EJNMMI Research最新文献

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Advancements in theranostic applications: exploring the role of fibroblast activation protein inhibition tracers in enhancing thyroid health assessment. 治疗学应用的进展:探索成纤维细胞活化蛋白抑制示踪剂在加强甲状腺健康评估中的作用。
IF 3.2 3区 医学
EJNMMI Research Pub Date : 2023-12-22 DOI: 10.1186/s13550-023-01060-8
Yuhua Wang, Ye Liu, Huixia Geng, Wanchun Zhang
{"title":"Advancements in theranostic applications: exploring the role of fibroblast activation protein inhibition tracers in enhancing thyroid health assessment.","authors":"Yuhua Wang, Ye Liu, Huixia Geng, Wanchun Zhang","doi":"10.1186/s13550-023-01060-8","DOIUrl":"10.1186/s13550-023-01060-8","url":null,"abstract":"<p><strong>Background: </strong>The diagnostic accuracy of [<sup>18</sup>F]-fluorodeoxyglucose ([<sup>18</sup>F]-FDG) positron emission tomography imaging in accurately identifying thyroid lesions is limited, primarily due to the physiological uptake of normal head and neck tissues and inflammatory uptake in lymph nodes. Since fibroblast activating protein is highly expressed in tumors and largely unexpressed in normal tissues, quinoline-based fibroblast activating protein inhibitors (FAPI) have emerged as promising tools in the diagnosis of cancer and other medical conditions. Several studies have reported on the feasibility and value of FAPI in thyroid cancer.</p><p><strong>Main body: </strong>In this narrative review, we summarize the current literature on state-of-the-art FAPI positron emission tomography imaging for thyroid cancer and fibroblast activating protein-targeted radionuclide therapy. We provide an overview of FAPI uptake in normal thyroid tissue, thyroid cancer and its metastases. Additionally, we highlight the difference between FAPI uptake and [<sup>18</sup>F]-FDG uptake in thyroid lesions. Furthermore, we discuss the therapeutic value of FAPI in iodine-refractory thyroid cancer.</p><p><strong>Conclusion: </strong>The utilization of fibroblast activating protein inhibitors in thyroid cancer holds significant promise, offering clinicians valuable insights for more precise diagnose choices and treatments strategies in the future.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10739649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[18F]FDOPA PET/CT is superior to [68Ga]DOTATOC PET/CT in diagnostic imaging of pheochromocytoma 在嗜铬细胞瘤的诊断成像中,[18F]FDOPA PET/CT 优于[68Ga]DOTATOC PET/CT
IF 3.2 3区 医学
EJNMMI Research Pub Date : 2023-12-18 DOI: 10.1186/s13550-023-01056-4
Peter Iversen, Stine Kramer, Andreas Ebbehoj, Esben Søndergaard, Kirstine Stochholm, Per Løgstrup Poulsen, Karin Hjorthaug
{"title":"[18F]FDOPA PET/CT is superior to [68Ga]DOTATOC PET/CT in diagnostic imaging of pheochromocytoma","authors":"Peter Iversen, Stine Kramer, Andreas Ebbehoj, Esben Søndergaard, Kirstine Stochholm, Per Løgstrup Poulsen, Karin Hjorthaug","doi":"10.1186/s13550-023-01056-4","DOIUrl":"https://doi.org/10.1186/s13550-023-01056-4","url":null,"abstract":"Both [18F]FDOPA (FDOPA) and [68Ga]DOTATOC PET/CT (DOTATOC) are widely used for detection of pheochromocytomas/paraganglioma (PPGL). However, direct comparisons of the performance of the two tracers are only available in small series. We conducted a retrospective comparative analysis of FDOPA and DOTATOC to assess their sensitivity and accuracy in detecting PPGL when administered based on suspicion of PPGL. We consecutively included patients referred on suspicion of PPGL or PPGL recurrence who were scanned with both FDOPA and DOTATOC. Both scans were reviewed retrospectively by two experienced observers, who were blinded to the final diagnosis. The assessment was made both visually and quantitatively. The final diagnosis was primarily based on pathology. In total, 113 patients were included (97 suspected of primary PPGL and 16 suspected of