European Journal of Nuclear Medicine and Molecular Imaging最新文献

{"title":"Targeting Fn14 as a therapeutic target for cachexia reprograms the glycolytic pathway in tumour and brain in mice.","authors":"Ingrid Julienne Georgette Burvenich, Laura Danielle Osellame, Angela Rigopoulos, Nhi Huynh, Zhipeng Cao, Nicholas Johannes Hoogenraad, Andrew Mark Scott","doi":"10.1007/s00259-024-06836-1","DOIUrl":"10.1007/s00259-024-06836-1","url":null,"abstract":"<p><strong>Purpose: </strong>Cachexia is a complex syndrome characterized by unintentional weight loss, progressive muscle wasting and loss of appetite. Anti-Fn14 antibody (mAb 002) targets the TWEAK receptor (Fn14) in murine models of cancer cachexia and can extend the lifespan of mice by restoring the body weight of mice. Here, we investigated glucose metabolic changes in murine models of cachexia via [¹⁸F]FDG PET imaging, to explore whether Fn14 plays a role in the metabolic changes that occur during cancer cachexia.</p><p><strong>Methods: </strong>[¹⁸F]FDG PET/MRI imaging was performed in cachexia-inducing tumour models versus models that do not induce cachexia. SUV_average was calculated for all tumours via volume of interest (VOI) analysis of PET/MRI overlay images using PMOD software.</p><p><strong>Results: </strong>[¹⁸F]FDG PET imaging demonstrated increased tumour and brain uptake in cachectic versus non-cachectic tumour-bearing mice. Therapy with mAb 002 was able to reduce [¹⁸F]FDG uptake in tumours (P < 0.05, n = 3). Fn14 KO tumours did not induce body weight loss and did not show an increase in [¹⁸F]FDG tumour and brain uptake over time. In non-cachectic mice bearing Fn14 KO tumours, [¹⁸F]FDG tumour uptake was significantly lower (P < 0.01) than in cachectic mice bearing Fn14 WT counterparts. As a by-product of glucose metabolism, l-lactate production was also increased in cachexia-inducing tumours expressing Fn14.</p><p><strong>Conclusion: </strong>Our results demonstrate that Fn14 receptor activation is linked to glucose metabolism of cachexia-inducing tumours.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting of immune checkpoint regulator V-domain Ig suppressor of T-cell activation (VISTA) with ⁸⁹Zr-labelled CI-8993.","authors":"Ingrid Julienne Georgette Burvenich, Christian Werner Wichmann, Alexander Franklin McDonald, Nancy Guo, Angela Rigopoulos, Nhi Huynh, Mary Vail, Stacey Allen, Graeme Joseph O'Keefe, Fiona Elizabeth Scott, Raul Soikes, Steven Angelides, Reinhard von Roemeling, Andrew Mark Scott","doi":"10.1007/s00259-024-06854-z","DOIUrl":"10.1007/s00259-024-06854-z","url":null,"abstract":"<p><strong>Background: </strong>CI-8993 is a fully human IgG1κ monoclonal antibody (mAb) that binds specifically to immune checkpoint molecule VISTA (V-domain Ig suppressor of T-cell activation). Phase I safety has been established in patients with advanced cancer (NCT02671955). To determine the pharmacokinetics and biodistribution of CI-8993 in patients, we aimed to develop ⁸⁹Zr-labelled CI-8993 and validate PET imaging and quantitation in preclinical models prior to a planned human bioimaging trial.</p><p><strong>Methods: </strong>CI-8993 and human isotype IgG1 control were conjugated to the metal ion chelator p-isothiocyanatobenzyl-desferrioxamine (Df). Quality of conjugates were assessed by SE-HPLC, SDS-PAGE, and FACS. After radiolabelling with zirconium-89 (⁸⁹Zr), radioconjugates were assessed for radiochemical purity, immunoreactivity, antigen binding affinity, and serum stability in vitro. [⁸⁹Zr]Zr-Df-CI-8993 alone (1 mg/kg, 4.6 MBq) or in combination with 30 mg/kg unlabelled CI-8993, as well as isotype control [⁸⁹Zr]Zr-Df-IgG1 (1 mg/kg, 4.6 MBq) were assessed in human VISTA knock-in female (C57BL/6 N-Vsir^{tm1.1(VSIR)Geno}, huVISTA KI) or control C57BL/6 mice bearing syngeneic MB49 bladder cancer tumours; and in BALB/c nu/nu mice bearing pancreatic Capan-2 tumours.</p><p><strong>Results: </strong>Stable constructs with an average chelator-to-antibody ratio of 1.81 were achieved. SDS-PAGE and SE-HPLC showed integrity of CI-8993 was maintained after conjugation; and ELISA indicated no impact of conjugation and radiolabelling on binding to human VISTA. PET imaging and biodistribution in MB49 tumour-bearing huVISTA KI female mice showed specific localisation of [⁸⁹Zr]Zr-Df-CI-8993 to VISTA in spleen and tumour tissues expressing human VISTA. Specific tumour uptake was also demonstrated in Capan-2 xenografted BALB/c nu/nu mice.