Nuclear medicine and biology最新文献

{"title":"Evaluation of astatine-211-labeled benzoate derivatives for improved in vivo stability","authors":"Mutsuho Murata ,&nbsp;Kento Kannaka ,&nbsp;Souta Tatsuta ,&nbsp;Yui Terasaka ,&nbsp;Ryota Nonaka ,&nbsp;Hiroyuki Suzuki ,&nbsp;Kazuhiro Takahashi ,&nbsp;Tomoya Uehara","doi":"10.1016/j.nucmedbio.2025.109561","DOIUrl":"10.1016/j.nucmedbio.2025.109561","url":null,"abstract":"<div><h3>Purpose</h3><div>Astatine-211 (²¹¹At) is one of the most promising α-particle-emitting radionuclides used for targeted-alpha therapy. Benzene derivatives are currently commonly used as ²¹¹At-labeling moieties for preparing ²¹¹At-labeled compounds. However, ²¹¹At-labeled compounds using benzene derivatives as the ²¹¹At-labeling moiety have known low stability against <em>in vivo</em> deastatination. We hypothesized that the deastatination of ²¹¹At-labeled benzene derivatives is enzyme-mediated, and that the inclusion of a bulky structure near the ²¹¹At-astatobenzene would stabilize it by inhibiting recognition by the enzymes.</div></div><div><h3>Methods</h3><div>In this study, we synthesized oligopeptides with D-type amino acids, such as D-glutamic acid (e), D-alanine (a), and <span>d</span>-lysine (k), which have high metabolic stability against peptidases, and bound them with ²¹¹At-astatobenzoate. Then, we evaluated the stability of these ²¹¹At-labeled compounds against deastatination <em>in vivo</em>.</div></div><div><h3>Results</h3><div>²¹¹At-labeled mono- or di-D-glutamic acid ([²¹¹At]At-Bz-e or [²¹¹At]At-Bz-ee) and ²¹¹At-labeled tri-D-alanine ([²¹¹At]At-Bz-aaa) showed high to moderate accumulation of radioactivity in the stomach and thyroid, whereas ²¹¹At-labeled tri-D-glutamic acid ([²¹¹At]At-Bz-eee) and ²¹¹At-labeled tri-<span>d</span>-lysine ([²¹¹At]At-Bz-kkk) showed low radioactivity levels in the stomach and thyroid. Furthermore, ²¹¹At-labeled tri-L-glutamic acid ([²¹¹At]At-Bz-EEE) displayed a higher accumulation in the stomach than [²¹¹At]At-Bz-eee. These results suggested that the <em>in vivo</em> deastatination of ²¹¹At-astatobenzene derivatives is not attributable to the weakness of the At<img>C bond, but rather to metabolization to smaller molecules with less steric hindrance to the ²¹¹At-labeling moiety <em>in vivo</em> and subsequent enzyme-mediated deastatination.</div></div><div><h3>Conclusions</h3><div>Our findings indicated that if ²¹¹At-labeled compounds can place the steric hindrance of the tripeptide size in the vicinity of ²¹¹At-astatobenzene, <em>in vivo</em> stable ²¹¹At-labeled compounds can be produced, even when using the ²¹¹At-astatobenzen structure as a ²¹¹At-labeling moiety.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"150 ","pages":"Article 109561"},"PeriodicalIF":3.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244812","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":"Alternative production of Lead-203: Optimizing production, purification, and radiolabelling for enhanced theranostic applications","authors":"Nadia Audouin ,&nbsp;Héloïse Dufour ,&nbsp;Aurélien Vidal ,&nbsp;Nicolas Bozovic ,&nbsp;Fabien Brelet ,&nbsp;Remy Dureau ,&nbsp;Arnaud Guertin ,&nbsp;Keerthana Kamalakannan ,&nbsp;Etienne Nigron ,&nbsp;Tony Prezeau ,&nbsp;Maryne Tarinas ,&nbsp;Katalin Briand ,&nbsp;Lou Galichet ,&nbsp;Ferid Haddad ,&nbsp;Thomas Sounalet","doi":"10.1016/j.nucmedbio.2025.109559","DOIUrl":"10.1016/j.nucmedbio.2025.109559","url":null,"abstract":"<div><h3>Introduction</h3><div>this study investigates the production of Lead-203 (²⁰³Pb) using a deuteron beam and demonstrates its application with DOTATATE for diagnostic imaging of neuroendocrine tumours (NETs) thanks to its γ-ray emissions well-suited for SPECT imaging. ²⁰³Pb presents a high potential in nuclear medicine, as it is the imaging counterpart of part of Lead-212 (²¹²Pb), a radionuclide with an alpha-emitting decay chain used for targeted alpha therapy.