Nuclear medicine and biology最新文献

{"title":"Actinium-225 photonuclear production in nuclear reactors using a mixed radium-226 and gadolinium-157 target","authors":"Artem V. Matyskin ,&nbsp;Susanna B. Angermeier ,&nbsp;Saleem S. Drera ,&nbsp;Michael C. Prible ,&nbsp;Jeffrey A. Geuther ,&nbsp;Michael D. Heibel","doi":"10.1016/j.nucmedbio.2024.108940","DOIUrl":"10.1016/j.nucmedbio.2024.108940","url":null,"abstract":"<div><h3>Background</h3><p>Actinium-225 is one of the most promising radionuclides for targeted alpha therapy. Its limited availability significantly restricts clinical trials and potential applications of ²²⁵Ac-based radiopharmaceuticals.</p></div><div><h3>Methods</h3><p>In this work, we examine the possibility of ²²⁵Ac production from the thermal neutron flux of a nuclear reactor. For this purpose, a target consisting of 1.4 mg of ²²⁶Ra(NO₃)₂ (T_1/2 = 1600 years) and 115.5 mg of 90 % enriched, stable ¹⁵⁷Gd₂O₃ was irradiated for 48 h in the Breazeale Nuclear Reactor with an average neutron flux of 1.7·10¹³ cm⁻²·s⁻¹. Gadolinium-157 has one of the highest thermal neutron capture cross sections of 0.25 Mb, and its neutron capture results in emission of high-energy, prompt γ-photons. Emitted γ-photons interact with ²²⁶Ra to produce ²²⁵Ra according to the ²²⁶Ra(γ, n)²²⁵Ra reaction. Gadolinium debulking and separation of undesirable, co-produced ²²⁷Ac from ²²⁵Ra was achieved in one step by using 60 g of branched DGA resin. After ²²⁵Ac ingrowth from ²²⁵Ra (T_1/2 = 14.8 d), ²²⁵Ac was extracted from the ²²⁶Ra and ²²⁵Ra fraction using 5 g of bDGA resin and then eluted using 5 mM HNO₃.</p></div><div><h3>Results</h3><p>Measured activity of ²²⁵Ac showed that 6(1) kBq or 0.16(3) μCi (1σ) of ²²⁵Ra was produced at the end of bombardment from 0.9 mg of ²²⁶Ra.</p></div><div><h3>Conclusion</h3><p>The developed ²²⁵Ac separation is a waste-free process which can be used to obtain pure ²²⁵Ac in a nuclear reactor.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"136 ","pages":"Article 108940"},"PeriodicalIF":3.6,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603993","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":"Transcatheter pseudo-vascular isolation for localization and concentration of a large molecule theranostic probe into a transgenic OncoPIG kidney tumor","authors":"Samuel L. Rice ,&nbsp;Fernando Gómez Muñoz ,&nbsp;Jamaal Benjamin ,&nbsp;Mhd Wisam Alnablsi ,&nbsp;Anil Pillai ,&nbsp;Joseph R. Osborne ,&nbsp;Regina Beets-Tan","doi":"10.1016/j.nucmedbio.2024.108939","DOIUrl":"https://doi.org/10.1016/j.nucmedbio.2024.108939","url":null,"abstract":"<div><h3>Introduction</h3><p>Great strides have been made identifying molecular and genetic changes expressed by various tumor types. These molecular and genetic changes are used as pharmacologic targets for precision treatment using large molecule (LM) proteins with high specificity. Theranostics exploits these LM biomolecules via radiochemistry, creating sensitive diagnostic and therapeutic agents.</p><p>Intravenous (i.v.) LM drugs have an extended biopharmaceutical half-life thus resulting in an insufficient therapeutic index, permitting only palliative brachytherapy due to unacceptably high rates of systemic nontarget radiation doses to normal tissue.</p><p>We employ tumor arteriole embolization isolating a tumor from the systemic circulation, and local intra-arterial (i.a.) infusion to improve uptake of a LM drug within a porcine renal tumor (RT).</p></div><div><h3>Methods</h3><p>In an oncopig RT we assess the in vivo biodistribution of ^99mTc-labeled macroaggregated albumin (MAA) a surrogate for a LM theranostics agent in the RT, kidney, liver, spleen, muscle, blood, and urine. Control animals underwent i.v. infusion and experimental group undergoing arteriography with pseudovascular isolation (PVI) followed by direct i.a. injection.