recurrence). Of the 97 patients, 51 had pheochromocytomas (PCC) (in total 55 lesions) and 6 had paragangliomas (PGL) (in total 7 lesions). FDOPA detected and correctly localized all 55 PCC, while DOTATOC only detected 25 (sensitivity 100% vs. 49%, p < 0.0001; specificity 95% vs. 98%, p = 1.00). The negative predictive value (100% vs. 63%, p < 0.001) and diagnostic accuracy (98% vs. 70%, p < 0.01) were higher for FDOPA compared to DOTATOC. FDOPA identified 6 of 6 patients with hormone producing PGL, of which one was negative on DOTATOC. Diagnostic performances of FDOPA and DOTATOC were similar in the 16 patients with previous PPGL suspected of recurrence. FDOPA is superior to DOTATOC for localization of PCC. In contrast to DOTATOC, FDOPA also identified all PGL but with a limited number of patient cases.","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138741047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Preclinical evaluation of Affibody molecule for PET imaging of human pancreatic islets derived from stem cells 用于干细胞提取的人胰岛 PET 成像的 Affibody 分子的临床前评估
IF 3.2 3区 医学
EJNMMI Research Pub Date : 2023-12-15 DOI: 10.1186/s13550-023-01057-3
Pierre Cheung, Julia Thorngren, Bo Zhang, Svitlana Vasylovska, Francesco Lechi, Jonas Persson, Stefan Ståhl, John Löfblom, Olle Korsgren, Jonas Eriksson, Joey Lau, Olof Eriksson
{"title":"Preclinical evaluation of Affibody molecule for PET imaging of human pancreatic islets derived from stem cells","authors":"Pierre Cheung, Julia Thorngren, Bo Zhang, Svitlana Vasylovska, Francesco Lechi, Jonas Persson, Stefan Ståhl, John Löfblom, Olle Korsgren, Jonas Eriksson, Joey Lau, Olof Eriksson","doi":"10.1186/s13550-023-01057-3","DOIUrl":"https://doi.org/10.1186/s13550-023-01057-3","url":null,"abstract":"Beta-cell replacement methods such as transplantation of isolated donor islets have been proposed as a curative treatment of type 1 diabetes, but widespread application is challenging due to shortages of donor tissue and the need for continuous immunosuppressive treatments. Stem-cell-derived islets have been suggested as an alternative source of beta cells, but face transplantation protocols optimization difficulties, mainly due to a lack of available methods and markers to directly monitor grafts survival, as well as their localization and function. Molecular imaging techniques and particularly positron emission tomography has been suggested as a tool for monitoring the fate of islets after clinical transplantation. The integral membrane protein DGCR2 has been demonstrated to be a potential pancreatic islet biomarker, with specific expression on insulin-positive human embryonic stem-cell-derived pancreatic progenitor cells. The candidate Affibody molecule ZDGCR2:AM106 was radiolabeled with fluorine-18 using a novel click chemistry-based approach. The resulting positron emission tomography tracer [18F]ZDGCR2:AM106 was evaluated for binding to recombinant human DGCR2 and cryosections of stem-cell-derived islets, as well as in vivo using an immune-deficient mouse model transplanted with stem-cell-derived islets. Biodistribution of the [18F]ZDGCR2:AM106 was also assessed in healthy rats and pigs. [18F]ZDGCR2:AM106 was successfully synthesized with high radiochemical purity and yield via a pretargeting approach. [18F]ZDGCR2:AM106 retained binding to recombinant human DCGR2 as well as to cryosectioned stem-cell-derived islets, but in vivo binding to native pancreatic tissue in both rat and pig was low. However, in vivo uptake of [18F]ZDGCR2:AM106 in stem-cell-derived islets transplanted in the immunodeficient mice was observed, albeit only within the early imaging frames after injection of the radiotracer. Targeting of DGCR2 is a promising approach for in vivo detection of stem-cell-derived islets grafts by molecular imaging. The synthesis of [18F]ZDGCR2:AM106 was