</div></div><div><h3>Methods</h3><div>Enriched Thallium-205 (²⁰⁵Tl) was electrodeposited onto a gold substrate using a custom-made PEEK cell, with a platinum rod as the auxiliary electrode. The electrodeposition was conducted at a controlled temperature and stirring speed, with reverse pulse potentials applied to obtain a smooth and dense deposit. The ²⁰⁵Tl deposit was then irradiated with deuteron beams at 31 MeV to produce ²⁰³Pb. Chemical separation was performed using two columns containing Pb resin. The first column (150 mg resin) was used to remove ²⁰⁵Tl for further recycling and the second column (60 mg resin) was employed to obtain ²⁰³Pb in 1 M ammonium acetate at pH 5 ensuring high purity and specific activity. Radiolabelling of DOTATATE with ²⁰³Pb was conducted in a modified acetate buffer, and the radiochemical purity and stability were assessed using HPLC and TLC. The stability of [²⁰³Pb]Pb-DOTATATE was evaluated over a period of up to 120 h.</div></div><div><h3>Results</h3><div>the electrodeposition process, conducted over 8 h, yielded a reproducible ²⁰⁵Tl deposit with an average thickness of 37.7 ± 3.2 μm, which remained stable during irradiation. The chemical separation process achieved a ²⁰³Pb purity exceeding 99 % in 1 M ammonium acetate at pH 5, with a specific activity surpassing 3783 TBq/g for an integrated beam current of 175 μAh at calibration time (EOB + 32 h). The radiochemical separation yield during the process was 80.5 %. Radiolabelling of DOTATATE with ²⁰³Pb showed a high radiochemical purity (99.1 %) and a stability over 96 h, demonstrating the feasibility of using [²⁰³Pb]Pb-DOTATATE for clinical applications.</div></div><div><h3>Conclusion</h3><div>Our results support the use of ²⁰³Pb produced using deuteron beam as valuable tools in the advancement of personalized nuclear medicine therapies. The high purity and specific activity of ²⁰³Pb, achieved through dual Pb resin purification process, along with its effective radiolabelling with DOTATATE at high yield and long stability, underscore its potential for clinical use in diagnostic imaging, especially in neuroendocrine tumours.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"150 ","pages":"Article 109559"},"PeriodicalIF":3.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155922","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]FDG-PET provides insights into the liver-brain axis and confirms SUVgluc as a surrogate for MRGlu in a mouse model of liver fibrosis","authors":"Thomas Wanek ,&nbsp;Mari Teuter ,&nbsp;Asha Balakrishnan ,&nbsp;Tobias L. Ross ,&nbsp;Frank M. Bengel ,&nbsp;Michael Ott ,&nbsp;Marion Bankstahl ,&nbsp;Jens P. Bankstahl","doi":"10.1016/j.nucmedbio.2025.109095","DOIUrl":"10.1016/j.nucmedbio.2025.109095","url":null,"abstract":"<div><h3>Purpose</h3><div>The liver-brain axis regulates metabolic homeostasis, with glucose metabolism playing a key role. Liver dysfunction, such as fibrosis, may impact brain metabolism and consequently, brain function. Positron emission tomography (PET) imaging provides a non-invasive approach to study glucose metabolism in both organs. A recent longitudinal PET/CT study utilizing 2-deoxy-2-[¹⁸F]-fluoro-<span>d</span>-glucose ([¹⁸F]FDG) amongst other radiotracers revealed significant metabolic changes in the liver in a mouse model of liver fibrosis. Here, we retrospectively analyzed those data to quantify potential associated changes in brain glucose metabolism.</div></div><div><h3>Procedures</h3><div>Eleven male C57BL/6N mice underwent repeated PET imaging with [¹⁸F]FDG at baseline, pre-fibrosis, fibrosis, and remission stages. Cerebral glucose metabolism was assessed using standardized uptake value (<em>SUV</em>), blood glucose-corrected <em>SUV</em> (<em>SUV</em>_{<em>gluc</em>}), and kinetic modeling (Patlak and two-tissue compartment models) for calculation of the glucose metabolic rate (<em>MR</em>_<em>Glu</em>).