</p></div><div><h3>Results</h3><p>Injected dose per gram (%ID/g) of the LM at 1 min was 86.75 ± 3.76 and remained elevated up to 120 min (89.35 ± 5.77) with i.a. PVI, this increase was statistically significant (SS) compared to i.v. (13.38 ± 1.56 and 12.02 ± 1.05; <em>p</em> = 0.0003 <em>p</em> = 0.0006 at 1 and 120 min respectively). The circulating distribution of LM in the blood was less with i.a. vs i.v. infusion (2.28 ± 0.31 vs 25.17 ± 1.84 for i.v. <em>p</em> = 0.033 at 1 min). Other organs displayed a trend towards less exposure to radiation for i.a. with PVI compared to i.v. which was not SS.</p></div><div><h3>Conclusion</h3><p>PVI followed by i.a. infusion of a LM drug has the potential to significantly increase the first pass uptake within a tumor. This minimally invasive technique can be translated into clinical practice, potentially rendering monoclonal antibody based radioimmunotherapy a viable treatment for renal tumors.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"136 ","pages":"Article 108939"},"PeriodicalIF":3.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141605223","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":"Combining poly-epitope MoonTags and labeled nanobodies for signal amplification in cell-specific PET imaging in vivo","authors":"Katharina S. Höffgen ,&nbsp;Jennifer Dabel ,&nbsp;Christian P. Konken ,&nbsp;Dominic A. Depke ,&nbsp;Sven Hermann ,&nbsp;Wolfgang Dörner ,&nbsp;Sonja Schelhaas ,&nbsp;Michael Schäfers ,&nbsp;Henning D. Mootz","doi":"10.1016/j.nucmedbio.2024.108937","DOIUrl":"10.1016/j.nucmedbio.2024.108937","url":null,"abstract":"<div><p>Immunorecognition provides an excellent basis for targeted imaging techniques covering a wide range from basic research to diagnostics and from single cells to whole organisms. Fluorescence- or radioisotope-labeled antibodies, antibody fragments or nanobodies enable a direct signal readout upon binding and allow for versatile imaging from microscopy to whole-body imaging. However, as the signal intensity directly correlates with the number of labeled antibodies bound to their epitopes (1:1 binding), sensitivity for low-expressing epitopes can be limiting for visualization. For the first time, we developed poly-epitope tags with multiple copies (1 to 7) of a short peptide epitope, specifically the MoonTag, that are recognized by a labeled nanobody and aimed at signal amplification in microscopy and cell-specific PET imaging. In transiently transfected HeLa cells or stably transduced A4573 cells we characterized complex formation and <em>in vitro</em> signal amplification. Indeed, using fluorescently and radioactively labeled nanobodies we found an approximately linear signal amplification with increasing numbers of epitope copies <em>in vitro</em>. To test the poly-epitope approach <em>in vivo</em>, A4573 tumor cells were injected subcutaneously into the shoulder of NSG mice, with A4573 tumor cells expressing a poly-epitope of 7 MoonTags on one side and WT cells on the other side. Using a [⁶⁸Ga]-labeled NODAGA-conjugated MoonTag nanobody, we performed PET/CT imaging at day 8–9 after tumor implantation. Specific binding of a [⁶⁸Ga]-labeled NODAGA-conjugated MoonTag nanobody was observed in 7xMoonTag tumors (1.7 ± 0.5%ID/mL) by PET imaging, showing significantly higher radiotracer accumulation compared to the WT tumors (1.1 ± 0.3%ID/mL; <em>p</em> &lt; 0.01). <em>Ex vivo</em> gamma counter measurements confirmed significantly higher uptake in 7xMoonTag tumors compared to WT tumors (<em>p</em> &lt; 0.001). In addition, MoonTag nanobody binding was detected by autoradiography which was spatially matched with histological analysis of the tumor tissues. In conclusion, we expect nanobody-based poly-epitope tag strategies to be widely applicable for multimodal imaging techniques given the advantageous properties of nanobodies and their amenability to genetic and chemical engineering.