successfully performed via a pretargeting method to label a site-specific covalently bonded fluorine-18 to the Affibody molecule. However, the rapid washout of [18F]ZDGCR2:AM106 from the stem-cell-derived islets graft indicates that dissociation kinetics can be improved. Further studies using alternative binders of similar classes with improved binding potential are warranted.","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138690022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of a novel model for atherosclerosis imaging: the apolipoprotein E-deficient rat 动脉粥样硬化成像新模型的特征:脂蛋白 E 缺乏大鼠
IF 3.2 3区 医学
EJNMMI Research Pub Date : 2023-12-11 DOI: 10.1186/s13550-023-01055-5
Jürgen W. A. Sijbesma, Aren van Waarde, Sebastiaan Kristensen, Ilse Kion, Uwe J. F. Tietge, Jan-Luuk Hillebrands, Marian L. C. Bulthuis, Hendrik Buikema, Dalibor Nakladal, Marit Westerterp, Fan Liu, Hendrikus H. Boersma, Rudi A. J. O. Dierckx, Riemer H. J. A. Slart
{"title":"Characterization of a novel model for atherosclerosis imaging: the apolipoprotein E-deficient rat","authors":"Jürgen W. A. Sijbesma, Aren van Waarde, Sebastiaan Kristensen, Ilse Kion, Uwe J. F. Tietge, Jan-Luuk Hillebrands, Marian L. C. Bulthuis, Hendrik Buikema, Dalibor Nakladal, Marit Westerterp, Fan Liu, Hendrikus H. Boersma, Rudi A. J. O. Dierckx, Riemer H. J. A. Slart","doi":"10.1186/s13550-023-01055-5","DOIUrl":"https://doi.org/10.1186/s13550-023-01055-5","url":null,"abstract":"The apolipoprotein E-deficient (apoE−/−) mouse is a well-established model for studying atherosclerosis. However, its small size limits its use in longitudinal positron emission tomography (PET) imaging studies. Recently, the apoE−/− rat has emerged as an alternative. With this study, we investigate the feasibility of using apoE−/− rats as an in vivo model for longitudinal atherosclerotic PET/CT imaging. ApoE−/− rats showed significantly higher [18F]FDG uptake than controls in the aortic arch (+ 18.5%, p < 0.001) and abdominal aorta (+ 31.0%, p < 0.001) at weeks 12, 26, and 51. ApoE−/− rats exhibited hypercholesterolemia, as evidenced by plasma cholesterol levels that were up to tenfold higher, and total hepatic cholesterol levels that were up to threefold higher than the control rats at the end of the study. Fast protein liquid chromatography cholesterol profiling indicated very high levels of pro-atherogenic apoB-containing very low-density lipoprotein and low-density lipoprotein fractions in the apoE−/− rats. Atherosclerotic lesions cover 19.9% of the surface of the aortic arch (p = 0.0013), and there was a significantly higher subendothelial accumulation of ED1-positive macrophages in the abdominal aorta of the apoE−/− rats compared to control rats (Ctrl) (p = 0.01). No differences in neutral sterols were observed but higher levels of bile acids were found in the apoE−/− rats. These data demonstrate early signs of hypercholesterolemia, high levels of bile acids, the development of atherosclerotic lesions, and macrophage accumulation in apoE−/− rats. Therefore, this model shows promise for atherosclerosis imaging studies.","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138566771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
18F-FDG PET/CT-based deep learning radiomics predicts 5-years disease-free survival after failure to achieve pathologic complete response to neoadjuvant chemotherapy in breast cancer. 基于18F-FDG PET/CT的深度学习放射组学预测乳腺癌新辅助化疗未获病理完全反应后的5年无病生存期。
IF 3.2 3区 医学
EJNMMI Research Pub Date : 2023-12-06 DOI: 10.1186/s13550-023-01053-7
Xingxing Zheng, Yuhong Huang, Yingyi Lin, Teng Zhu, Jiachen Zou, Shuxia Wang, Kun Wang