</div></div><div><h3>Results</h3><div>Both <em>SUV</em>_{<em>gluc</em>} and <em>MR</em>_<em>Glu</em> significantly decreased during pre-fibrosis and fibrosis on whole brain level and recovered at remission. <em>SUV</em>_{<em>gluc</em>} statistical parametric mapping identified multiple brain areas with reduced glucose metabolism, which was confirmed by regional analysis showing progressive reduction in SUV_gluc. Correlation analyses confirmed <em>SUV</em>_{<em>gluc</em>} as a reliable surrogate for <em>MR</em>_<em>Glu</em>, unlike uncorrected <em>SUV</em>. Liver [¹⁸F]FDG uptake increased during fibrosis and normalized at remission, mirroring changes in blood glucose concentrations.</div></div><div><h3>Conclusions</h3><div>[¹⁸F]FDG PET imaging revealed that liver fibrosis alters glucose metabolism in both liver and brain, emphasizing the potential of molecular imaging for future assessment of metabolic interaction between liver and brain. [¹⁸F]FDG uptake in terms of <em>SUV</em>_{<em>gluc</em>} strongly correlated with <em>MR</em>_<em>Glu</em> from kinetic modeling, supporting its utility as a valid surrogate parameter to quantify cerebral glucose metabolism in mice.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"150 ","pages":"Article 109095"},"PeriodicalIF":3.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997488","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 radiotracer targeting the complement C3a receptor","authors":"Ravi Naik ,&nbsp;Hyojin Cha ,&nbsp;Fangyi Shen ,&nbsp;Deepankar Das ,&nbsp;Andrew Hall ,&nbsp;Daniel Holt ,&nbsp;William B. Mathews ,&nbsp;Robert F. Dannals ,&nbsp;Il Minn ,&nbsp;Mikhail Pletnikov ,&nbsp;Martin G. Pomper ,&nbsp;Andrew G. Horti","doi":"10.1016/j.nucmedbio.2025.109093","DOIUrl":"10.1016/j.nucmedbio.2025.109093","url":null,"abstract":"<div><h3>Background</h3><div>Positron-emission tomography (PET) imaging of the complement system could advance understanding of the innate immune system in central nervous system (CNS) diseases and development of new drugs. The goal of this study was to develop a PET radiotracer targeting the C3a receptor (C3aR) of the complement system.</div></div><div><h3>Methods</h3><div>C3aR radiotracer [¹⁸F]<strong>1</strong> was synthesized in one step. Imaging properties of the radiotracer in the brain were tested in ex vivo experiments in mice.</div></div><div><h3>Results</h3><div>[¹⁸F]<strong>1</strong> was radiolabeled with radiochemical yield of 4 %, radiochemical purity &gt;95 % and molar activity ~155 GBq/μmol. In control mice [¹⁸F]<strong>1</strong> demonstrated high brain uptake (9 %ID/g tissue) which gradually increased over the 90 min of the study period and represented mainly non-specific binding. The C3aR specificity (18 %) of [¹⁸F]<strong>1</strong> binding in the brain of control mice was determined in a blocking experiment. The brain uptake of [¹⁸F]<strong>1</strong> was significantly increased (~2 – fold) in a murine model of neuroinflammation [lipopolysaccharide (LPS) – treated mice]. The blocking experiments in LPS-treated mice showed a dose-dependent reduction in whole-brain uptake of [¹⁸F]<strong>1</strong> demonstrating that the blocked binding is partially specific (43 %) and dependent upon C3aR. This study demonstrated the feasibility of development a PET radiotracer for specific imaging of C3aR in neuroinflammation. However, [¹⁸F]<strong>1</strong> is suboptimal for further studies, because of its insufficient specific binding in neuroinflammation model, high non-specific binding and slow irreversible kinetics in the mouse brain. Future research should focus on developing of optimized C3aR PET tracers with improved specific binding, reduced non-specific binding, reversible pharmacokinetics and, also, better radiochemistry.