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"136 ","pages":"Article 108937"},"PeriodicalIF":3.6,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000635/pdfft?md5=538e2cf736ea2337611b25300b461524&pid=1-s2.0-S0969805124000635-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534953","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)00062-3","DOIUrl":"https://doi.org/10.1016/S0969-8051(24)00062-3","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"134 ","pages":"Article 108936"},"PeriodicalIF":3.1,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000623/pdfft?md5=1734a70dd45da717e492059237c25fc2&pid=1-s2.0-S0969805124000623-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141325735","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 characterization of 64Cu-labeled Geldanamycin derivative for imaging HSP90 expression in breast cancer","authors":"Feng Li ,&nbsp;Yubo Fan ,&nbsp;Lan Zhou ,&nbsp;Diego R. Martin ,&nbsp;Zhonglin Liu ,&nbsp;Zheng Li","doi":"10.1016/j.nucmedbio.2024.108929","DOIUrl":"https://doi.org/10.1016/j.nucmedbio.2024.108929","url":null,"abstract":"<div><p>Heat shock protein 90 (HSP90) plays a crucial role in cancer cell growth and metastasis by stabilizing overexpressed signaling proteins. Inhibiting HSP90 has emerged as a promising anti-cancer strategy. In this study, we aimed to develop and characterize a HSP90-targeted molecular imaging probe, [⁶⁴Cu]Cu-DOTA-BDA-GM, based on a specific HSP90 inhibitor, geldanamycin (GM), for PET imaging of cancers. GM is modified at the C-17 position with 1,4-butane-diamine (BDA) and linked to 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for ⁶⁴Cu radiolabeling. We evaluated the probe's specific binding to HSP90-expressing cells using Chinese hamster ovary (CHO) cells and breast cancer cells including MDA-MB-231, MDA-MB-435S, MCF7, and KR-BR-3 cell lines. A competition study with non-radioactive GM-BDA yielded an IC50 value of 1.35 ± 0.14 nM, underscoring the probe's affinity for HSP90. In xenograft models of MDA-MB-231 breast cancer, [⁶⁴Cu]Cu-DOTA-BDA-GM showcased targeted tumor localization, with significant radioactivity observed up to 18 h post-injection. Blocking studies using unlabeled GM-BDA and treatment with the anticancer drug Vorinostat (SAHA), which can affect the expression and activity of numerous proteins, such as HSPs, confirmed the specificity and sensitivity of the probe in cancer targeting. Additionally, PET/CT imaging in a lung metastasis mouse model revealed increased lung uptake of [⁶⁴Cu]Cu-DOTA-BDA-GM in metastatic sites, significantly higher than in non-metastatic lungs, illustrating the probe's ability to detect metastatic breast cancer. In conclusion, [⁶⁴Cu]Cu-DOTA-BDA-GM represents a sensitive and specific approach for identifying HSP90 expression in breast cancer and metastases, offering promising implications for clinical diagnosis and monitoring.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"136 ","pages":"Article 108929"},"PeriodicalIF":3.1,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097739","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":"Target engagement of an anti-MT1-MMP antibody for triple-negative breast cancer PET imaging and beta therapy","authors":"Natalia Magro ,&nbsp;Marta Oteo ,&nbsp;Eduardo Romero ,&nbsp;Marta Ibáñez-Moragues ,&nbsp;Victor Manuel Lujan ,&nbsp;Laura Martínez ,&nbsp;Oscar Vela ,&nbsp;Maria Elena López-Melero ,&nbsp;Alicia G. Arroyo ,&nbsp;Guillermo Garaulet ,&nbsp;Jorge Luis Martínez-Torrecuadrada ,&nbsp;Francisca Mulero ,&nbsp;Miguel Angel Morcillo","doi":"10.1016/j.nucmedbio.2024.108930","DOIUrl":"10.1016/j.nucmedbio.2024.108930","url":null,"abstract":"<div><h3>Purpose</h3><p>Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks effective diagnostic and therapeutic options. Membrane type 1 matrix metalloproteinase (MT1-MMP) is an attractive biomarker for improving patient selection. This study aimed to develop a theranostic tool using a highly tumour-selective anti-MT1-MMP antibody (LEM2/15) radiolabelled with ⁸⁹Zr for PET and ¹⁷⁷Lu for therapy in a TNBC murine model.