Nuclear medicine and biology最新文献

{"title":"Tracking the fate of bacteria-derived site-specific immunomodulators by positron emission tomography","authors":"Alexia Kirby ,&nbsp;Mojmír Suchý ,&nbsp;Daniel Duan ,&nbsp;Mark Bazett ,&nbsp;Shirin Kalyan ,&nbsp;Adam J. Shuhendler","doi":"10.1016/j.nucmedbio.2024.108908","DOIUrl":"10.1016/j.nucmedbio.2024.108908","url":null,"abstract":"<div><h3>Introduction</h3><p>Site-specific immunomodulators (SSIs) are a novel class of therapeutics made from inactivated bacterial species designed to regulate the innate immune system in targeted organs. QBECO is a gut-targeted SSI that is being advanced clinically to treat and/or prevent inflammatory bowel disease, cancer, and serious infections of the gastrointestinal (GI) tract and proximal organs, and QBKPN is a lung-targeted SSI that is in clinical development for the treatment and/or prevention of chronic inflammatory lung disease, lung cancers and respiratory tract infections. While these SSIs have demonstrated both safety and proof-of-concept in preclinical and clinical studies, detailed understanding of their trafficking and biodistribution is yet to be fully characterized.</p></div><div><h3>Methods</h3><p>QBECO and QBKPN were radiolabeled with [⁸⁹Zr] and injected subcutaneously into healthy mice. The mice underwent Positron Emission Tomography (PET) imaging every day for eight days to track biodistribution of the SSIs. Tissue from the site of injection was collected and immunohistologically probed for immune cell infiltration.</p></div><div><h3>Results</h3><p>Differential biodistribution of the two SSIs was seen, adhering to their site-specific targeting. QBKPN appeared to migrate from the site of injection (abdomen) to the cervical lymph nodes which are nearer to the respiratory tract and lungs. QBECO remained in the abdominal region, with lymphatic trafficking to the inguinal lymph nodes, which are nearer to GI-proximal tissues/organs. Immune infiltration at the site of injection comprised of neutrophils for both SSIs, and macrophages for only QBKPN.</p></div><div><h3>Conclusion</h3><p>Radiolabeling of SSIs allows for longitudinal <em>in vivo</em> imaging of biodistribution and trafficking. PET imaging revealed differential biodistribution of the SSIs based on the organotropism of the bacteria from which the SSI is derived. Trafficking from the site of injection to the targeted site is in part mediated <em>via</em> the lymphatics and involves macrophages and neutrophils.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"132 ","pages":"Article 108908"},"PeriodicalIF":3.1,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000349/pdfft?md5=803553e48cb11ad46108b40bfb9a77cd&pid=1-s2.0-S0969805124000349-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140399091","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":"The future of the radiopharmaceutical sciences","authors":"Suzanne E. Lapi ,&nbsp;Peter J.H. Scott","doi":"10.1016/j.nucmedbio.2024.108907","DOIUrl":"10.1016/j.nucmedbio.2024.108907","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"132 ","pages":"Article 108907"},"PeriodicalIF":3.1,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140405270","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":"Investigation of imaging the somatostatin receptor by opening the blood-brain barrier with melittin – A feasibility study using positron emission tomography and [64Cu]Cu-DOTATATE","authors":"Ida Vang Andersen ,&nbsp;Natasha Shalina Rajani Bidesi ,&nbsp;Vladimir Shalgunov ,&nbsp;Jesper Tranekjær Jørgensen ,&nbsp;Tobias Gustavsson ,&nbsp;Kristian Strømgaard ,&nbsp;Andreas T. Ingemann Jensen ,&nbsp;Andreas Kjær ,&nbsp;Matthias M. Herth","doi":"10.1016/j.nucmedbio.2024.108905","DOIUrl":"10.1016/j.nucmedbio.2024.108905","url":null,"abstract":"<div><p>DOTATATE is a somatostatin peptide analog used in the clinic to detect somatostatin receptors which are highly expressed on neuroendocrine tumors. Somatostatin receptors are found naturally in the intestines, pancreas, lungs, and brain (mainly cortex). <em>In vivo</em> measurement of the somatostatin receptors in the cortex has been challenging because available tracers cannot cross the blood-brain barrier (BBB) due to their intrinsic polarity. A peptide called melittin, a main component of honeybee venom, has been shown to disrupt plasma membranes and increase the permeability of biological membranes. In