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"150 ","pages":"Article 109093"},"PeriodicalIF":3.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027300","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":"NMB Innovators Series Professor Heinz Hubert Coenen, PhD","authors":"Johannes Ermert ,&nbsp;Stephen Moerlein","doi":"10.1016/j.nucmedbio.2025.109094","DOIUrl":"10.1016/j.nucmedbio.2025.109094","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"148 ","pages":"Article 109094"},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109108","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":"L-5-[11C]-glutamine PET of breast cancer: Preclinical studies in mouse models","authors":"Christopher T. Hensley ,&nbsp;Prashanth Padakanti ,&nbsp;Raheema Damani ,&nbsp;Christina Dulal ,&nbsp;Hoon Choi ,&nbsp;Shihong Li ,&nbsp;Jianbo Cao ,&nbsp;Hsiaoju Lee ,&nbsp;Austin Pantel ,&nbsp;Elizabeth Li ,&nbsp;David Mankoff ,&nbsp;Rong Zhou","doi":"10.1016/j.nucmedbio.2025.109092","DOIUrl":"10.1016/j.nucmedbio.2025.109092","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Glutamine is an important metabolic substrate in many aggressive tumors, with comparable importance to glucose metabolism. Utilizing human breast cancer mouse xenograft models, we studied the kinetics of the PET imaging agent, &lt;em&gt;L&lt;/em&gt;-5-[&lt;sup&gt;11&lt;/sup&gt;C]-glutamine ([&lt;sup&gt;11&lt;/sup&gt;C]glutamine or [&lt;sup&gt;11&lt;/sup&gt;C]GLN) a biochemical authentic substrate for glutamine metabolism, to further characterize the metabolism of glutamine and downstream labeled metabolites. Studies were performed with and without inhibition of the enzyme, glutaminase (GLS), the first step in glutamine catabolism that generates glutamate, and key target for therapy directed to glutamine-metabolizing cancers.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The study used xenograft mouse models for two breast cancer cell lines, HCC1806, a highly glutaminolytic triple-negative cell line, and MCF-7, a hormone receptor positive line with only low levels of glutaminolysis. Mice were injected with [&lt;sup&gt;11&lt;/sup&gt;C]glutamine and either underwent metabolite analysis or dynamic PET imaging. The contributions of individual metabolites to the total &lt;sup&gt;11&lt;/sup&gt;C-activity signal in blood and tumor tissue were measured at 10, 20, and 30 min &lt;em&gt;via&lt;/em&gt; HPLC. We measured fractional activity in the form of [&lt;sup&gt;11&lt;/sup&gt;C]glutamine &lt;em&gt;versus&lt;/em&gt; labeled metabolites, focusing on &lt;em&gt;L&lt;/em&gt;-5-[&lt;sup&gt;11&lt;/sup&gt;C]-glutamate ([&lt;sup&gt;11&lt;/sup&gt;C]glutamate or [&lt;sup&gt;11&lt;/sup&gt;C]GLU), and any activity in the other metabolite small molecules labeled with &lt;sup&gt;11&lt;/sup&gt;C (&lt;sup&gt;11&lt;/sup&gt;C-other or &lt;sup&gt;11&lt;/sup&gt;C-OTH). Additionally, the contribution of [&lt;sup&gt;11&lt;/sup&gt;C]CO&lt;sub&gt;2&lt;/sub&gt; to total &lt;sup&gt;11&lt;/sup&gt;C-activity was measured. Together with image-based uptake curves, this generated estimated time activity curves for [&lt;sup&gt;11&lt;/sup&gt;C]glutamine and downstream metabolites in both xenograft models treated with vehicle or GLS inhibitor (CB-839).