</p></div><div><h3>Methods</h3><p>The LEM2/15 antibody and IgG isotype control were radiolabelled with ⁸⁹Zr. PET imaging was performed in a TNBC orthotopic mouse model at 1, 2, 4, and 7 days after administration. Tissue biodistribution and pharmacokinetic parameters were analysed and Patlak linearisation was used to calculate the influx rate of irreversible uptake. The TNBC mice were treated with [¹⁷⁷Lu]Lu-DOTA-LEM2/15 (single- or 3-dose regimen) or saline. Efficacy of [¹⁷⁷Lu]Lu-DOTA-LEM2/15 was evaluated as tumour growth and DNA damage (γH2AX) in MDA 231-BrM2-831 tumours.</p></div><div><h3>Results</h3><p>At 7 days post-injection, PET uptake in tumour xenografts revealed a 1.6-fold and 2.4-fold higher tumour-to-blood ratio for [⁸⁹Zr]Zr-Df-LEM2/15 in the non-blocked group compared to the blocked and IgG isotype control groups, respectively. Specific uptake of LEM2/15 in TBNC tumours mediated by MT1-MMP-binding was demonstrated by the Patlak linearisation method, providing insights into the potential efficacy of LEM2/15-based treatments. A similar uptake was found for [⁸⁹Zr]Zr-Df-LEM2/15 and [¹⁷⁷Lu]Lu-DOTA-LEM2/15 in tumours 7 days post-injection (6.80 ± 1.31 vs. 5.61 ± 0.66 %ID/g). Tumour doubling time was longer in the [¹⁷⁷Lu]Lu-DOTA-LEM2/15 3-dose regimen treated group compared to the control (50 vs. 17 days, respectively). The percentage of cells with γH2AX-foci was higher in tumours treated with [¹⁷⁷Lu]Lu-DOTA-LEM2/15 3-dose regimen compared to tumours non-treated or treated with [¹⁷⁷Lu]Lu-DOTA-LEM2/15 single-dose (12 % vs. 4–5 %).</p></div><div><h3>Conclusions</h3><p>The results showed that the ⁸⁹Zr/¹⁷⁷Lu-labelled anti-MT1-MMP mAb (LEM2/15) pair facilitated immune-PET imaging and reduced tumour growth in a preclinical TNBC xenograft model.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"136 ","pages":"Article 108930"},"PeriodicalIF":3.1,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000568/pdfft?md5=405b7a48670d167c2e5b1df9dbb1e4ce&pid=1-s2.0-S0969805124000568-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141135379","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":"Study of activation cross sections of double neutron capture reaction on 193Ir for the reactor production route of radiotherapeutic 195mPt","authors":"Alexander S. Madumarov ,&nbsp;Nikolay V. Aksenov ,&nbsp;Gospodin A. Bozhikov ,&nbsp;Andrey A. Astakhov ,&nbsp;Yury V. Albin ,&nbsp;Maksim V. Bulavin ,&nbsp;Evgeny P. Shabalin ,&nbsp;Sergey N. Dmitriev","doi":"10.1016/j.nucmedbio.2024.108928","DOIUrl":"https://doi.org/10.1016/j.nucmedbio.2024.108928","url":null,"abstract":"<div><p>The radiotherapeutic ^195mPt is among the most effective Auger electron emitters of the currently studied radionuclides that have a potential theranostic application in nuclear medicine. Production of ^195mPt through double neuron capture of enriched ¹⁹³Ir followed by β⁻-decay to the radioisotope of interest carried out at the research reactor IBR-2 is described. Because of the high radiation background, radiochemical purification procedure of ^195mPt from bulk of iridium was needed to be developed and is detailed here as well. For the first time, cross section and resonance integral for the reaction ¹⁹⁴Ir(n,γ)^195mIr were determined. Resonance neutrons contribution was established to exceed that of thermal neutrons, and resonance integral for the reaction ¹⁹⁴Ir(n,γ)^195mIr is calculated to be 2900 b. Specific activity of ^195mPt was estimated to reach a value of 38.7 GBq/(g Pt) at IBR-2 by the end of bombardment (EOB).