this study, we assessed the feasibility of using melittin to facilitate the passage of [⁶⁴Cu]Cu-DOTATATE through the BBB and its binding to somatostatin receptors in the cortex. Evaluation included <em>in vitro</em> autoradiography on Long Evans rat brains to estimate the binding affinity of [⁶⁴Cu]Cu-DOTATATE to the somatostatin receptors in the cortex and an <em>in vivo</em> evaluation of [⁶⁴Cu]Cu-DOTATATE binding in NMRI mice after injection of melittin. This study found an <em>in vitro</em> B_max = 89 ± 4 nM and K_D = 4.5 ± 0.6 nM in the cortex, resulting in a theoretical binding potential (BP) calculated as B_max/K_D ≈ 20, which is believed suitable for <em>in vivo</em> brain PET imaging. However, the <em>in vivo</em> results showed no significant difference between the control and melittin injected mice, indicating that the honeybee venom failed to open the BBB. Additional experiments, potentially involving faster injection rates are required to verify that melittin can increase brain uptake of non-BBB permeable PET tracers. Furthermore, an evaluation of whether a venom with a narrow therapeutic range can be used for clinical purposes needs to be considered.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"132 ","pages":"Article 108905"},"PeriodicalIF":3.1,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000313/pdfft?md5=3174fbf20b7357dacd7f363af0d97b77&pid=1-s2.0-S0969805124000313-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140170298","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":"Second generation Al18F-labeled D-amino acid peptide for CXCR4 targeted molecular imaging","authors":"Muriel Aline Spahn ,&nbsp;Kaat Luyten ,&nbsp;Tom Van Loy ,&nbsp;Mike Sathekge ,&nbsp;Christophe M. Deroose ,&nbsp;Michel Koole ,&nbsp;Dominique Schols ,&nbsp;Wim Vanduffel ,&nbsp;Kristof De Vos ,&nbsp;Pieter Annaert ,&nbsp;Guy Bormans ,&nbsp;Frederik Cleeren","doi":"10.1016/j.nucmedbio.2024.108906","DOIUrl":"10.1016/j.nucmedbio.2024.108906","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;The C-X-C chemokine receptor type 4 (CXCR4) is overexpressed in many cancers, &lt;em&gt;e.g.&lt;/em&gt; multiple myeloma and acute leukemia, yet solely [&lt;sup&gt;68&lt;/sup&gt;Ga]PentixaFor is used for clinical PET imaging. The aim of this study was to develop and assess a second generation Al&lt;sup&gt;18&lt;/sup&gt;F-labeled D-amino acid peptide based on the viral macrophage inflammatory protein II for CXCR4 targeted molecular imaging.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;We designed a library of monomer and multimer constructs and evaluated their binding affinity for human and mouse CXCR4. Based on these results, we selected the best vector molecule for development of an Al&lt;sup&gt;18&lt;/sup&gt;F-labeled ligand, [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-2xDV1(c11sc12s), which was further evaluated in a cell-based binding assay to assess its binding properties and specificity for CXCR4. Next, pharmacokinetics and tumor uptake of [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-2xDV1(c11sc12s) were evaluated in naïve mice and mice with xenografts derived from U87.CXCR4 cells. Finally, we performed an imaging study in a non-human primate to assess the &lt;em&gt;in vivo&lt;/em&gt; distribution of this novel radioligand in a species closely related to humans.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The lead ligand AlF-NOTA-2xDV1(c11sc12s) showed six-fold higher affinity for human CXCR4 compared to Ga-Pentixafor. The corresponding radiotracer was obtained in a good radiochemical yield of 40.1 ± 13.5 % (&lt;em&gt;n&lt;/em&gt; = 4) and apparent molar activity of 20.4 ± 3.3 MBq/nmol (n = 4) after optimization. In U87.CD4.CXCR4 cell binding assays, the total bound fraction of [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-(2×)DV1(c11sc12s) was 32.4 ± 1.8 %. This fraction could be reduced by 82.5 % in the presence of 75 μM AMD3100. In naïve mice, [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-2xDV1(c11sc12s) accumulated in organs expressing mouse CXCR4, &lt;em&gt;e.g.