{"title":"<sup>18</sup>F-FDG PET/CT-based deep learning radiomics predicts 5-years disease-free survival after failure to achieve pathologic complete response to neoadjuvant chemotherapy in breast cancer.","authors":"Xingxing Zheng, Yuhong Huang, Yingyi Lin, Teng Zhu, Jiachen Zou, Shuxia Wang, Kun Wang","doi":"10.1186/s13550-023-01053-7","DOIUrl":"10.1186/s13550-023-01053-7","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to assess whether a combined model incorporating radiomic and depth features extracted from PET/CT can predict disease-free survival (DFS) in patients who failed to achieve pathologic complete response (pCR) after neoadjuvant chemotherapy.</p><p><strong>Results: </strong>This study retrospectively included one hundred and five non-pCR patients. After a median follow-up of 71 months, 15 and 7 patients experienced recurrence and death, respectively. The primary tumor volume underwent feature extraction, yielding a total of 3644 radiomic features and 4096 depth features. The modeling procedure employed Cox regression for feature selection and utilized Cox proportional-hazards models to make predictions on DFS. Time-dependent receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were utilized to evaluate and compare the predictive performance of different models. 2 clinical features (RCB, cT), 4 radiomic features, and 7 depth features were significant predictors of DFS and were included to develop models. The integrated model incorporating RCB, cT, and radiomic and depth features extracted from PET/CT images exhibited the highest accuracy for predicting 5-year DFS in the training (AUC 0.943) and the validation cohort (AUC 0.938).</p><p><strong>Conclusion: </strong>The integrated model combining radiomic and depth features extracted from PET/CT images can accurately predict 5-year DFS in non-pCR patients. It can help identify patients with a high risk of recurrence and strengthen adjuvant therapy to improve survival.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10697916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single time point quantitation of cerebral glucose metabolism by FDG-PET without arterial sampling. 不经动脉取样的FDG-PET单时间点脑糖代谢定量。
IF 3.2 3区 医学
EJNMMI Research Pub Date : 2023-11-30 DOI: 10.1186/s13550-023-01049-3
Paul Cumming, André H Dias, Lars C Gormsen, Allan K Hansen, Ian Alberts, Axel Rominger, Ole L Munk, Hasan Sari
{"title":"Single time point quantitation of cerebral glucose metabolism by FDG-PET without arterial sampling.","authors":"Paul Cumming, André H Dias, Lars C Gormsen, Allan K Hansen, Ian Alberts, Axel Rominger, Ole L Munk, Hasan Sari","doi":"10.1186/s13550-023-01049-3","DOIUrl":"10.1186/s13550-023-01049-3","url":null,"abstract":"<p><strong>Background: </strong>Until recently, quantitation of the net influx of 2-[<sup>18</sup>F]fluorodeoxyglucose (FDG) to brain (K<sub>i</sub>) and the cerebrometabolic rate for glucose (CMR<sub>glc</sub>) required serial arterial blood sampling in conjunction with dynamic positron emission tomography (PET) recordings. Recent technical innovations enable the identification of an image-derived input function (IDIF) from vascular structures, but are frequently still encumbered by the need for interrupted sequences or prolonged recordings that are seldom available outside of a research setting. In this study, we tested simplified methods for quantitation of FDG-K<sub>i</sub> by linear graphic analysis relative to the descending aorta IDIF in oncology patients examined using a Biograph Vision 600 PET/CT with continuous bed motion (Aarhus) or using a recently installed Biograph Vision Quadra long-axial field-of-view (FOV) scanner (Bern).</p><p><strong>Results: </strong>Correlation analysis of the coefficients of a tri-exponential decomposition of the IDIFs measured during 67 min revealed strong relationships among the total area under the curve (AUC), the terminal normalized arterial integral (theta<sub>(52-67 min)</sub>), and the terminal image-derived arterial FDG concentration (Ca<sub>(52-67 min)</sub>). These relationships enabled estimation of the missing AUC from late recordings of the IDIF, from which we then calculated FDG-K<sub>i</sub> in brain by two-point linear graphic analysis using a population mean ordinate intercept and the single late frame. Furthermore, certain aspects of the IDIF data from Aarhus showed a marked age-dependence, which was not hitherto reported for the case of FDG pharmacokinetics.