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We found that, out to 30 min post-injection, the majority of radioactivity in highly glutaminolytic tumors (HCC1806) was in the form of [&lt;sup&gt;11&lt;/sup&gt;C]glutamine and [&lt;sup&gt;11&lt;/sup&gt;C]glutamate, with relatively low amounts of radioactivity in metabolites downstream of glutamate including [&lt;sup&gt;11&lt;/sup&gt;C]CO&lt;sub&gt;2&lt;/sub&gt;. In HCC1806 tumors, [&lt;sup&gt;11&lt;/sup&gt;C]glutamate was retained in the large cellular glutamate pool leading to a majority fraction of total radioactivity in tumor tissue that is greater than the fraction within the blood, with this tumoral fractional pattern reversing with CB-839. This phenomenon leads to a total tumor time-activity curve that is only marginally different before and after CB-839. The radioactivity patterns of MCF-7 tumors after vehicle treatment were similar HCC1806 tumors after CB-839 treatment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Our studies on [&lt;sup&gt;11&lt;/sup&gt;C]glutamine in breast cancer models show significant retention of &lt;sup&gt;11&lt;/sup&gt;C-activity in the form of [&lt;sup&gt;11&lt;/sup&gt;C]glutamate in ","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"150 ","pages":"Article 109092"},"PeriodicalIF":3.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011171","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":"Imaging and targeting S1PR1 in HER2+ tumors","authors":"Shayla Shmuel ,&nbsp;Lin Qiu ,&nbsp;Alex Vanover ,&nbsp;Hong Chen ,&nbsp;Hao Jiang ,&nbsp;Zhude Tu ,&nbsp;Patrícia M.R. Pereira","doi":"10.1016/j.nucmedbio.2025.109057","DOIUrl":"10.1016/j.nucmedbio.2025.109057","url":null,"abstract":"<div><div>Human Epidermal Growth Factor Receptor 2 (HER2) is a membrane receptor tyrosine kinase overexpressed in a subset of gastric cancers and is the target of multiple clinically approved therapies, including the antibody-drug conjugate trastuzumab deruxtecan (T-DXd). However, resistance to HER2-directed therapies remains a major challenge in gastric cancer. Sphingosine-1-phosphate receptor 1 (S1PR1), a G-protein-coupled receptor involved in oncogenic signaling, has been associated with poor prognosis and therapy resistance. This study investigated the role of S1PR1 in modulating response to HER2-targeted therapy and explored therapeutic dual targeting of HER2 and S1PR1. We used immunohistochemistry, Western blot analyses, and S1PR1-targeted radiotracer to assess S1PR1 expression in patient-derived xenograft samples and preclinical tumor models. We observed decreased S1PR1 in tumors that responded to T-DXd and trastuzumab therapy. In contrast, tumors with persistent S1PR1 expression exhibited resistance to HER2-targeted therapy. The S1PR1 inhibitor fingolimod, when combined with T-DXd, significantly enhanced therapeutic efficacy in HER2+/S1PR1+ tumors, resulting in reduced HER2 and S1PR1 protein levels and decreased tumor volume. This work demonstrates that S1PR1 expression is associated with resistance to HER2-targeted therapy, and S1PR1 PET has potential as a biomarker for selecting patients for HER2-targeted therapy, and S1PR1 has the potential to monitor T-DXd therapeutic response.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"148 ","pages":"Article 109057"},"PeriodicalIF":3.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829899","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":"Characterization of [¹¹C]DASB and [¹⁸F]FE-PE2I using microPET imaging in SERT and DAT knockout rats.","authors":"Cyprien G J Guerrin, Debbie R M Tesselaar, Emile E Zweistra, Anna Cabiscol-Claveria, Bieneke Janssen, Janine Doorduin, Arnt F A Schellekens, Jan Booij, Judith R Homberg","doi":"10.1016/j.nucmedbio.2025.109055","DOIUrl":"https://doi.org/10.1016/j.nucmedbio.2025.109055","url":null,"abstract":"<p><strong>Rationale: </strong>[¹¹C]DASB is widely used for PET imaging of brain serotonin transporters (SERT) and the tropane ligand [¹⁸F]FE-PE2I is used for PET imaging of dopamine transporters (DAT). However, their in vivo selectivity has not been confirmed using knockout (KO) models. This study aimed to provide direct in vivo evidence for the selectivity of these tracers using SERT and DAT KO rats.