Nuclear medicine and biology最新文献

{"title":"[18F]BCPP-EF positron emission tomography of rat ovaries for evaluation of mitochondrial function","authors":"Yuki Tomonari,&nbsp;Hiroyuki Ohba,&nbsp;Hideo Tsukada","doi":"10.1016/j.nucmedbio.2025.108996","DOIUrl":"10.1016/j.nucmedbio.2025.108996","url":null,"abstract":"<div><h3>Background</h3><div>The ovary is an important female organ not only for pregnancy but also for the regulation of life activities via hormone release. Ovarian function is measured by blood hormone levels, but the hormone level reflects only the ovarian reserve and no other essential ovarian functions, such as nurturing and expelling follicles. Ovarian fibrosis is related to essential ovarian function; however, the existing methods for evaluating fibrosis are invasive. Ovarian fibrosis has been reported to be associated with mitochondrial function. We hypothesized that positron emission tomography (PET) imaging of mitochondria could be a new, non-invasive method for evaluating essential ovarian function. In this study, we investigated the age-related changes in ovarian fibrosis using the mitochondrial complex-I (MC-I) PET probe, 2-<em>tert</em>-butyl-4-chloro-5-{6-[2-(2-¹⁸F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([¹⁸F]BCPP-EF).</div></div><div><h3>Results</h3><div>Aged rats, whose ovary function decline, exhibited a higher uptake of [¹⁸F]BCPP-EF in the ovary than young rats, and this high uptake in aged rats was suppressed by mitoquinone, a superoxide scavenger. Increased [¹⁸F]BCPP-EF uptake in the ovary was associated with ovarian fibrosis, but not with AMH level which reflects the ovarian reserve. Furthermore, the measurement of MC protein levels showed that the protein levels of MC-I increased with age, whereas those of MC-V decreased.</div></div><div><h3>Conclusions</h3><div>This study demonstrated that [¹⁸F]BCPP-EF can detect age-related changes in essential ovarian function evaluated by ovarian fibrosis. Therefore, [¹⁸F]BCPP-EF-PET is a useful non-invasive method for evaluating essential ovarian functions and will contribute to basic research on ovarian aging as well as drug discovery targeting ovarian dysfunction.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142 ","pages":"Article 108996"},"PeriodicalIF":3.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040129","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":"Cross sections of the 226Ra(p,xn) reactions relevant for 225Ac production","authors":"Ondřej Lebeda,&nbsp;Kateřina Ondrák Fialová,&nbsp;Lukáš Ondrák,&nbsp;Jaroslav Červenák,&nbsp;Jan Ráliš,&nbsp;Jan Štursa","doi":"10.1016/j.nucmedbio.2025.108995","DOIUrl":"10.1016/j.nucmedbio.2025.108995","url":null,"abstract":"<div><div>Limited availability constrains the implementation of ²²⁵Ac, the most promising α emitter for targeted therapy, in clinical practice. Proton activation of ²²⁶Ra is one of few realistic solutions to this problem. We have therefore measured cross sections of relevant ²²⁶Ra(<em>p,xn</em>) nuclear reactions in the energy range of 12.0 to 17.2 MeV. The obtained results allowed us to deduce the yield of ²²⁴Ac, ²²⁵Ac, and ²²⁶Ac. The consequences of our data to predictions of production capacity and radionuclidic purity of ²²⁵Ac are thoroughly discussed, and their comparison with previous measurements and with the prediction of the TALYS 1.96 nuclear reaction model code run with default parameters are provided.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142 ","pages":"Article 108995"},"PeriodicalIF":3.