</p><p><strong>Conclusions: </strong>The observed interrelationships between pharmacokinetic parameters in the IDIF measured during the PET recording support quantitation of FDG-K<sub>i</sub> in brain using a single averaged frame from the interval 52-67 min post-injection, with minimal error relative to calculation from the complete dynamic sequences.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10689590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[18F]FDG PET-MR characterization of aortitis in the IL1rn-/- mouse model of giant-cell arteritis. [18F] il - 1rn-/-小鼠巨细胞动脉炎模型的FDG PET-MR表征。
IF 3.2 3区 医学
EJNMMI Research Pub Date : 2023-11-29 DOI: 10.1186/s13550-023-01039-5
Samuel Deshayes, Caroline Baugé, Pierre-Antoine Dupont, Christophe Simard, Hanan Rida, Hubert de Boysson, Alain Manrique, Achille Aouba
{"title":"[<sup>18</sup>F]FDG PET-MR characterization of aortitis in the IL1rn<sup>-/-</sup> mouse model of giant-cell arteritis.","authors":"Samuel Deshayes, Caroline Baugé, Pierre-Antoine Dupont, Christophe Simard, Hanan Rida, Hubert de Boysson, Alain Manrique, Achille Aouba","doi":"10.1186/s13550-023-01039-5","DOIUrl":"10.1186/s13550-023-01039-5","url":null,"abstract":"<p><strong>Background: </strong>Metabolic imaging is routinely used to demonstrate aortitis in patients with giant-cell arteritis. We aimed to investigate the preclinical model of aortitis in BALB/c IL1rn<sup>-/-</sup> mice using [<sup>18</sup>F]fluorodeoxyglucose ([<sup>18</sup>F]FDG) positron emission tomography-magnetic resonance (PET-MR), gamma counting and immunostaining. We used 15 first-generation specific and opportunistic pathogen-free (SOPF) 9-week-old IL1rn<sup>-/-</sup> mice, 15 wild-type BALB/cAnN mice and 5 s-generation specific pathogen-free (SPF) 9-week-old IL1rn<sup>-/-</sup>. Aortic [<sup>18</sup>F]FDG uptake was assessed as the target-to-background ratio (TBR) using time-of-flight MR angiography as vascular landmarks.</p><p><strong>Results: </strong>[<sup>18</sup>F]FDG uptake measured by PET or gamma counting was similar in the first-generation SOPF IL1rn<sup>-/-</sup> mice and the wild-type group (p > 0.05). However, the first-generation IL1rn<sup>-/-</sup> mice exhibited more interleukin-1β (p = 0.021)- and interleukin-6 (p = 0.019)-positive cells within the abdominal aorta than the wild-type mice. In addition, the second-generation SPF group exhibited significantly higher TBR (p = 0.0068) than the wild-type mice on the descending thoracic aorta, unlike the first-generation SOPF IL1rn<sup>-/-</sup> mice.</p><p><strong>Conclusions: </strong>In addition to the involvement of interleukin-1β and -6 in IL1rn<sup>-/-</sup> mouse aortitis, this study seems to validate [<sup>18</sup>F]FDG PET-MR as a useful tool for noninvasive monitoring of aortitis in this preclinical model.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessment of hypoxia and oxidative-related changes in a lung-derived brain metastasis model by [64Cu][Cu(ATSM)] PET and proteomic studies. 通过[64Cu][Cu(ATSM)] PET和蛋白质组学研究评估肺源性脑转移模型中的缺氧和氧化相关变化。
IF 3.2 3区 医学
EJNMMI Research Pub Date : 2023-11-25 DOI: 10.1186/s13550-023-01052-8
Jade Fantin, Jérôme Toutain, Elodie A Pérès, Benoit Bernay, Sarina Maya Mehani, Charly Helaine, Mickael Bourgeois, Carole Brunaud, Laurent Chazalviel, Julien Pontin, Aurélien Corroyer-Dulmont, Samuel Valable, Michel Cherel, Myriam Bernaudin