</p><p><strong>Conclusions: </strong>We radiolabelled and validated [⁸⁹Zr]Zr-Df-CI-8993 for specific binding to huVISTA in vivo. Our results demonstrate that ⁸⁹Zr-labelled CI-8993 is now suitable for targeting and imaging VISTA expression in human trials.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in coronary atherosclerotic plaque activity using ¹⁸F-sodium fluoride positron emission tomography.","authors":"Jacek Kwiecinski, Kang-Ling Wang, Evangelos Tzolos, Alastair Moss, Marwa Daghem, Philip D Adamson, Damini Dey, Patrycja Molek-Dziadosz, Dana Dawson, Parthiban Arumugam, Nikant Sabharwal, John P Greenwood, John N Townend, Patrick A Calvert, James Hf Rudd, Daniel Berman, Johan W Verjans, Michelle C Williams, Piotr Slomka, Marc R Dweck, David E Newby","doi":"10.1007/s00259-024-06810-x","DOIUrl":"10.1007/s00259-024-06810-x","url":null,"abstract":"<p><strong>Introduction: </strong>There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET), and to determine whether ¹⁸F-NaF PET has prognostic value in both women and men.</p><p><strong>Methods: </strong>In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone ¹⁸F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men.</p><p><strong>Results: </strong>Baseline ¹⁸F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no ¹⁸F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p < 0.001).</p><p><strong>Conclusion: </strong>Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting tumour surface collage with hydrogel probe: a new strategy to enhance intraoperative imaging sensitivity and stability of bladder cancer.","authors":"Pengyu Guo, Ao Qi, Wenting Shang, Zehao Cai, Sheng Hu, Peng Dai, Ziyin Chen, Mingwei Sun, Zixing Wang, Zhichao Tong, Dayong Hou, Ziqi Wang, Yang Du, Jie Tian, Wanhai Xu","doi":"10.1007/s00259-024-06848-x","DOIUrl":"10.1007/s00259-024-06848-x","url":null,"abstract":"<p><strong>Purpose: </strong>The incomplete resection of non-muscle invasive bladder cancer (NMIBC) augments the risk of disease recurrence. Imaging-guided surgery by molecular probes represents a pivotal strategy for mitigating postoperative recurrence. Traditional optical molecular probes, primarily composed of antibodies/peptides targeting tumour cells and fluorescent groups, are challenged by the high heterogeneity of NMIBC cells, leading to inadequate probe sensitivity. We have developed a collagen-adhesive probe (CA-P) to target the collagen within the tumour microenvironment, aiming to address the issue of insufficient imaging sensitivity.</p><p><strong>Methods: </strong>The distribution characteristics of collagen in animal bladder cancer models and human bladder cancer tissues were explored. The synthesis and properties of CA-P were validated. In animal models, the imaging performance of CA-P was tested and compared with our previously reported near-infrared probe PLSWT7-DMI. The clinical translational potential of CA-P was assessed using human ex vivo bladder tissues.</p><p><strong>Results: </strong>The distribution of collagen on the surface of tumour cells is distinct from its expression in normal urothelium. In vitro studies have demonstrated the ability of the CA-P to undergo a \"sol-gel\" transition upon interaction with collagen. In animal models and human ex vivo bladder specimens, CA-P exhibits superior imaging performance compared to PLSWT7-DMI. The sensitivity of this probe is 94.1%, with a specificity of 81%.</p><p><strong>Conclusion: </strong>CA-P demonstrates the capability to overcome tumour cell heterogeneity and enhance imaging sensitivity, exhibiting favorable imaging outcomes in preclinical models. These findings provide a theoretical basis for the application of CA-P in intraoperative navigation for NMIBC.