</p><p><strong>Methods: </strong>High-resolution microPET imaging was performed in male SERT KO, DAT KO, and wild-type (WT) rats. Animals were dynamically scanned either for 60 min with [¹¹C]DASB for SERT, or for 45 min with [¹⁸F]FE-PE2I for DAT. Binding potential (BP_ND) was estimated using the simplified reference tissue model with the cerebellum as reference. Whole-brain regions were analyzed for [¹¹C]DASB, and striatal regions for [¹⁸F]FE-PE2I using descriptive and effect size metrics.</p><p><strong>Results: </strong>Specific tracer binding was visually absent in KO animals across all target regions. Quantitatively, [¹⁸F]FE-PE2I BPND in DAT KO rats was reduced by 94.2 % in the whole striatum, and [¹¹C]DASB BPND in SERT KO rats was reduced by a mean of 89.3 % across cortical, subcortical, and brainstem regions. These reductions were associated with larger effect sizes (Cohen's d ≥ 2.8).</p><p><strong>Conclusion: </strong>This study provides in vivo characterization of [¹¹C]DASB and [¹⁸F]FE-PE2I selectivity and highlights the utility of genetic models for PET tracer evaluation.</p>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"148-149 ","pages":"109055"},"PeriodicalIF":3.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804394","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":"Predictive tumor dosimetry and pharmacokinetic evaluation of [67Cu]Cu-rhPSMA-10.1 and [68Ga]Ga-rhPSMA-10.1 with PET/SPECT MRI in an orthotopic mouse model of glioblastoma","authors":"Thomas Kolle Ekaney ,&nbsp;Ursula Søndergaard ,&nbsp;Rodrigo Berzaghi ,&nbsp;Stine Figenschau ,&nbsp;Rune Sundset ,&nbsp;Angel Moldes-Anaya ,&nbsp;Mathias Kranz","doi":"10.1016/j.nucmedbio.2025.109056","DOIUrl":"10.1016/j.nucmedbio.2025.109056","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Targeted radionuclide therapy (TRT) is an emerging pillar of precision medicine, with prostate-specific membrane antigen (PSMA)-targeted agents like [&lt;sup&gt;177&lt;/sup&gt;Lu]PSMA-617 demonstrating notable clinical success. Achieving optimal therapeutic efficacy while minimizing toxicity requires precise tumor and organ dosimetry based on accurate time-activity curves (TACs) derived from molecular imaging. Glioblastoma (GBM), a highly treatment-resistant brain tumor with limited therapeutic possibilities, has shown PSMA expression, opening new avenues for TRT. Copper-67, a promising theranostic isotope producible in standard hospital-based cyclotrons, offers previously unavailable opportunities for such applications. In this study, we evaluated the feasibility of [&lt;sup&gt;67&lt;/sup&gt;Cu]Cu-rhPSMA-10.1 for TRT analyzed by SPECT and [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-rhPSMA-10.1 for PET-based imaging and predictive dosimetry in an orthotopic GBM mouse model.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;&lt;sup&gt;67&lt;/sup&gt;Cu was produced &lt;em&gt;via&lt;/em&gt; a biomedical cyclotron, purified, and validated using gamma spectrometry and ICP-OES. [&lt;sup&gt;67&lt;/sup&gt;Cu]Cu-rhPSMA-10.1 and [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-rhPSMA-10.1 were synthesized with high radiochemical purity. GL261-luc2 GBM tumors were implanted in eight C57BL/6JRj mice. One hour PET and up to 72 h SPECT imaging were performed. PET pharmacokinetic modeling analyzed tumor uptake and whole-body biodistribution. &lt;em&gt;Ex vivo&lt;/em&gt; gamma counting was applied to validate image-derived organ distribution. Tumor dosimetry was estimated using PET-derived TAC and validated by SPECT, with absorbed dose calculations performed &lt;em&gt;via&lt;/em&gt; sphere- and voxel-based models (IDAC-dose 2.1 or Imalytics). Whole-body dosimetry was assessed using OLINDA 2.0. Immunohistochemical (IHC) staining against PSMA and CD31 was performed in human GBM tissue to validate the imaging findings.