</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"134 ","pages":"Article 108928"},"PeriodicalIF":3.1,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141073159","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":"Preclinical evaluation of MC1R targeting theranostic pair [155Tb]Tb-crown-αMSH and [161Tb]Tb-crown-αMSH","authors":"Luke Wharton ,&nbsp;Scott W. McNeil ,&nbsp;Chengcheng Zhang ,&nbsp;Gokce Engudar ,&nbsp;Michiel Van de Voorde ,&nbsp;Jutta Zeisler ,&nbsp;Helena Koniar ,&nbsp;Sathiya Sekar ,&nbsp;Zheliang Yuan ,&nbsp;Paul Schaffer ,&nbsp;Valery Radchenko ,&nbsp;Maarten Ooms ,&nbsp;Peter Kunz ,&nbsp;François Bénard ,&nbsp;Hua Yang","doi":"10.1016/j.nucmedbio.2024.108925","DOIUrl":"10.1016/j.nucmedbio.2024.108925","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Targeted radionuclide therapy is established as a highly effective strategy for the treatment of metastatic tumors; however, the co-development of suitable imaging companions to therapy remains significant challenge. Theranostic isotopes of terbium (&lt;sup&gt;149&lt;/sup&gt;Tb, &lt;sup&gt;152&lt;/sup&gt;Tb, &lt;sup&gt;155&lt;/sup&gt;Tb, &lt;sup&gt;161&lt;/sup&gt;Tb) have the potential to provide chemically identical radionuclidic pairs, which collectively encompass all modes of nuclear decay relevant to nuclear medicine. Herein, we report the first radiochemistry and preclinical studies involving &lt;sup&gt;155&lt;/sup&gt;Tb- and &lt;sup&gt;161&lt;/sup&gt;Tb-labeled crown-αMSH, a small peptide-based bioconjugate suitable for targeting melanoma.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;&lt;sup&gt;155&lt;/sup&gt;Tb was produced via proton induced spallation of Ta targets using the isotope separation and acceleration facility at TRIUMF with isotope separation on-line (ISAC/ISOL). The radiolabeling characteristics of crown-αMSH with &lt;sup&gt;155&lt;/sup&gt;Tb and/or &lt;sup&gt;161&lt;/sup&gt;Tb were evaluated by concentration-dependence radiolabeling studies, and radio-HPLC stability studies. Log&lt;em&gt;D&lt;/em&gt;&lt;sub&gt;7.4&lt;/sub&gt; measurements were obtained for [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-crown-αMSH. Competitive binding assays were undertaken to determine the inhibition constant for [&lt;sup&gt;nat&lt;/sup&gt;Tb]Tb-crown-αMSH in B16-F10 cells. Pre-clinical biodistribution and SPECT/CT imaging studies of &lt;sup&gt;155&lt;/sup&gt;Tb and &lt;sup&gt;161&lt;/sup&gt;Tb labeled crown-αMSH were undertaken in male C57Bl/6 J mice bearing B16-F10 melanoma tumors to evaluate tumor specific uptake and imaging potential for each radionuclide.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Quantitative radiolabeling of crown-αMSH with [&lt;sup&gt;155&lt;/sup&gt;Tb]Tb&lt;sup&gt;3+&lt;/sup&gt; and [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb&lt;sup&gt;3+&lt;/sup&gt; was demonstrated under mild conditions (RT, 10 min) and low chelator concentrations; achieving high molar activities (23–29 MBq/nmol). Radio-HPLC studies showed [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-crown-αMSH maintains excellent radiochemical purity in human serum, while gradual metabolic degradation is observed in mouse serum. Competitive binding assays showed the high affinity of [&lt;sup&gt;nat&lt;/sup&gt;Tb]Tb-crown-αMSH toward MC1R. Two different methods for preparation of the [&lt;sup&gt;155&lt;/sup&gt;Tb]Tb-crown-αMSH radiotracer were investigated and the impacts on the biodistribution profile in tumor bearing mice is compared. Preclinical in vivo studies of &lt;sup&gt;155&lt;/sup&gt;Tb- and &lt;sup&gt;161&lt;/sup&gt;Tb- labeled crown-αMSH were performed in parallel, in mice bearing B16-F10 tumors; where the biodistribution results showed similar tumor specific uptake (6.06–7.44 %IA/g at 2 h pi) and very low uptake in nontarget organs. These results were further corroborated through a series of single-photon emission computed tomography (SPECT) studies, with [&lt;sup&gt;155&lt;/sup&gt;Tb]Tb-crown-αMSH and [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-crown-αMSH showing comparable uptake profiles and excellent image contrast.