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029254","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":"First-in-human healthy volunteer dosimetry studies of the excitatory amino acid transporter 2 (EAAT2) PET imaging tracer methyl N4-(7-[18F]fluoro-9H-fluoren-2-yl)asparaginate, [18F]RP-115","authors":"Chih-Kai Chao ,&nbsp;Joseph Blecha ,&nbsp;Ilona Polvoy ,&nbsp;Ryan Michael Nillo ,&nbsp;Youngho Seo ,&nbsp;David M. Wilson ,&nbsp;John R. Forsayeth ,&nbsp;Henry F. VanBrocklin ,&nbsp;John M. Gerdes","doi":"10.1016/j.nucmedbio.2025.108992","DOIUrl":"10.1016/j.nucmedbio.2025.108992","url":null,"abstract":"<div><h3>Objective and background</h3><div>The objective of this first-in-human study was to investigate the radiosynthesis, and the preliminary safety, biodistribution, and organ radiation dosimetry of the positron emission tomography (PET) imaging tracer methyl <em>N</em>⁴-([¹⁸F]7-fluoro-9<em>H</em>-fluoren-2-yl)asparaginate, known as [¹⁸F]RP-115, in a small cohort (n=8) of healthy volunteers. The [¹⁸F]RP-115 tracer is a methyl ester prodrug and undergoes metabolic saponification in the central nervous system to generate the corresponding carboxylic acid form that selectively binds to the excitatory amino acid transporter 2 (EAAT2) protein.</div></div><div><h3>Procedures and methods</h3><div>A multi-step high molar activity tracer radiosynthesis was devised to produce doses. Eight healthy human participants (four male and four female), aged 56–75, received a bolus intravenous injection of [¹⁸F]RP-115 (administered activity range: 70.3–355 MBq) prior to a total of 94 min of PET-MR scanning performed as three sequential scanning sessions. Regional tissue volumes of interest were defined, time-integrated activity coefficients (TIAC) were derived, and then estimates of organ and tissue activities and effective doses (whole body) were calculated, with two versions of OLINDA software (1.1 and 2.0) that incorporated two tissue weighting factor sets (ICRP-60 and -103), respectively.</div></div><div><h3>Main findings</h3><div>Tracer was routinely produced in good radiochemical yields and as suitable high molar activity doses for injection. The [¹⁸F]RP-115 injections and PET-MR scans were well-tolerated and no adverse events were reported (≤48 h). Radioactivity was widely biodistributed with good organ uptake. TIACs and estimated radiation organ doses were determined, for which a few statistically significant estimated organ dose differences between males and females were noted. The kidneys were identified as the critical target organ.</div></div><div><h3>Principal conclusions</h3><div>Injection of [¹⁸F]RP-115 was considered safe. The estimated kidney radiation doses relative to administered radioactivity identified a more optimal human [¹⁸F]RP-115 tracer injected amount of &lt;211 MBq. This more optimal [¹⁸F]RP-115 tracer injected activity definition is similar to the amounts used for other established [¹⁸F]labeled clinical PET tracers such as [¹⁸F]FDG, and it will be used in future RP-115 clinical PET imaging studies.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142 ","pages":"Article 108992"},"PeriodicalIF":3.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143328928","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":"Characterization of a novel PET radioligand for mitochondrial complex I in nonhuman primate","authors":"Yulong Xu ,&nbsp;Yiming Xu ,&nbsp;Frederick Andrew Bagdasarian ,&nbsp;Tewodros Mulugeta Dagnew ,&nbsp;Hua Cheng ,&nbsp;Yanli Wang ,&nbsp;Yongle Wang ,&nbsp;Leyi Kang ,&nbsp;Hsiao-Ying Wey ,&nbsp;Can Zhang ,&nbsp;Shijun Zhang ,&nbsp;Changning Wang","doi":"10.1016/j.nucmedbio.2025.108993","DOIUrl":"10.1016/j.nucmedbio.2025.108993","url":null,"abstract":"<div><div>The role of mitochondrial complex I (MC-I) dysfunction is well-documented across a range of neurodegenerative disorders. Recently, a novel positron emission tomography (PET) radioligand, [¹⁸F]CNL02, has been synthesized to target MC-I. In this paper, we provide a comprehensive characterization of [¹⁸F]CNL02, using nonhuman primate as a model system. In the brain of a rhesus macaque, [¹⁸F]CNL02 demonstrated specific binding in regions expressing MC-I. All observed brain regions showed rapid kinetic profiles. Analysis of arterial plasma indicated a swift clearance of [¹⁸F]CNL02 from the bloodstream. Metabolite analysis identified two predominant radiometabolites in the plasma. The regional brain time-activity curves (TACs) for [¹⁸F]CNL02 were effectively characterized through a two-tissue compartment model (2TCM). Furthermore, the total distribution volume was reliably estimated employing the Logan plot method. Consequently, continued development and refinement of [¹⁸F]CNL02 are imperative.