctional effectors containing an ALB moiety, a chelator, and a different tetrazine and two corresponding effectors without an ALB moiety. Albumin-binding assays and stability assays were performed using ¹¹¹In-labeled effectors. Measurements of reaction rate constant were conducted using ¹¹¹In-labeled effectors and anti-HER2 antibody trastuzumab modified by <em>trans-</em>cyclooctene, which drives the click reaction with tetrazine. Biodistribution studies using HER2-expressing tumor-bearing mice were performed with or without the pretargeting approach.</p></div><div><h3>Results</h3><p>In albumin-binding assays, ALB-containing effectors exhibited a marked binding to albumin. Two ALB-containing effectors showed the difference in the reactivity and the slight difference in the stability. In biodistribution studies without the pretargeting approach, two ALB-containing effectors showed different pharmacokinetics in blood retention. With the pretargeting approach, the tumor accumulation was improved by the introduction of ALB and the highest tumor accumulation was observed in using the ALB-containing effector with higher blood retention.</p></div><div><h3>Conclusion</h3><p>These results suggest that the application of ALB to the pretargeting approach is effective to improve tumor accumulation, and the structure of tetrazine influences the utility of ALB-containing effectors.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"132 ","pages":"Article 108911"},"PeriodicalIF":3.1,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140546005","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":"Development of 225Ac/213Bi generator based on α-ZrP-PAN composite for targeted alpha therapy","authors":"Lukáš Ondrák ,&nbsp;Kateřina Ondrák Fialová ,&nbsp;Michal Sakmár ,&nbsp;Martin Vlk ,&nbsp;Frank Bruchertseifer ,&nbsp;Alfred Morgenstern ,&nbsp;Ján Kozempel","doi":"10.1016/j.nucmedbio.2024.108909","DOIUrl":"10.1016/j.nucmedbio.2024.108909","url":null,"abstract":"<div><h3>Background</h3><p>Radioligand therapy using alpha emitters has gained more and more prominence in the last decade. Despite continued efforts to identify new appropriate radionuclides, the combination of ²²⁵Ac/²¹³Bi remains among the most promising. Bismuth-213 has been employed in clinical trials in combination with appropriate vectors to treat patients with various forms of cancer, such as leukaemia, bladder cancer, neuroendocrine tumours, melanomas, gliomas, or lymphomas. However, the half-life of ²¹³Bi (<em>T</em>_½ = 46 min) implies that its availability for clinical use is limited to hospitals possessing a ²²⁵Ac/²¹³Bi radionuclide generator, which is still predominantly scarce. We investigated a new Ac/Bi generator system based on using the composite sorbent α-ZrP-PAN (zirconium(IV) phosphate as active component and polyacrylonitrile as matrix). The developed ²²⁵Ac/²¹³Bi generator was subjected to long-term testing after its development. The elution profile was determined and the elution yield, the contamination of the eluate with the parent ²²⁵Ac and the contamination of the eluate with the column material were monitored over time.</p></div><div><h3>Results</h3><p>The high activity (75 MBq of parent ²²⁵Ac) generator with a length of 75 mm and a diameter of 4 mm containing the composite sorbent α-ZrP-PAN with a particle size of 0.8 to 1.0 mm as the stationary phase, eluted with a mixture of 10 mM DTPA in 5 mM nitric acid, provided ²¹³Bi with yields ranging from 77 % to 96 % in 2.8 mL of eluate, with parent ²²⁵Ac contamination in the order of 10⁻³ %, up to twenty days of use.</p></div><div><h3>Conclusion</h3><p>All the results of the monitored parameters indicate that the composite sorbent α-ZrP-PAN based separation system for the elution of ²¹³Bi is a very promising and functional solution.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"132 ","pages":"Article 108909"},"PeriodicalIF":3.1,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140400544","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}