{"title":"Assessment of hypoxia and oxidative-related changes in a lung-derived brain metastasis model by [<sup>64</sup>Cu][Cu(ATSM)] PET and proteomic studies.","authors":"Jade Fantin, Jérôme Toutain, Elodie A Pérès, Benoit Bernay, Sarina Maya Mehani, Charly Helaine, Mickael Bourgeois, Carole Brunaud, Laurent Chazalviel, Julien Pontin, Aurélien Corroyer-Dulmont, Samuel Valable, Michel Cherel, Myriam Bernaudin","doi":"10.1186/s13550-023-01052-8","DOIUrl":"10.1186/s13550-023-01052-8","url":null,"abstract":"<p><strong>Background: </strong>Brain metastases (BM) are the most frequent malignant brain tumors. The aim of this study was to characterize the tumor microenvironment (TME) of BM and particularly hypoxia and redox state, known to play a role in tumor growth and treatment resistance with multimodal PET and MRI imaging, immunohistochemical and proteomic approaches in a human lung cancer (H2030-BrM3)-derived BM model in rats.</p><p><strong>Results: </strong>First, in vitro studies confirmed that H2030-BrM3 cells respond to hypoxia with increasing expression of HIF-1, HIF-2 and their target genes. Proteomic analyses revealed, among expression changes, proteins associated with metabolism, oxidative stress, metal response and hypoxia signaling in particular in cortical BM. [<sup>64</sup>Cu][Cu(ATSM)] PET revealed a significant uptake by cortical BM (p < 0.01), while no uptake is observed in striatal BM 23 days after tumor implantation. Pimonidazole, HIF-1α, HIF-2α, CA-IX as well as GFAP, CTR1 and DMT1 immunostainings are positive in both BM.</p><p><strong>Conclusion: </strong>Overall, [<sup>64</sup>Cu][Cu(ATSM)] imaging and proteomic results showed the presence of hypoxia and protein expression changes linked to hypoxia and oxidative stress in BM, which are more pronounced in cortical BM compared to striatal BM. Moreover, it emphasized the interest of [<sup>64</sup>Cu][Cu(ATSM)] PET to characterize TME of BM and depict inter-metastasis heterogeneity that could be useful to guide treatments.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biological efficacy of simulated radiolabeled Lipiodol® ultra-fluid and microspheres for various beta emitters: study based on VX2 tumors. 模拟放射性标记Lipiodol®超流体和微球对各种β发射器的生物学功效:基于VX2肿瘤的研究。
IF 3.2 3区 医学
EJNMMI Research Pub Date : 2023-11-23 DOI: 10.1186/s13550-023-01051-9
Arnaud Dieudonné, Stéphanie Becker, Miguel Soares, Claire Hollenbeck, Marie-Christine De Goltstein, Pierre Vera, Robin Santus
{"title":"Biological efficacy of simulated radiolabeled Lipiodol® ultra-fluid and microspheres for various beta emitters: study based on VX2 tumors.","authors":"Arnaud Dieudonné, Stéphanie Becker, Miguel Soares, Claire Hollenbeck, Marie-Christine De Goltstein, Pierre Vera, Robin Santus","doi":"10.1186/s13550-023-01051-9","DOIUrl":"10.1186/s13550-023-01051-9","url":null,"abstract":"<p><strong>Background: </strong>Radioembolization is one therapeutic option for the treatment of locally early-stage hepatocellular carcinoma. The aim of this study was to evaluate the distribution of Lipiodol® ultra-fluid and microspheres and to simulate their effectiveness with different beta emitters (<sup>90</sup>Y, <sup>188</sup>Re, <sup>32</sup>P, <sup>166</sup>Ho, <sup>131</sup>I, and <sup>177</sup>Lu) on VX2 tumors implanted in the liver of 30 New Zealand rabbits.</p><p><strong>Results: </strong>Twenty-three out of 30 rabbits had exploitable data: 14 in the group that received Lipiodol® ultra-fluid (group L), 6 in the group that received microspheres (group M), and 3 in the control group (group C). The histologic analysis showed that the Lipiodol® ultra-fluid distributes homogeneously in the tumor up to 12 days after injection. The X-ray μCT images showed that Lipiodol® ultra-fluid has a more distal penetration in the tumor than microspheres. The entropy (disorder of the system) in the L group was significantly higher than in the M group (4.06 vs 2.67, p = 0.01). Equivalent uniform biological effective doses (EUBED) for a tumor-absorbed dose of 100 Gy were greater in the L group but without statistical significance except for <sup>177</sup>Lu (p = 0.03). The radionuclides ranking by EUBED (from high to low) was <sup>90</sup>Y, <sup>188</sup>Re, <sup>32</sup>P, <sup>166</sup>Ho, <sup>131</sup>I, and <sup>177</sup>Lu.