Pub Date : 2025-03-29DOI: 10.1016/j.nucmedbio.2025.109011
Benjamin B. Tournier , Zahra Mansouri , Yazdan Salimi , Kelly Ceyzériat , Gregory Mathoux , Hélène Richard-Lepouriel , Daniel Zullino , Frédéric Bois , Habib Zaidi , Valentina Garibotto , Stergios Tsartsalis , Philippe Millet
Purpose
The 18 kDa translocator protein (TSPO) is a mitochondrial protein that becomes overexpressed during neuroinflammatory conditions, such as in Alzheimer's disease or multiple sclerosis. TSPO is of interest because it serves as a marker for microglial and astrocytic activity, measurable via in vivo positron emission tomography (PET) molecular imaging. [18F]PBR111 is a second-generation TSPO PET radioligand with high signal specificity but a sensitivity to TSPO polymorphism, in comparison with first-generation ligands. This study focused on the biodistribution and dosimetry of [18F]PBR111 in healthy humans.
Method
Six volunteers (three males, three females) were administered approximately 200 MBq of [18F]PBR111. Organs such as the lungs and liver showed the highest initial radioactivity level, while the bone marrow and bladder accumulated activity over time, likely reflecting ligand defluorination and elimination.
Results
Dosimetry findings revealed a total effective dose of 16.17 μSv/MBq, equivalent to 3.04 mSv per examination. Compared to animal models, human dosimetry showed lower radiation exposure, highlighting discrepancies in predictive models. Organ-specific dose comparisons with other TSPO ligands ([18F]PBR06, [18F]FEPPA, [18F]FEDAA1106) revealed similar distribution patterns. This study underscores the clinical viability of [18F]PBR111 for TSPO imaging, providing critical data for optimizing its safe use in research and clinical settings.
Conclusion
The findings support its potential for studying neuroinflammatory and systemic diseases. The trial registration number is NCT06398392.
{"title":"Radiation dosimetry of the 18 kDa translocator protein ligand [18F]PBR111 in humans","authors":"Benjamin B. Tournier , Zahra Mansouri , Yazdan Salimi , Kelly Ceyzériat , Gregory Mathoux , Hélène Richard-Lepouriel , Daniel Zullino , Frédéric Bois , Habib Zaidi , Valentina Garibotto , Stergios Tsartsalis , Philippe Millet","doi":"10.1016/j.nucmedbio.2025.109011","DOIUrl":"10.1016/j.nucmedbio.2025.109011","url":null,"abstract":"<div><h3>Purpose</h3><div>The 18 kDa translocator protein (TSPO) is a mitochondrial protein that becomes overexpressed during neuroinflammatory conditions, such as in Alzheimer's disease or multiple sclerosis. TSPO is of interest because it serves as a marker for microglial and astrocytic activity, measurable via in vivo positron emission tomography (PET) molecular imaging. [<sup>18</sup>F]PBR111 is a second-generation TSPO PET radioligand with high signal specificity but a sensitivity to TSPO polymorphism, in comparison with first-generation ligands. This study focused on the biodistribution and dosimetry of [<sup>18</sup>F]PBR111 in healthy humans.</div></div><div><h3>Method</h3><div>Six volunteers (three males, three females) were administered approximately 200 MBq of [<sup>18</sup>F]PBR111. Organs such as the lungs and liver showed the highest initial radioactivity level, while the bone marrow and bladder accumulated activity over time, likely reflecting ligand defluorination and elimination.</div></div><div><h3>Results</h3><div>Dosimetry findings revealed a total effective dose of 16.17 μSv/MBq, equivalent to 3.04 mSv per examination. Compared to animal models, human dosimetry showed lower radiation exposure, highlighting discrepancies in predictive models. Organ-specific dose comparisons with other TSPO ligands ([<sup>18</sup>F]PBR06, [<sup>18</sup>F]FEPPA, [<sup>18</sup>F]FEDAA1106) revealed similar distribution patterns. This study underscores the clinical viability of [<sup>18</sup>F]PBR111 for TSPO imaging, providing critical data for optimizing its safe use in research and clinical settings.</div></div><div><h3>Conclusion</h3><div>The findings support its potential for studying neuroinflammatory and systemic diseases. The trial registration number is <span><span>NCT06398392</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 109011"},"PeriodicalIF":3.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747246","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}
Pub Date : 2025-03-03DOI: 10.1016/j.nucmedbio.2025.109008
A.R. Jalilian , J. Kleynhans , P. Bouziotis , F. Bruchertseifer , S. Chakraborty , E. De Blois , M. Denecke , U. Elboga , M. Gizawy , C. Horak , J. Jang , A. Korde , A. Majkowska-Pilip , A. Mdlophane , B. Ocampo-Garcia , S.V. Selivanova , V. Starovoitova , W. Wojdowska , J.R. Zeevaart , V. Radchenko
Due to the growing interest of International Atomic Energy Agency (IAEA) Member States in implementing targeted radionuclide therapy (TRT) in general, the demand for alpha-emitting radionuclides and radiopharmaceuticals is enormous. As an international platform for peaceful applications of radionuclides, the IAEA has been implementing several activities focusing on the production and quality control of alpha emitters and radiopharmaceuticals as well as capacity building in the field, through Technical Meetings, Workshops, Publications and Conference Supports, IAEA-Coordinated Research Projects (CRP) and Technical Cooperation Program (TC). This review article summarises the IAEA activities on the production and quality control of alpha emitter radiopharmaceuticals for targeted alpha therapy (TAT) and a roadmap to future steps including but not limited to the ongoing CRP on 225Ac-radiopharmaceuticals.