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142 ","pages":"Article 108993"},"PeriodicalIF":3.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009022","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 68Ga-labeled folic acid conjugates for visualization of inflammatory foci","authors":"Kristina A. Petrosova ,&nbsp;Aleksandr S. Lunev ,&nbsp;Marat G. Rakhimov ,&nbsp;Aleksey E. Machulkin ,&nbsp;Natalia S. Volkova ,&nbsp;Fedor I. Vasilevich ,&nbsp;Anton A. Larenkov","doi":"10.1016/j.nucmedbio.2024.108991","DOIUrl":"10.1016/j.nucmedbio.2024.108991","url":null,"abstract":"<div><h3>Introduction</h3><div>Folate receptors (FR) have been considered a convenient target for different radiopharmaceuticals in recent years. Multifarious ⁶⁸Ga-labeled folate conjugates have been proposed as promising agents for the PET imaging of FR-overexpressing malignant neoplasms. In addition, radiolabeled folate-based conjugates can be effective for imaging non-tumor pathological foci characterized by a pronounced cluster of activated macrophages. We previously reported that a conjugate of folic acid with the NODAGA-chelator, labeled with gallium-68 and containing a (His-Glu)₂-tag ([⁶⁸Ga]Ga-NODAGA-[Lys-(HE)₂]-folic acid), is suitable for imaging tumor lesions characterized by an increased density of FR. Introduction of the (His-Glu)₂-tag into the structure of the folate radioconjugate significantly reduced its accumulation in non-target tissues (e.g., kidneys), leaving the accumulation in tumors at least at the same level, and even increasing it. The present study assessed the suitability of the developed molecule (in comparison with the unmodified analog) for imaging foci of non-oncological etiology characterized by a pronounced macrophage response.</div></div><div><h3>Methods</h3><div>Systemic juvenile idiopathic arthritis (JIA), reproduced in Wistar rats, was used as the pathology model. Acute inflammatory processes of soft tissues of septic and aseptic etiologies were selected as differential models.</div></div><div><h3>Results</h3><div>The results obtained in this study showed a significantly elevated level of accumulation in the JIA focus compared to healthy rat paws and accumulation in the foci of differential models of the inflammatory process, which confirms the macrophage-mediated pathway of accumulation of the studied compounds. Simultaneously, the ratio of accumulation in pathology to accumulation in comparable healthy tissues in all studied pathologies was significantly high.</div></div><div><h3>Conclusion</h3><div>The data obtained allowed us to conclude the diagnostic potential of new radiolabeled folate-based conjugate with (His-Glu)₂-tag for pharmacokinetic property optimization in the radionuclide diagnosis of rheumatoid and other diseases characterized by a pronounced macrophage immune response. The mathematical compartment model quantitatively confirmed that the additional (His-Glu)₂ fragment introduced in the molecule acts in favor of potential radiopharmaceutical use to visualize inflammatory processes by positron emission tomography.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142 ","pages":"Article 108991"},"PeriodicalIF":3.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009037","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":"Optimization and scale-up of [68Ga]Ga-FAPI-46 production on a Modular-Lab PharmTracer platform for clinical application","authors":"Irene Brusa ,&nbsp;Veronica Serena Cabitza ,&nbsp;Stefano Emiliani ,&nbsp;Claudio Malizia ,&nbsp;Emilia Fortunati ,&nbsp;Lucia Zanoni ,&nbsp;Giulia Cuzzani ,&nbsp;Andrea Farolfi ,&nbsp;Paolo Castellucci ,&nbsp;Cristina Nanni ,&nbsp;Stefano Fanti ,&nbsp;Filippo Lodi","doi":"10.1016/j.nucmedbio.2024.108974","DOIUrl":"10.1016/j.nucmedbio.2024.108974","url":null,"abstract":"<div><h3>Background</h3><div>Due to the increasing application of the fibroblast activation protein (FAP) targeting radiotracer [⁶⁸Ga]Ga-FAPI-46 in cancer diagnostics by PET/CT, there is a need for a convenient way for routine production of high activities of this tracer. The aim of the current work is the optimization and scale-up of an automated method for [⁶⁸Ga]Ga-FAPI-46 production on a PharmTracer module using two GalliaPharm generators.