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;Collectively, our studies highlight the promi","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"136 ","pages":"Article 108925"},"PeriodicalIF":3.1,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141057418","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":"[18F]FMISO-PET imaging reveals the role of hypoxia severity in checkpoint blockade response","authors":"Kaytlyn C. McNeal ,&nbsp;Kirsten M. Reeves ,&nbsp;Patrick N. Song ,&nbsp;Suzanne E. Lapi ,&nbsp;Anna G. Sorace ,&nbsp;Benjamin M. Larimer","doi":"10.1016/j.nucmedbio.2024.108918","DOIUrl":"10.1016/j.nucmedbio.2024.108918","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Context&lt;/h3&gt;&lt;p&gt;Hypoxia within the tumor microenvironment is a critical factor influencing the efficacy of immunotherapy, including immune checkpoint inhibition. Insufficient oxygen supply, characteristic of hypoxia, has been recognized as a central determinant in the progression of various cancers. The reemergence of evofosfamide, a hypoxia-activated prodrug, as a potential treatment strategy has sparked interest in addressing the role of hypoxia in immunotherapy response. This investigation sought to understand the kinetics and heterogeneity of tumor hypoxia and their implications in affecting responses to immunotherapeutic interventions with and without evofosfamide.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;p&gt;This study aimed to investigate the influence of hypoxia on immune checkpoint inhibition, evofosfamide monotherapy, and their combination on colorectal cancer (CRC). Employing positron emission tomography (PET) imaging, we developed novel analytical methods to quantify and characterize tumor hypoxia severity and distribution.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Procedures&lt;/h3&gt;&lt;p&gt;Murine CRC models were longitudinally imaged with [&lt;sup&gt;18&lt;/sup&gt;F]-fluoromisonidazole (FMISO)-PET to quantify tumor hypoxia during checkpoint blockade (anti-CTLA-4 + and anti-PD1 +/− evofosfamide). Metrics including maximum tumor [&lt;sup&gt;18&lt;/sup&gt;F]FMISO uptake (FMISOmax) and mean tumor [&lt;sup&gt;18&lt;/sup&gt;F]FMISO uptake (FMISOmean) were quantified and compared with normal muscle tissue (average muscle FMISO uptake (mAvg) and muscle standard deviation (mSD)). Histogram distributions were used to evaluate heterogeneity of tumor hypoxia.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;p&gt;Severe hypoxia significantly impeded immunotherapy effectiveness consistent with an immunosuppressive microenvironment. Hypoxia-specific PET imaging revealed a striking degree of spatial heterogeneity in tumor hypoxia, with some regions exhibiting significantly more severe hypoxia than others. The study identified FMISOmax as a robust predictor of immunotherapy response, emphasizing the impact of localized severe hypoxia on tumor volume control during therapy. Interestingly, evofosfamide did not directly reduce hypoxia but markedly improved the response to immunotherapy, uncovering an alternative mechanism for its efficacy.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;These results enhance our comprehension of the interplay between hypoxia and immune checkpoint inhibition within the tumor microenvironment, offering crucial insights for the development of personalized cancer treatment strategies. Non-invasive hypoxia quantification through molecular imaging evaluating hypoxia severity may be an effective tool in guiding treatment planning, predicting therapy response, and ultimately improving patient outcomes across diverse cancer types and tumor microenvironments. It sets the stage for the translation of these findings into clinical practice, facilitating the optimization of immunotherapy regimens by addressing tumor hypoxia and thereb","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"134 ","pages":"Article 108918"},"PeriodicalIF":3.1,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141051395","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":"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}