{"title":"IAEA activities to support the member states in the production of targeted alpha therapy radiopharmaceuticals","authors":"A.R. Jalilian , J. Kleynhans , P. Bouziotis , F. Bruchertseifer , S. Chakraborty , E. De Blois , M. Denecke , U. Elboga , M. Gizawy , C. Horak , J. Jang , A. Korde , A. Majkowska-Pilip , A. Mdlophane , B. Ocampo-Garcia , S.V. Selivanova , V. Starovoitova , W. Wojdowska , J.R. Zeevaart , V. Radchenko","doi":"10.1016/j.nucmedbio.2025.109008","DOIUrl":"10.1016/j.nucmedbio.2025.109008","url":null,"abstract":"<div><div>Due to the growing interest of International Atomic Energy Agency (IAEA) Member States in implementing targeted radionuclide therapy (TRT) in general, the demand for alpha-emitting radionuclides and radiopharmaceuticals is enormous. As an international platform for peaceful applications of radionuclides, the IAEA has been implementing several activities focusing on the production and quality control of alpha emitters and radiopharmaceuticals as well as capacity building in the field, through Technical Meetings, Workshops, Publications and Conference Supports, IAEA-Coordinated Research Projects (CRP) and Technical Cooperation Program (TC). This review article summarises the IAEA activities on the production and quality control of alpha emitter radiopharmaceuticals for targeted alpha therapy (TAT) and a roadmap to future steps including but not limited to the ongoing CRP on <sup>225</sup>Ac-radiopharmaceuticals.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 109008"},"PeriodicalIF":3.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594094","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}
Pub Date : 2025-03-01DOI: 10.1016/j.nucmedbio.2025.109009
Marianna Tosato , Chiara Favaretto , Janke Kleynhans , Andrew R. Burgoyne , Jean-François Gestin , Nicholas P. van der Meulen , Amirreza Jalilian , Ulli Köster , Mattia Asti , Valery Radchenko
{"title":"Corrigendum to “Alpha Atlas: Mapping global production of α-emitting radionuclides for targeted alpha therapy” [Nucl Med Biol (March–April 2025) 108990]","authors":"Marianna Tosato , Chiara Favaretto , Janke Kleynhans , Andrew R. Burgoyne , Jean-François Gestin , Nicholas P. van der Meulen , Amirreza Jalilian , Ulli Köster , Mattia Asti , Valery Radchenko","doi":"10.1016/j.nucmedbio.2025.109009","DOIUrl":"10.1016/j.nucmedbio.2025.109009","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142 ","pages":"Article 109009"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636718","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}
Pub Date : 2025-02-16DOI: 10.1016/j.nucmedbio.2025.109000
Mari Teuter , Yuhai Hu , Tobias L. Ross , Kelsey Lolatte , Michael Ott , Frank M. Bengel , Asha Balakrishnan , Jens P. Bankstahl
Background
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, globally. There is a need for novel biomarkers for early detection and novel, effective targeted therapies. Molecular imaging can faithfully visualize, characterize and quantify specific relevant biological processes.