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;PET confirmed significantly higher tumor uptake of [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-rhPSMA-10.1 compared to healthy brain (SUVR 1.9 ± 0.5, 60 min). Pharmacokinetic modeling identified elevated tumor perfusion (K1 = 0.3 ± 0.07 mL/cm&lt;sup&gt;3&lt;/sup&gt;/min) and volume of distribution (Vt = 0.26 ± 0.05 mL/cm&lt;sup&gt;3&lt;/sup&gt;) relative to healthy brain. Predictive tumor dosimetry using [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-rhPSMA-10.1 PET data extrapolated to [&lt;sup&gt;67&lt;/sup&gt;Cu]Cu-rhPSMA-10.1 estimated a mean tumor dose of up to 31.1 mGy/MBq. Multi-time-point SPECT imaging confirmed tumor uptake of [&lt;sup&gt;67&lt;/sup&gt;Cu]Cu-rhPSMA-10.1, with an absorbed tumor dose of 29.1 mGy/MBq, resembling closely the predicted value. IHC staining confirmed expression of PSMA in human GBM tissue and its localization in vasculature.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This study demonstrates the translational potential of [&lt;sup&gt;67&lt;/sup&gt;Cu]Cu-rhPSMA-10.1 as a targeted radionuclide therapy for PSMA-expressing GBM, supported by predictive PET-based dosimetry using [&lt;sup&gt;68&lt;/sup&gt;Ga]Ga-rhPSMA-10.1. Tumor dose estimates d","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"148 ","pages":"Article 109056"},"PeriodicalIF":3.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144770784","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 cannabinoid receptor 2 ligand 4-O-[11C]methylhonokiol 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.2025.109054","DOIUrl":"10.1016/j.nucmedbio.2025.109054","url":null,"abstract":"<div><h3>Purpose</h3><div>Several studies have suggested that the neolignan 4-<em>O</em>-methylhonokiol has antitumor activity. The aim of this study was to investigate the distribution, kinetics and tumor accumulation of this potential antitumor agent.</div></div><div><h3>Methods</h3><div>4-<em>O</em>-methylhonokiol was labeled with ¹¹C. To identifying the target receptors of 4-O-[¹¹C]methylhonokiol, receptor blocking experiments were performed on C6 glioma cells. The distribution and kinetics in health rats and rats with an orthotopic C6 glioma were evaluated by positron emission tomography (PET) and ex-vivo gamma counting.</div></div><div><h3>Results</h3><div>4-O-[¹¹C]methylhonokiol with a radiochemical purity 96.8 ± 1.8 % was synthesized in 3.4 ± 1.3 % non-decay corrected radiochemical yield. In-vitro receptor blocking experiments showed that 4-O-[¹¹C]methylhonokiol binds specifically to the cannabinoid receptor 2 (CB2R). PET showed rapid brain uptake of 4-O-[¹¹C]methylhonokiol, followed by a gradual washout. Administration of 4-<em>O</em>-methylhonokiol (20 mg/kg i.v.) prior to tracer injection caused a significant increase in 4-O-[¹¹C]methylhonokiol brain uptake (<em>p</em> &lt; 0.05). Such an increase in brain uptake was also observed in rats treated with the P-glycoprotein (P-gp) inhibitor tariquidar. Administration of the CBR2 antagonist AM630 before tracer injection in C6 glioma-bearing rats resulted in a significant reduction in 4-O-[¹¹C]methylhonokiol uptake in the brain and the tumor. Tumor uptake of 4-O-[¹¹C]methylhonokiol was not significantly different from its brain uptake in both AM630-treated and control rats.</div></div><div><h3>Conclusion</h3><div>These results indicate that 4-O-[¹¹C]methylhonokiol binds specifically to CB2 receptors in the brain and tumor in glioma-bearing rats. However, our results suggest that 4-O-[¹¹C]methylhonokiol is also a substrate of P-gp in the blood-brain barrier and C6 glioma. 4-O-[¹¹C]methylhonokiol may therefore be further evaluated as a tracer for P-gp.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"148 ","pages":"Article 109054"},"PeriodicalIF":3.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780934","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}