&lt;/em&gt; the liver (SUV&lt;sub&gt;mean&lt;/sub&gt; (mean standardized uptake value) 75 min p.i. 11.7 ± 0.6), which was blockable by co-injecting AMD3100 (5 mg/kg). In U87.CXCR4 xenografted tumor mice, the tumor uptake of [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-2xDV1(c11sc12s) remained low (SUV&lt;sub&gt;mean&lt;/sub&gt; 0.5 ± 0.1), but was reduced by co-administration of AMD3100. Surprisingly, [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-2xDV1(c11sc12s) exhibited a similar biodistribution in a non-human primate as in mice indicating off-target binding of [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-2xDV1(c11sc12s) in liver tissue. We confirmed that [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-2xDV1(c11sc12s) is taken up by hepatocytes using &lt;em&gt;in vitro&lt;/em&gt; studies and that the uptake can be blocked with AMD3100 and rifampicin, a potent organic anion-transporting-polypeptide (OATP)1B1 and OATP1B3 inhibitor.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;The second generation D-peptide AlF-NOTA-2xDV1(c11sc12s) showed high affinity for human CXCR4 and the corresponding radiotracer was produced in good radiochemical yields. However, [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-2xDV1(c11sc12s) is not specific for CXCR4 and is also a substrate for OATP1B1 and/or OA","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"132 ","pages":"Article 108906"},"PeriodicalIF":3.1,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140170269","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 acute intravenous toxicity of HEPES: Is Good's buffer good and safe enough for clinical utilization in nuclear medicine?","authors":"Mohini Guleria ,&nbsp;K.J. Pallavi ,&nbsp;Pranjal P. Gujarathi ,&nbsp;Tapas Das","doi":"10.1016/j.nucmedbio.2024.108895","DOIUrl":"10.1016/j.nucmedbio.2024.108895","url":null,"abstract":"<div><h3>Objective</h3><p>Good's buffer or HEPES has advantages over other buffers commonly used in radiopharmaceutical preparation as it exhibits significantly lower complexation tendency with metal ions. However, use of HEPES buffer for radiolabeling reactions, meant for clinical applications, has been underrated due to the non-availability of sufficient toxicity data. The objective of the present study is to find the evidences towards safety of intravenous administration of HEPES through systemic toxicological studies in small animal model to support its safe application for clinical exploitation.</p></div><div><h3>Experimental</h3><p>A pilot study was performed to investigate the lethal dose of HEPES in female Sprague Dawley rats by administering seven different doses of HEPES solution (150 to 2000 mg/kg), through intravenous pathway. Similarly, for determining maximum tolerated dose (MTD), gradually increasing doses of HEPES (50 to 950 mg/kg) were administered in the same species via similar pathway. Various hematological and clinical pathological investigations were carried out in order to find out the safe administration dose of HEPES in rats.</p></div><div><h3>Results</h3><p>No mortality was observed up to 2000 mg/kg doses of HEPES. The doses beyond 300 mg/kg resulted few temporary adverse effects, though these were found to disappear within 4–5 days of dosing.</p></div><div><h3>Conclusion</h3><p>The amount of HEPES to be administered during clinical intervention is usually much lower (typically 1–2.5 mg per kg of body weight of healthy adult) than the MTD determined in rat model during present report. Hence, the utilization of this buffer for preparation of radiolabeled drugs for human investigation may be safe. However, further detailed investigations may be warranted for supporting the candidature of Good's buffer for regular clinical exploitation.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"132 ","pages":"Article 108895"},"PeriodicalIF":3.1,"publicationDate":"2024-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140074333","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":"Improved purification of cyclotron [68Ga]GaCl3 for the production of 68Ga radiopharmaceuticals","authors":"Ivan E. Wang,&nbsp;Allen F. Brooks,&nbsp;Mara Clark,&nbsp;Luke J. Morrissette,&nbsp;Peter J.H. Scott","doi":"10.1016/j.nucmedbio.2024.108892","DOIUrl":"10.1016/j.nucmedbio.2024.108892","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;Increased demand for NetSpot and Illuccix as requirement to receive the respective Lutathera and Pluvicto radiotherapies, and monitor subsequent response to treatment, have reinforced the need to develop alternative ways of producing gallium-68 (&lt;sup&gt;68&lt;/sup&gt;Ga). Building on our efforts to produce &lt;sup&gt;68&lt;/sup&gt;Ga in a liquid target on a GE PETtrace, the goal of this work is to modify the current GE Gallium Chloride cassette using the FASTLab 2 synthesis module to produce [&lt;sup&gt;68&lt;/sup&gt;Ga]GaCl&lt;sub&gt;3&lt;/sub&gt; equivalent to a 1.85 GBq generator and demonstrate compatibility with FDA-approved kits for production of &lt;sup&gt;68&lt;/sup&gt;Ga-labeled radiopharmaceuticals.