Basic procedure
We performed longitudinal dedicated small-animal positron emission tomography–computed tomography (PET/CT) imaging to analyze changes in glucose metabolism using [18F]fluorodeoxyglucose ([18F]FDG), amino acid turnover with [18F]fluoroethyltyrosine ([18F]FET), and chemokine receptor expression using [68Ga]pentixafor targeting CXCR4, during stages of early tumor development, overt HCC and regression. We used two conditional transgenic mouse models of HCC, driven by clinically relevant oncogenes c-MYC (LT2/MYC) or HRASV12 (LT2/RAS). Conditional doxycycline-regulated mouse models, enable liver-specific oncogene activation or inhibition, leading to liver tumor development and regression, respectively. Correlation of our PET/CT findings with our gene expression and metabolomics data and with histological analyses followed.
Main findings
We show PET/CT identifies HCC stage-specific and oncogene-specific molecular changes that may serve as potential novel biomarkers and therapeutic targets. Glucose metabolism and CXCR4 chemokine expression are differentially deregulated during HCC development in an oncogene-specific manner. Our [18F]FDG results correlated with glucose transporter GLUT1 gene expression and with our metabolomics data. Increased expression of CXCR4 and CD68 inflammatory markers mirrored [68Ga]pentixafor results in LT2/MYC mice. FET-based measurement of amino acid turnover are insensitive to stages of HCC-development, in our studies. Concurrently, no significant changes in expression of tyrosine metabolism genes were observed.
Principal conclusions
Our study highlights that identified changes in targeted molecular imaging can facilitate a better understanding of underlying biological processes and may help guide novel oncogene-specific targeted anti-tumor therapies in HCC, with promising translational potential.
{"title":"Longitudinal multi-tracer imaging of hepatocellular carcinoma identifies novel stage- and oncogene-specific changes","authors":"Mari Teuter , Yuhai Hu , Tobias L. Ross , Kelsey Lolatte , Michael Ott , Frank M. Bengel , Asha Balakrishnan , Jens P. Bankstahl","doi":"10.1016/j.nucmedbio.2025.109000","DOIUrl":"10.1016/j.nucmedbio.2025.109000","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, globally. There is a need for novel biomarkers for early detection and novel, effective targeted therapies. Molecular imaging can faithfully visualize, characterize and quantify specific relevant biological processes.</div></div><div><h3>Basic procedure</h3><div>We performed longitudinal dedicated small-animal positron emission tomography–computed tomography (PET/CT) imaging to analyze changes in glucose metabolism using [<sup>18</sup>F]fluorodeoxyglucose ([<sup>18</sup>F]FDG), amino acid turnover with [<sup>18</sup>F]fluoroethyltyrosine ([<sup>18</sup>F]FET), and chemokine receptor expression using [<sup>68</sup>Ga]pentixafor targeting CXCR4, during stages of early tumor development, overt HCC and regression. We used two conditional transgenic mouse models of HCC, driven by clinically relevant oncogenes c-MYC (LT2/MYC) or HRASV12 (LT2/RAS). Conditional doxycycline-regulated mouse models, enable liver-specific oncogene activation or inhibition, leading to liver tumor development and regression, respectively. Correlation of our PET/CT findings with our gene expression and metabolomics data and with histological analyses followed.</div></div><div><h3>Main findings</h3><div>We show PET/CT identifies HCC stage-specific and oncogene-specific molecular changes that may serve as potential novel biomarkers and therapeutic targets. Glucose metabolism and CXCR4 chemokine expression are differentially deregulated during HCC development in an oncogene-specific manner. Our [<sup>18</sup>F]FDG results correlated with glucose transporter GLUT1 gene expression and with our metabolomics data. Increased expression of CXCR4 and CD68 inflammatory markers mirrored [<sup>68</sup>Ga]pentixafor results in LT2/MYC mice. FET-based measurement of amino acid turnover are insensitive to stages of HCC-development, in our studies. Concurrently, no significant changes in expression of tyrosine metabolism genes were observed.</div></div><div><h3>Principal conclusions</h3><div>Our study highlights that identified changes in targeted molecular imaging can facilitate a better understanding of underlying biological processes and may help guide novel oncogene-specific targeted anti-tumor therapies in HCC, with promising translational potential.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 109000"},"PeriodicalIF":3.6,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436480","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}
Preclinical pharmacokinetic studies of therapeutic antibodies in non-human primates are desired because of the difficulty in extrapolating ADME data from animal models to humans. We evaluated the pharmacokinetics of 89Zr (Zirconium-89) -labelled anti-KLH human IgG and its metabolites to confirm their non-specific/physiological accumulation in healthy cynomolgus macaques. The anti-KLH antibody was used as a negative control, ensuring that the observed distribution reflected general IgG behavior rather than antigen-specific accumulation. This provides a valuable reference for comparing the biodistribution of targeted antibodies.