</div></div><div><h3>Results</h3><div>Several labeling conditions were evaluated and the best results were obtained with 40 μg of precursor, 3 mg ascorbic acid as anti-radiolysis agent, 0.4 M sodium acetate buffer pH 4.5 and 15 min heating at 95 °C. Furthermore, Vitamin C was added to the final formulation as stabilizer to ensure product quality in a time frame of 3 h after the end of synthesis. The evaluation of 43 routine syntheses of [⁶⁸Ga]Ga-FAPI-46 resulted in a decay-corrected yield of 91.1 ± 3.4 % and radiochemical purity of 99.8 ± 0.3 % as determined by radio-HPLC. All the quality control parameters were in accordance with specifications.</div></div><div><h3>Conclusions</h3><div>In conclusion, we developed an efficient and robust method able to provide multiple doses of [⁶⁸Ga]Ga-FAPI-46, enabling a better response to the clinical need for this radiopharmaceutical.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"140 ","pages":"Article 108974"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478541","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(25)00016-2","DOIUrl":"10.1016/S0969-8051(25)00016-2","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"140 ","pages":"Article 109007"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592509","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":"Alpha Atlas: Mapping global production of α-emitting radionuclides for targeted alpha therapy","authors":"Marianna Tosato ,&nbsp;Chiara Favaretto ,&nbsp;Janke Kleynhans ,&nbsp;Andrew R. Burgoyne ,&nbsp;Jean-François Gestin ,&nbsp;Nicholas P. van der Meulen ,&nbsp;Amirreza Jalilian ,&nbsp;Ulli Köster ,&nbsp;Mattia Asti ,&nbsp;Valery Radchenko","doi":"10.1016/j.nucmedbio.2024.108990","DOIUrl":"10.1016/j.nucmedbio.2024.108990","url":null,"abstract":"<div><div>Targeted Alpha Therapy has shown great promise in cancer treatment, sparking significant interest over recent decades. However, its broad adoption has been impeded by the scarcity of alpha-emitters and the complexities related to their use. The availability of these radionuclides is often constrained by the intricate production processes and purification, as well as regulatory and logistical challenges. Moreover, the high cost and technical difficulties associated with handling and applying alpha-emitting radionuclides pose additional barriers to their clinical implementation.</div><div>This Alpha Atlas provides an in-depth overview of the leading alpha-particle emitting radionuclide candidates for clinical use, focusing on their production processes and supply chains. By mapping the current facilities that produce and supply these radionuclides, this atlas aims to assist researchers, clinicians, and industries in initiating or scaling up the applications of alpha-emitters. The Alpha Atlas aspires to act as a strategic guide, facilitating collaboration and driving forward the integration of these potent therapeutic agents into cancer treatment practices.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142 ","pages":"Article 108990"},"PeriodicalIF":3.