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;&lt;sup&gt;68&lt;/sup&gt;Ga was produced in a liquid target via the &lt;sup&gt;68&lt;/sup&gt;Zn(p,n)&lt;sup&gt;68&lt;/sup&gt;Ga reaction. &lt;sup&gt;68&lt;/sup&gt;Ga was loaded onto various sizes of ZR resins (ZR Load, 0.3 mL, 1 mL, or 2 mL). The loading efficiency was determined using a dose calibrator. After washing with HNO&lt;sub&gt;3&lt;/sub&gt;, 1.75 M HCl was used to elute the ZR Load resin through various sizes of a second ZR resin (ZR CG, 0 mL, 2 mL, 4 mL). Using 0.5 mL fractions, the elution profile was determined. Compatibility of the [&lt;sup&gt;68&lt;/sup&gt;Ga]GaCl&lt;sub&gt;3&lt;/sub&gt; with NetSpot and Illuccix kits was investigated. Radiochemical purity (RCP) and 4 h stability were determined using radioTLC and radioHPLC. Using a modified [&lt;sup&gt;68&lt;/sup&gt;Ga]GaCl&lt;sub&gt;3&lt;/sub&gt; cassette and new FASTLab program, 6 validation preparations were conducted using NetSpot and Illuccix kits for which RCP, stability, sterility and suitability were determined. Dual irradiation of 2 liquid targets was also performed, which was used to simultaneously prepare 1 NetSpot and 2 Illuccix kits by diluting the required activity with 0.1 M HCl.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The commercially available GE Cassette gave low RCP using commercial FDA kits. To optimize this, the loading efficiency onto ZR Load and the ratio of ZR resin used to load the initial activity and subsequent elution were explored. When using a 2:4 ratio of ZR Load to ZR CG, 97.89 % RCP was observed when a 3.8 mL [&lt;sup&gt;68&lt;/sup&gt;Ga]GaCl&lt;sub&gt;3&lt;/sub&gt; solution was used. For Dotatate validation, 0.55 mL of buffer was added to 4.2 mL of [&lt;sup&gt;68&lt;/sup&gt;Ga]GaCl&lt;sub&gt;3&lt;/sub&gt; which gave 1.35 GBq of formulated product. For Illuccix validation, [&lt;sup&gt;68&lt;/sup&gt;Ga]GaCl&lt;sub&gt;3&lt;/sub&gt; was added to 2.5 mL of buffer which gave 1.52 GBq of [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-PSMA-11. Formulated products passed package insert quality control (QC) requirements. When dual target irradiations were performed, 2.84 GBq was delivered to an external vial and used to label 1 NetSpot and 2 Illuccix kits simultaneously, and each kit also met or exceeded established QC criteria.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;Methods are reported for using cyclotron-produced &lt;sup&gt;68&lt;/sup&gt;Ga from a liquid target in conjunction with FDA-approved NetSpot and Illucix kits. By employing a 2 mL ZR Load resin with a 4 mL ZR C","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"130 ","pages":"Article 108892"},"PeriodicalIF":3.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139979653","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)00028-3","DOIUrl":"https://doi.org/10.1016/S0969-8051(24)00028-3","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"130 ","pages":"Article 108902"},"PeriodicalIF":3.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000283/pdfft?md5=7750bfbf9380ad160e2878fe8f0c985b&pid=1-s2.0-S0969805124000283-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186984","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":"In vitro evaluation of [3H]PI-2620 and structural derivatives in non-Alzheimer's tauopathies","authors":"Cassis Varlow ,&nbsp;Chester A. Mathis ,&nbsp;Neil Vasdev","doi":"10.1016/j.nucmedbio.2024.108891","DOIUrl":"10.1016/j.nucmedbio.2024.108891","url":null,"abstract":"<div><p>Alzheimer's disease (AD) and non-AD tauopathies such as chronic traumatic encephalopathy (CTE), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) are characterized by the abnormal aggregation of three-repeat (3R) and/or four-repeat (4R) tau isoforms. Several tau-PET tracers have been applied for human imaging of AD and non-AD tauopathies including [¹⁸F]PI-2620. Our objective is to evaluate [³H]PI-2620 and two promising structural derivatives, [³H]PI-2014 and [³H]F-4, using in vitro saturation assays and competitive binding assays against new chemical entities based on this scaffold