Methods
Selected IgG was conjugated to desferrioxamine (DFO), labelled with 89Zr, and injected into healthy cynomolgus macaques. PET/CT images at the whole-body level were acquired at different time points, and standard uptake values (SUV) in regions of interest, such as the heart, liver, spleen, kidneys, bone, and muscles, were calculated. The distribution of a shortened antibody variant, 89Zr-labelled Fab, as well as that of [89Zr]Zr-DFO and [89Zr]Zr-oxalate, the expected metabolites of 89Zr- labelled IgG, was also assessed.
Results
After 89Zr-labelled IgG injection, the SUV in the heart, vertebral body, and muscle decreased, in line with the 89Zr concentration decrease in the circulation, whereas radioactivity increased over time in the kidneys and liver. Autoradiography of the renal sections indicated that most of the 89Zr- labelled IgG radioactivity accumulated in the renal cortex. Relatively high accumulation in the kidneys was also observed in 89Zr- labelled Fab-injected macaques, and renal autoradiographs of these animals showed that the renal cortex was the preferred accumulation site. However, [89Zr]Zr-DFO was rapidly excreted into the urine, whereas [89Zr]Zr-oxalate was highly accumulated in the epiphysis of the long bones and vertebral body.
Conclusion
In the non-human primate cynomolgus macaque, 89Zr- labelled IgG accumulated in the kidneys and the liver. However, [89Zr]Zr-DFO and 89Zr did not accumulate in these organs. This preclinical pharmacokinetic study performed with human IgG in a non-human primate model using PET is of great significance as it sheds light on the basic fate and distribution of 89Zr- labelled IgG.
{"title":"Investigating the fate of Zirconium-89 labelled antibody in cynomolgus macaques","authors":"Takanori Sasaki , Sadaaki Kimura , Akihiro Noda , Yoshihiro Murakami , Sosuke Miyoshi , Masaru Akehi , Kazuhiko Ochiai , Masami Watanabe , Takahiro Higuchi , Eiji Matsuura","doi":"10.1016/j.nucmedbio.2025.109001","DOIUrl":"10.1016/j.nucmedbio.2025.109001","url":null,"abstract":"<div><h3>Background</h3><div>Preclinical pharmacokinetic studies of therapeutic antibodies in non-human primates are desired because of the difficulty in extrapolating ADME data from animal models to humans. We evaluated the pharmacokinetics of <sup>89</sup>Zr (Zirconium-89) -labelled anti-KLH human IgG and its metabolites to confirm their non-specific/physiological accumulation in healthy cynomolgus macaques. The anti-KLH antibody was used as a negative control, ensuring that the observed distribution reflected general IgG behavior rather than antigen-specific accumulation. This provides a valuable reference for comparing the biodistribution of targeted antibodies.</div></div><div><h3>Methods</h3><div>Selected IgG was conjugated to desferrioxamine (DFO), labelled with <sup>89</sup>Zr, and injected into healthy cynomolgus macaques. PET/CT images at the whole-body level were acquired at different time points, and standard uptake values (SUV) in regions of interest, such as the heart, liver, spleen, kidneys, bone, and muscles, were calculated. The distribution of a shortened antibody variant, <sup>89</sup>Zr-labelled Fab, as well as that of [<sup>89</sup>Zr]Zr-DFO and [<sup>89</sup>Zr]Zr-oxalate, the expected metabolites of <sup>89</sup>Zr- labelled IgG, was also assessed.</div></div><div><h3>Results</h3><div>After <sup>89</sup>Zr-labelled IgG injection, the SUV in the heart, vertebral body, and muscle decreased, in line with the <sup>89</sup>Zr concentration decrease in the circulation, whereas radioactivity increased over time in the kidneys and liver. Autoradiography of the renal sections indicated that most of the <sup>89</sup>Zr- labelled IgG radioactivity accumulated in the renal cortex. Relatively high accumulation in the kidneys was also observed in <sup>89</sup>Zr- labelled Fab-injected macaques, and renal autoradiographs of these animals showed that the renal cortex was the preferred accumulation site. However, [<sup>89</sup>Zr]Zr-DFO was rapidly excreted into the urine, whereas [<sup>89</sup>Zr]Zr-oxalate was highly accumulated in the epiphysis of the long bones and vertebral body.</div></div><div><h3>Conclusion</h3><div>In the non-human primate cynomolgus macaque, <sup>89</sup>Zr- labelled IgG accumulated in the kidneys and the liver. However, [<sup>89</sup>Zr]Zr-DFO and <sup>89</sup>Zr did not accumulate in these organs. This preclinical pharmacokinetic study performed with human IgG in a non-human primate model using PET is of great significance as it sheds light on the basic fate and distribution of <sup>89</sup>Zr- labelled IgG.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 109001"},"PeriodicalIF":3.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464388","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}
Pub Date : 2025-02-12DOI: 10.1016/j.nucmedbio.2025.108999
Ellinor Hansson , Chiara Timperanza , Holger Jensen , Björn Eriksson , Sture Lindegren , Emma Aneheim
Aim/introduction
Astatine-211 (211At) is one of the most promising nuclides for targeted alpha therapy. However, while several clinical trials are ongoing worldwide, some aspects of the element remain unexplored. This work aims to investigate changes in radiochemical yield over time, expressed as the number of 211At decays, post-dry distillation using two common astatination reactions.