</p><p><strong>Conclusions: </strong>This study showed a higher ability of Lipiodol® ultra-fluid to penetrate the tumor that translated into a higher EUBED. This study confirms <sup>90</sup>Y as a good candidate for radioembolization, although <sup>32</sup>P, <sup>166</sup>Ho, and <sup>188</sup>Re can achieve similar results.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138294930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of [89Zr]Zr-hCD103.Fab01A and [68Ga]Ga-hCD103.Fab01A for PET imaging to noninvasively assess cancer reactive T cell infiltration: Fab-based CD103 immunoPET. [89Zr]Zr-hCD103的研制。[68Ga]Ga-hCD103。Fab01A用于PET成像无创评估癌症反应性T细胞浸润:基于fab的CD103免疫PET
IF 3.2 3区 医学
EJNMMI Research Pub Date : 2023-11-20 DOI: 10.1186/s13550-023-01043-9
Xiaoyu Fan, Marta A Ważyńska, Arjan Kol, Noemi Perujo Holland, Bruna Fernandes, Sander M J van Duijnhoven, Annechien Plat, Hans van Eenennaam, Philip H Elsinga, Hans W Nijman, Marco de Bruyn
{"title":"Development of [<sup>89</sup>Zr]Zr-hCD103.Fab01A and [<sup>68</sup>Ga]Ga-hCD103.Fab01A for PET imaging to noninvasively assess cancer reactive T cell infiltration: Fab-based CD103 immunoPET.","authors":"Xiaoyu Fan, Marta A Ważyńska, Arjan Kol, Noemi Perujo Holland, Bruna Fernandes, Sander M J van Duijnhoven, Annechien Plat, Hans van Eenennaam, Philip H Elsinga, Hans W Nijman, Marco de Bruyn","doi":"10.1186/s13550-023-01043-9","DOIUrl":"10.1186/s13550-023-01043-9","url":null,"abstract":"<p><strong>Background: </strong>CD103 is an integrin specifically expressed on the surface of cancer-reactive T cells. The number of CD103+ T cells significantly increases during successful immunotherapy and might therefore be an attractive biomarker for noninvasive PET imaging of immunotherapy response. Since the long half-life of antibodies preclude repeat imaging of CD103+ T cell dynamics early in therapy, we therefore here explored PET imaging with CD103 Fab fragments radiolabeled with a longer (<sup>89</sup>Zr) and shorter-lived radionuclide (<sup>68</sup>Ga).</p><p><strong>Methods: </strong>Antihuman CD103 Fab fragment Fab01A was radiolabeled with <sup>89</sup>Zr or <sup>68</sup>Ga, generating [<sup>89</sup>Zr]Zr-hCD103.Fab01A and [<sup>68</sup>Ga]Ga-hCD103.Fab01A, respectively. In vivo evaluation of these tracers was performed in male nude mice (BALB/cOlaHsd-Foxn1nu) with established CD103-expressing CHO (CHO.CD103) or CHO-wildtype (CHO.K1) xenografts, followed by serial PET imaging and ex vivo bio-distribution.</p><p><strong>Results: </strong>[<sup>89</sup>Zr]Zr-hCD103.Fab01A showed high tracer uptake in CD103+ xenografts as early as 3 h post-injection. However, the background signal remained high in the 3- and 6-h scans. The background was relatively low at 24 h after injection with sufficient tumor uptake. [<sup>68</sup>Ga]Ga-hCD103.Fab01Ashowed acceptable uptake and signal-to-noise ratio in CD103+ xenografts after 3 h, which decreased at subsequent time points.</p><p><strong>Conclusion: </strong>[<sup>89</sup>Zr]Zr-hCD103.Fab01A demonstrated a relatively low background and high xenograft uptake in scans as early as 6 h post-injection and could be explored for repeat imaging during immunotherapy in clinical trials. <sup>18</sup>F or <sup>64</sup>Cu could be explored as alternative to <sup>68</sup>Ga in optimizing half-life and radiation burden of the tracer.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10661679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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