in human AD tissues for comparison with PSP, CBD and CTE tissues. Thin section autoradiography was employed to assess specific binding and distribution of [³H]PI-2620 and [³H]F-4 in fresh-frozen human post-mortem AD, PSP, CBD and CTE tissues. Immunohistochemistry was performed for phospho-tau (AT8) and 4R-tau (RD4). Homogenate filtration binding assays were performed for saturation analysis and competitive binding studies against [³H]PI-2620. All compounds bound with high affinity in AD tissue. In PSP tissue [³H]PI-2620 demonstrated the highest affinity (5.3 nM) and in CBD tissue [³H]F-4 bound with the highest affinity (9.4 nM). Over 40 fluorinated derivatives based on PI-2620 and F-4 were screened in AD and PSP tissue. Notably, compound <strong>2</strong> was the most potent derivative in PSP tissue (K_i = 7.3 nM). By autoradiography, [³H]PI-2620 and [³H]F-4 demonstrated positive signals similar in intensity in AD, PSP and CTE tissues that were displaced by homologous blockade. Binding of both radiotracers aligned with immunostaining for 4R-tau. This work demonstrates that [³H]PI-2620 and [³H]F-4 show promise for imaging 4R-tau aggregates in non-AD tauopathies. PI-2620 continues to serve as a structural scaffold for PET radiotracers with higher affinity for non-AD tau over AD tau.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"130 ","pages":"Article 108891"},"PeriodicalIF":3.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000179/pdfft?md5=912a8d6c3b336c5220b2911bae51f86d&pid=1-s2.0-S0969805124000179-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139925442","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":"Serotonin transporter imaging agent as a probe for β-cells of pancreas","authors":"Yuli Sun ,&nbsp;Guangwen Li ,&nbsp;Haiyan Hong ,&nbsp;Lin Zhu ,&nbsp;Hank F. Kung ,&nbsp;Yan Zhang ,&nbsp;Jinxia Zhu","doi":"10.1016/j.nucmedbio.2024.108894","DOIUrl":"10.1016/j.nucmedbio.2024.108894","url":null,"abstract":"<div><h3>Objective</h3><p>Diabetes mellitus (DM) is one of the major diseases in the world. Nuclear medicine imaging may be able to detect functional status of pancreatic β cells <em>in vivo</em>, which might elucidate the pathological mechanisms of diabetes and develop individualized treatment plans. In this study, we evaluated the ability of [¹²⁵I]ADAM, a serotonin transporter (SERT) imaging agent, as a probe for detecting pancreatic β-cell mass (BCM).</p></div><div><h3>Methods</h3><p><em>In vitro</em> cell studies were evaluated in INS-1 cells (rat islet β cell line). Biodistribution studies were performed in male normal Sprague-Dawley rats and alloxan-induced type 1 diabetes mellitus (T1DM) rats. Distribution and expression of SERT protein in pancreas of rats were also measured by immunofluorescence staining and Western blot.</p></div><div><h3>Results</h3><p><em>In vitro</em> cell studies showed that the concentration of [¹²⁵I]ADAM associated with the INS-1 cells was increased gradually with incubation time, and the SERT specific inhibitor, escitalopram, exhibited the inhibitory effect on this interaction. Biodistribution studies also showed that the uptake of [¹²⁵I]ADAM in the pancreas of normal rats was decreased in the presence of escitalopram. However, in the T1DM rat model with a significant β cells reduction, the uptake of pancreas was increased when compared with the control. Through immunofluorescence staining and Western blot, it was found that both the endocrine and exocrine cells of the normal pancreas expressed SERT protein, and the level of SERT protein in the exocrine cells was higher than islets. In the diabetic state, the expression of SERT in the exocrine cells was further increased.</p></div><div><h3>Conclusions</h3><p>The SERT imaging agent, [¹²⁵I]ADAM, at the present form will not be suitable for imaging β cells, specifically because there were extraordinarily high non-specific signals contributing from the exocrine cells of pancreas. In addition, we noticed that the level of SERT expression was abnormally elevated in the diabetic state, which might provide an unexpected target for studying the pathological mechanisms of diabetes.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"130 ","pages":"Article 108894"},"PeriodicalIF":3.1,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139979734","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 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}