Materials and methods
211At was purified from activated bismuth targets via dry distillation and eluted in chloroform. The solvated activity was then either evaporated to dryness or left in the chloroform eluate. Before chemical reactions, both forms of the starting material were allowed to age at room temperature for up to 28 h, correlating to 3 ∙ 1012 211At decays. All chemical reactions were subsequently started from a dry residue. Radiolabeling was carried out either via electrophilic destannylation of tri(methyl)phenylstannane, or via the nucleophilic substitution of bis(4-tert-butylphenyl)iodonium p-toluenesulfonate. Radiochemical yield was determined using a dual flow radiodetection HPLC method allowing direct yield quantification.
Results
In both cases, where 211At was stored either as a dry residue or in chloroform, radiochemical yields decreased with increasing amounts of radioactive decay. This was true both for nucleophilic and electrophilic astatinations. In the case of 211At stored in chloroform, the dose-yield relationship indicates a more rapid decrease for electrophilic astatination. However, decreases in radiochemical yield could be mitigated by increasing the precursor concentration, keeping yields constant above 80 % even when using 211At after 28 h, corresponding up to 3 ∙ 1012 211At decays. There is also an indication that higher amounts of oxidizing/reducing agents and redissolution of dry 211At in fresh chloroform may mitigate the loss in yield to some extent.
Conclusion
Radiochemical yields in labeling with 211At decrease over time post dry distillation independent if the 211At was kept dry or in chloroform. If high specific activity is a requirement for the final radiolabeled product, the most reliable way to maintain high yields is to perform the radiolabeling close in time after the dry distillation.
{"title":"Radiolabeling yield dependency of post-dry distillation decay of astatine-211","authors":"Ellinor Hansson , Chiara Timperanza , Holger Jensen , Björn Eriksson , Sture Lindegren , Emma Aneheim","doi":"10.1016/j.nucmedbio.2025.108999","DOIUrl":"10.1016/j.nucmedbio.2025.108999","url":null,"abstract":"<div><h3>Aim/introduction</h3><div>Astatine-211 (<sup>211</sup>At) is one of the most promising nuclides for targeted alpha therapy. However, while several clinical trials are ongoing worldwide, some aspects of the element remain unexplored. This work aims to investigate changes in radiochemical yield over time, expressed as the number of <sup>211</sup>At decays, post-dry distillation using two common astatination reactions.</div></div><div><h3>Materials and methods</h3><div><sup>211</sup>At was purified from activated bismuth targets via dry distillation and eluted in chloroform. The solvated activity was then either evaporated to dryness or left in the chloroform eluate. Before chemical reactions, both forms of the starting material were allowed to age at room temperature for up to 28 h, correlating to 3 ∙ 10<sup>12 211</sup>At decays. All chemical reactions were subsequently started from a dry residue. Radiolabeling was carried out either via electrophilic destannylation of tri(methyl)phenylstannane, or via the nucleophilic substitution of bis(4-<em>tert</em>-butylphenyl)iodonium <em>p</em>-toluenesulfonate. Radiochemical yield was determined using a dual flow radiodetection HPLC method allowing direct yield quantification.</div></div><div><h3>Results</h3><div>In both cases, where <sup>211</sup>At was stored either as a dry residue or in chloroform, radiochemical yields decreased with increasing amounts of radioactive decay. This was true both for nucleophilic and electrophilic astatinations. In the case of <sup>211</sup>At stored in chloroform, the dose-yield relationship indicates a more rapid decrease for electrophilic astatination. However, decreases in radiochemical yield could be mitigated by increasing the precursor concentration, keeping yields constant above 80 % even when using <sup>211</sup>At after 28 h, corresponding up to 3 ∙ 10<sup>12 211</sup>At decays. There is also an indication that higher amounts of oxidizing/reducing agents and redissolution of dry <sup>211</sup>At in fresh chloroform may mitigate the loss in yield to some extent.</div></div><div><h3>Conclusion</h3><div>Radiochemical yields in labeling with <sup>211</sup>At decrease over time post dry distillation independent if the <sup>211</sup>At was kept dry or in chloroform. If high specific activity is a requirement for the final radiolabeled product, the most reliable way to maintain high yields is to perform the radiolabeling close in time after the dry distillation.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 108999"},"PeriodicalIF":3.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420507","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}