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PSMA radioligand therapy rechallenging: expanding the therapeutic possibilities in metastatic castration resistant prostate cancer.","authors":"Fabio Volpe, Leandra Piscopo, Michele Klain","doi":"10.1007/s00259-024-06870-z","DOIUrl":"10.1007/s00259-024-06870-z","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment to \"Targeting tumour surface collage with hydrogel probe: a new strategy to enhance intraoperative imaging sensitivity and stability of bladder cancer\".","authors":"Roberto Contieri, Alessandro Uleri, Rodolfo Hurle, Massimo Lazzeri","doi":"10.1007/s00259-024-06893-6","DOIUrl":"10.1007/s00259-024-06893-6","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-axial field-of-view PET/CT improves radiomics feature reliability.","authors":"Ian L Alberts, Song Xue, Hasan Sari, Lara Cavinato, George Prenosil, Ali Afshar-Oromieh, Clemens Mingels, Kuangyu Shi, Federico Caobelli, Arman Rahmim, Thomas Pyka, Axel Rominger","doi":"10.1007/s00259-024-06921-5","DOIUrl":"https://doi.org/10.1007/s00259-024-06921-5","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the influence of long-axial field-of-view (LAFOV) PET/CT systems on radiomics feature reliability, to assess the suitability for short-duration or low-activity acquisitions for textural feature analysis and to investigate the influence of acceptance angle.</p><p><strong>Methods: </strong>34 patients were analysed: twelve patients underwent oncological 2-[18F]-FDG PET/CT, fourteen [18F]PSMA-1007 and eight [68Ga]Ga-DOTATOC. Data were obtained using a 106 cm LAFOV system for 10 min. Sinograms were generated from list-mode data corresponding to scan durations of 2, 5, 10, 20, 30, 60, 120, 240, 360 and 600s using both standard (minimum ring difference MRD 85 crystals) and maximum acceptance angles (MRD 322). Target lesions were segmented and radiomics features were calculated. To assess feature correlation, Pearson's product-moment correlation coefficient (PPMCC) was calculated with respect to the full duration acquisition for MRD 85 and 322 respectively. The number of features with excellent (r > 0.9), moderate (r > 0.7 and < 0.9) and poor (r ≤ 0.7) correlation was compared as a measure of feature stability. Intra-class heterogeneity was assessed by means of the quartile coefficient of dispersion.</p><p><strong>Results: </strong>As expected, PPMCC improved with acquisition time for all features. By 240s almost all features showed at least moderate agreement with the full count (C100%) data, and by 360s almost all showed excellent agreement. Compared to standard-axial field of view (SAFOV) equivalent scans, fewer features showed moderate or poor agreement, and this was most pronounced for [68Ga]Ga-DOTATOC. Data obtained at C100% at MRD 322 were better able to capture between-patient heterogeneities.</p><p><strong>Conclusion: </strong>The improved feature reliability at longer acquisition times and higher MRD demonstrate the advantages of high sensitivity LAFOV systems for reproducible and low-noise data. High fidelity between MRD 85 and MRD 322 was seen at all scan durations > 2s. When contrasted with data comparable to a simulated SAFOV acquisition, full-count and full-MRD data were better able to capture underlying feature heterogeneities.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individual-level metabolic connectivity from dynamic [18F]FDG PET reveals glioma-induced impairments in brain architecture and offers novel insights beyond the SUVR clinical standard","authors":"Giulia Vallini, Erica Silvestri, Tommaso Volpi, John J. Lee, Andrei G. Vlassenko, Manu S. Goyal, Diego Cecchin, Maurizio Corbetta, Alessandra Bertoldo","doi":"10.1007/s00259-024-06956-8","DOIUrl":"https://doi.org/10.1007/s00259-024-06956-8","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>This study evaluates the potential of within-individual Metabolic Connectivity (wi-MC), from dynamic [¹⁸F]FDG PET data, based on the Euclidean Similarity method. This approach leverages the biological information of the tracer’s full temporal dynamics, enabling the direct extraction of individual metabolic connectomes. Specifically, the proposed framework, applied to glioma pathology, seeks to assess sensitivity to metabolic dysfunctions in the whole brain, while simultaneously providing further insights into the pathophysiological mechanisms regulating glioma progression.