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984278","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":"Solid phase extraction chromatography-based radiochemical isolation of cyclotron-produced 51Mn from enriched 54Fe targets","authors":"Kendall E. Barrett ,&nbsp;Jason C. Mixdorf ,&nbsp;Johan Svedjehed ,&nbsp;Jeanine Batterton ,&nbsp;Jennifer Eagleburger ,&nbsp;Yongjun Yan ,&nbsp;Katherine Gagnon ,&nbsp;Eduardo Aluicio-Sarduy ,&nbsp;Todd E. Barnhart ,&nbsp;Jonathan W. Engle","doi":"10.1016/j.nucmedbio.2024.108989","DOIUrl":"10.1016/j.nucmedbio.2024.108989","url":null,"abstract":"<div><div>We report DGA extraction chromatography isolation of ⁵¹Mn from isotopically enriched ⁵⁴Fe. The method has been studied in semi-automated and automated realizations. The former achieves a decay corrected radiochemical yield of 78 ± 1 % (<em>n</em> = 3) and a separation factor of (1.0 ± 0.8) x 10⁵ (n = 3). With GE HealthCare's Solid Target Platform (STP) and FASTlab the latter, fully automated method achieves a decay corrected radiochemical yield of 87 ± 1 % (<em>n</em> = 3) and a separation factor of (2.7 ± 0.9) x 10⁴ (n = 3). Both setups efficiently isolate cyclotron-produced ⁵¹MnCl₂ suitable for human administration as determined by developed Chemistry, Manufacturing, and Controls (CMC) acceptance criteria, and support exploration of ⁵¹Mn as a clinical diagnostic tool.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142 ","pages":"Article 108989"},"PeriodicalIF":3.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896327","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":"PET imaging of the anticancer drug candidate [11C]trimebutine in a rat glioma model","authors":"Jia-zhe Lin ,&nbsp;Maria Kominia ,&nbsp;Janine Doorduin ,&nbsp;Erik F.J. de Vries","doi":"10.1016/j.nucmedbio.2024.108985","DOIUrl":"10.1016/j.nucmedbio.2024.108985","url":null,"abstract":"<div><h3>Purpose</h3><div>Preclinical studies suggest that trimebutine could be a potential treatment for glioblastoma. The aim of this study was to investigate the distribution, kinetics and tumor accumulation of [¹¹C]trimebutine.</div></div><div><h3>Method</h3><div>A proliferation assay and cell scratch healing assay were performed to confirm the antitumor effects of trimebutine on C6 glioma cells in-vitro. Trimebutine was subsequently labeled with ¹¹C. The distribution and kinetics of [¹¹C]trimebutine in health rats and rats with an orthotopic C6 glioma were evaluated by ex-vivo gamma counting and positron emission tomography, respectively. Blocking experiments with an excess of unlabeled trimebutine or the μ-opioid receptor ligand cyprodime were employed to determine if trimebutine exhibits saturable binding in the brain. In addition, plasma stability of the tracer was assessed.</div></div><div><h3>Results</h3><div>The proliferation assay and cell scratch healing assay confirmed that trimebutine has anti-tumor effects in-vitro. [¹¹C]Trimebutine with a radiochemical purity &gt;98 % was synthesized in 15 ± 5 % radiochemical yield. In peripheral organs, the highest accumulation of the tracer was detected in excretion organs. In the brain, the highest tracer uptake was observed in the brainstem and the lowest in the hypothalamus, although differences between regions were small. PET imaging showed rapid brain uptake of [¹¹C]trimebutine, followed by a gradual washout. Administration of an intravenous dose of trimebutine (10 mg/kg) significantly decreased the uptake in all brain regions (<em>p</em> &lt; 0.05), except midbrain. Likewise, administration of cyprodime (2 mg/kg) significantly reduced [¹¹C]trimebutine uptake in the brain (<em>p</em> &lt; 0.01). However, uptake of [¹¹C]trimebutine in the tumor was not significantly different from its brain uptake in rats bearing an orthotopic C6 glioma. The percentage of intact [¹¹C]trimebutine at 60 min post injection was only 1.7 ± 0.6 %.</div></div><div><h3>Conclusion</h3><div>Trimebutine exhibits inhibitory effects on the growth and migration of glioma cells in a dose- and time-dependent manner. [¹¹C]Trimebutine was able to penetrate the blood-brain barrier in rats and tracer uptake could be significantly reduced by administration of a μ-opioid receptor antagonist. However, [¹¹C]trimebutine failed to selectively accumulate in orthotopic C6 glioma, which could be caused by low expression levels of the drug target in these tumors, or by fast metabolism of the tracer.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142 ","pages":"Article 108985"},"PeriodicalIF":3.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813842","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}