Pub Date : 2025-02-12DOI: 10.1016/j.nucmedbio.2025.108998
František Trejtnar , Pavel Bárta , Ján Kozempel , Martin Vlk , Anna Ďurinová , Monika Kuchařová , Petr Pávek
The use of new radiopharmaceuticals labeled with lutetium-177 represents a successful translation of experimental results into clinical practice. Recent experimental data suggests that terbium-161 might well follow the example of lutetium-177 regarding applicability in nuclear medicine. Similarly to lutetium-177, the terbium-161 emits beta particles and gamma-radiation, although terbium-161 emits short-ranged conversion and Auger electrons, creating an effect that may eliminate smaller tumor metastases more effectively than lutetium-177. Terbium-161 may exert a higher radiobiological effect in the target tissues in comparison with lutetium-177, a difference which makes possible a reduction in the doses of radioactivity administered. Further, due to the similar chemical properties of lutetium-177 and terbium-161, similar radiolabeling techniques can be used. The differences found in preclinical experiments on radiotoxicity of the counterparts seem to be minor. Despite intensive progress, the number of preclinical studies on 161Tb-labeled agents is still not comparable to studies on lutetium-177. Clinical trials with 161Tb-labeled radiopharmaceuticals focused on the treatment of prostate cancer and selected neuroendocrine tumors have already begun, although none of them have been completed yet.
{"title":"Terbium-161 in nuclear medicine: Preclinical and clinical progress in comparison with lutetium-177","authors":"František Trejtnar , Pavel Bárta , Ján Kozempel , Martin Vlk , Anna Ďurinová , Monika Kuchařová , Petr Pávek","doi":"10.1016/j.nucmedbio.2025.108998","DOIUrl":"10.1016/j.nucmedbio.2025.108998","url":null,"abstract":"<div><div>The use of new radiopharmaceuticals labeled with lutetium-177 represents a successful translation of experimental results into clinical practice. Recent experimental data suggests that terbium-161 might well follow the example of lutetium-177 regarding applicability in nuclear medicine. Similarly to lutetium-177, the terbium-161 emits beta particles and gamma-radiation, although terbium-161 emits short-ranged conversion and Auger electrons, creating an effect that may eliminate smaller tumor metastases more effectively than lutetium-177. Terbium-161 may exert a higher radiobiological effect in the target tissues in comparison with lutetium-177, a difference which makes possible a reduction in the doses of radioactivity administered. Further, due to the similar chemical properties of lutetium-177 and terbium-161, similar radiolabeling techniques can be used. The differences found in preclinical experiments on radiotoxicity of the counterparts seem to be minor. Despite intensive progress, the number of preclinical studies on <sup>161</sup>Tb-labeled agents is still not comparable to studies on lutetium-177. Clinical trials with <sup>161</sup>Tb-labeled radiopharmaceuticals focused on the treatment of prostate cancer and selected neuroendocrine tumors have already begun, although none of them have been completed yet.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 108998"},"PeriodicalIF":3.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436479","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}
Pub Date : 2025-01-22DOI: 10.1016/j.nucmedbio.2025.108994
E.S. Kurakina , B.L. McNeil , J. Khushvaktov , N.T. Temerbulatova , N.A. Mirzayev , E.P. Magomedbekov , C. Hoehr , C.F. Ramogida , D.V. Filosofov , V. Radchenko
Introduction
Radiolanthanides 132La and 135La form a promising chemically matched theranostic pair. With a half-life of 18.95 h, 135La acts as the therapeutic isotope as it releases approximately 11 Auger electrons per decay, making it compatible with targeted Auger electron therapy (TAET), whereas 132La with half-life of 4.58 h undergoes positron emission making it compatible with imaging via positron emission tomography (PET).
Methods
132/135La were produced via irradiation of natural barium targets (99.9 %) with 12.8 MeV protons. A two-step separation scheme using extraction chromatographic resin TK200 (50–100 μm) and cation exchange resin Dowex 50Wx4 (200–400 mesh) was designed. Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify non-radioactive impurities in each fraction of the separation method. The distribution coefficients of La3+ in HNO3 on the TK200 resin and on both Dowex 50Wx8 (200–400 mesh) and Dowex 50Wx4 resins in ammonium α-hydroxyisobutyrate (pH 4.8) were determined, respectively.
Results
This novel separation scheme allowed for reliable separation of [132/135La]La3+ from the Ba2+ target material, resulting in a high radiochemical yield of 98.3 ± 2.1 % (n = 3) with the final elute being directly compatible with subsequent radiolabeling due to the use of ammonium α-hydroxyisobutyrate to eliminate steps in the radiopharmaceutical synthetic process.
{"title":"Production and purification of radiolabeling-ready 132/135La from the irradiation of metallic natBa targets with low energy protons","authors":"E.S. Kurakina , B.L. McNeil , J. Khushvaktov , N.T. Temerbulatova , N.A. Mirzayev , E.P. Magomedbekov , C. Hoehr , C.F. Ramogida , D.V. Filosofov , V. Radchenko","doi":"10.1016/j.nucmedbio.2025.108994","DOIUrl":"10.1016/j.nucmedbio.2025.108994","url":null,"abstract":"<div><h3>Introduction</h3><div>Radiolanthanides <sup>132</sup>La and <sup>135</sup>La form a promising chemically matched theranostic pair. With a half-life of 18.95 h, <sup>135</sup>La acts as the therapeutic isotope as it releases approximately 11 Auger electrons per decay, making it compatible with targeted Auger electron therapy (TAET), whereas <sup>132</sup>La with half-life of 4.58 h undergoes positron emission making it compatible with imaging via positron emission tomography (PET).</div></div><div><h3>Methods</h3><div><sup>132/135</sup>La were produced via irradiation of natural barium targets (99.9 %) with 12.8 MeV protons. A two-step separation scheme using extraction chromatographic resin TK200 (50–100 μm) and cation exchange resin Dowex 50Wx4 (200–400 mesh) was designed. Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify non-radioactive impurities in each fraction of the separation method. The distribution coefficients of La<sup>3+</sup> in HNO<sub>3</sub> on the TK200 resin and on both Dowex 50Wx8 (200–400 mesh) and Dowex 50Wx4 resins in ammonium α-hydroxyisobutyrate (pH 4.8) were determined, respectively.</div></div><div><h3>Results</h3><div>This novel separation scheme allowed for reliable separation of [<sup>132/135</sup>La]La<sup>3+</sup> from the Ba<sup>2+</sup> target material, resulting in a high radiochemical yield of 98.3 ± 2.1 % (<em>n</em> = 3) with the final elute being directly compatible with subsequent radiolabeling due to the use of ammonium α-hydroxyisobutyrate to eliminate steps in the radiopharmaceutical synthetic process.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 108994"},"PeriodicalIF":3.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075026","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}
Pub Date : 2025-01-22DOI: 10.1016/j.nucmedbio.2025.108997
Zongping Han , Min Yang , Lei Bi , Peizhen Ye , Yongshan Liu , Pengyuan He , Guolong Huang , Hongjun Jin , Jinyu Xia
Objective
The Sigma-1 receptor (Sig-1R), located in the mitochondrion-associated membranes (MAMs), is an important biomarker for endoplasmic reticulum (ER) stress and plays a crucial role in the advancement of metabolic-associated fatty liver disease (MAFLD). Despite its significance, current methods to monitor MAFLD progression and treatment response are limited. This study aims to address this gap by utilizing [18F]F-TZ3108, an effecient tracer targeting Sig-1R, to quantitatively assess MAFLD progression and the efficacy of a low-carbohydrate diet (LCD) as a potential therapeutic intervention.
Methods
The C57 BL/6 J mice were fed either a high-fat diet (HFD) or regular diet (CTR) for 12 weeks, and the progression of MAFLD was continuously monitored at 0, 4, 8, 12 weeks via [18F]F-TZ3108 positron emission tomography/computed tomography (PET/CT) and ex vivo assessment. After confirming successful induction, LDC intervention was administered in the HFD group for 2 weeks. And relevant post-treatment evaluations were also performed.
Results
PET/CT revealed a continuous decline in the hepatic binding potential (BPND) of [18F]F-TZ3108 in mice in the HFD group during the induction period, when compared with the BPND in the CTR group. This reduction was significant after the 4th week of induction (p < 0.05). Furthermore, following intervention with LCD, there was a significant improvement in BPND (LCD vs HFD, p = 0.001).
Conclusions
The results of this study demonstrate that LCD therapy effectively mitigates MAFLD progression. Furthermore, the use of PET imaging with [18F]F-TZ3108 provides a reliable, non-invasive method for monitoring the progression and treatment response of MAFLD, offering significant potential for early detection and personalized treatment evaluation.
{"title":"Quantitative imaging using [18F]F-TZ3108 to assess metabolic-associated fatty liver disease progression and low-carbohydrate diet efficacy","authors":"Zongping Han , Min Yang , Lei Bi , Peizhen Ye , Yongshan Liu , Pengyuan He , Guolong Huang , Hongjun Jin , Jinyu Xia","doi":"10.1016/j.nucmedbio.2025.108997","DOIUrl":"10.1016/j.nucmedbio.2025.108997","url":null,"abstract":"<div><h3>Objective</h3><div>The Sigma-1 receptor (Sig-1R), located in the mitochondrion-associated membranes (MAMs), is an important biomarker for endoplasmic reticulum (ER) stress and plays a crucial role in the advancement of metabolic-associated fatty liver disease (MAFLD). Despite its significance, current methods to monitor MAFLD progression and treatment response are limited. This study aims to address this gap by utilizing [<sup>18</sup>F]F-TZ3108, an effecient tracer targeting Sig-1R, to quantitatively assess MAFLD progression and the efficacy of a low-carbohydrate diet (LCD) as a potential therapeutic intervention.</div></div><div><h3>Methods</h3><div>The C57 BL/6 J mice were fed either a high-fat diet (HFD) or regular diet (CTR) for 12 weeks, and the progression of MAFLD was continuously monitored at 0, 4, 8, 12 weeks via [<sup>18</sup>F]F-TZ3108 positron emission tomography/computed tomography (PET/CT) and ex vivo assessment. After confirming successful induction, LDC intervention was administered in the HFD group for 2 weeks. And relevant post-treatment evaluations were also performed.</div></div><div><h3>Results</h3><div>PET/CT revealed a continuous decline in the hepatic binding potential (BP<sub>ND</sub>) of [<sup>18</sup>F]F-TZ3108 in mice in the HFD group during the induction period, when compared with the BP<sub>ND</sub> in the CTR group. This reduction was significant after the 4th week of induction (<em>p</em> < 0.05). Furthermore, following intervention with LCD, there was a significant improvement in BP<sub>ND</sub> (LCD vs HFD, <em>p</em> = 0.001).</div></div><div><h3>Conclusions</h3><div>The results of this study demonstrate that LCD therapy effectively mitigates MAFLD progression. Furthermore, the use of PET imaging with [<sup>18</sup>F]F-TZ3108 provides a reliable, non-invasive method for monitoring the progression and treatment response of MAFLD, offering significant potential for early detection and personalized treatment evaluation.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 108997"},"PeriodicalIF":3.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350265","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}
Pub Date : 2025-01-22DOI: 10.1016/j.nucmedbio.2025.108996
Yuki Tomonari, Hiroyuki Ohba, Hideo Tsukada
Background
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-tert-butyl-4-chloro-5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF).
Results
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.
Conclusions
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.
{"title":"[18F]BCPP-EF positron emission tomography of rat ovaries for evaluation of mitochondrial function","authors":"Yuki Tomonari, Hiroyuki Ohba, 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-<sup>18</sup>F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([<sup>18</sup>F]BCPP-EF).</div></div><div><h3>Results</h3><div>Aged rats, whose ovary function decline, exhibited a higher uptake of [<sup>18</sup>F]BCPP-EF in the ovary than young rats, and this high uptake in aged rats was suppressed by mitoquinone, a superoxide scavenger. Increased [<sup>18</sup>F]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 [<sup>18</sup>F]BCPP-EF can detect age-related changes in essential ovarian function evaluated by ovarian fibrosis. Therefore, [<sup>18</sup>F]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}