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We designed an index (Distance from Healthy Group, <i>DfHG</i>) based on the alteration of wi-MC in each patient (<i>n</i> = 44) compared to a healthy reference (from 57 healthy controls), to individually quantify metabolic connectivity abnormalities, resulting in an Impairment Map highlighting significantly compromised areas. We then assessed whether our measure of metabolic network alteration is associated with well-established markers of disease severity (tumor grade and volume, with and without edema). Subsequently, we investigated disruptions in wi-MC homotopic connectivity, assessing both affected and seemingly healthy tissue to deepen the pathology’s impact on neural communication. Finally, we compared network impairments with local metabolic alterations determined from SUVR, a validated diagnostic tool in clinical practice.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Our framework revealed how gliomas cause extensive alterations in the topography of brain networks, even in structurally unaffected regions outside the lesion area, with a significant reduction in connectivity between contralateral homologous regions. High-grade gliomas have a stronger impact on brain networks, and edema plays a mediating role in global metabolic alterations. As compared to the conventional SUVR-based analysis, our approach offers a more holistic view of the disease burden in individual patients, providing interesting additional insights into glioma-related alterations.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Considering our results, individual PET connectivity estimates could hold significant clinical value, potentially allowing the identification of new prognostic factors and personalized treatment in gliomas or other focal pathologies.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear imaging of PD-L1 expression promotes the synergistic antitumor efficacy of targeted radionuclide therapy and immune checkpoint blockade","authors":"Jiyun Shi, Hannan Gao, Yue Wu, Chuangwei Luo, Guangjie Yang, Qi Luo, Bing Jia, Chuanhui Han, Zhaofei Liu, Fan Wang","doi":"10.1007/s00259-024-06962-w","DOIUrl":"https://doi.org/10.1007/s00259-024-06962-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>In order to maximize synergistic effect of targeted radionuclide therapy (TRT) and immune checkpoint blockade (ICB) as well as reduce the toxicity, we pioneered a strategy guided by PD-L1-targeted nuclear medicine imaging for the combination of TRT and ICB towards precision cancer therapy.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>As a novel targeted radiotherapeutic agent, ¹⁷⁷Lu-AB-3PRGD₂ targeting integrin α_vβ₃ was developed to achieve sustained antitumor effect by introducing an albumin binder (AB) into the structure of 3PRGD₂. The ¹⁷⁷Lu-AB-3PRGD₂ TRT as well as different types of combination therapies of ¹⁷⁷Lu-AB-3PRGD₂ TRT and anti-PD-L1 ICB were performed in animal models. The changes of PD-L1 expression in tumors after TRT were evaluated in vitro and in vivo by PD-L1-specific SPECT/CT imaging of ^99mTc-MY1523.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>¹⁷⁷Lu-AB-3PRGD₂ showed improved tumor uptake and prolonged tumor retention, leading to significantly enhanced tumor growth suppression. Moreover, ¹⁷⁷Lu-AB-3PRGD₂ TRT remodeled the tumor immune microenvironment by upregulating PD-L1 expression and increasing tumor-infiltrating CD8⁺ T cells, facilitating immunotherapy. We found that the anti-PD-L1 treatment was more effective during the upregulation of tumor PD-L1 expression, and the time window could be determined by ^99mTc-MY1523 SPECT/CT.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>We developed a novel and long-acting radiotherapeutic agent ¹⁷⁷Lu-AB-3PRGD₂, and pioneered a strategy guided by PD-L1-targeted nuclear medicine imaging for the combination of TRT and ICB towards precision cancer therapy, optimizing the therapeutic efficacy and reducing the cost and potential toxicity risks. This strategy could also be adapted for clinical practice, combining conventional radiotherapy or chemotherapy with ICB to enhance therapeutic efficacy.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Holmium-166 radioembolisation dosimetry in HCC","authors":"Margot T. M. Reinders, Arthur J. A. T. Braat, Karel J. van Erpecum, Joep de Bruijne, Rutger C. G. Bruijnen, Dave Sprengers, Rob de Man, Erik Vegt, Jan N. M. IJzermans, Sjoerd G. Elias, Marnix G. E. H. Lam, Maarten L. J. Smits","doi":"10.1007/s00259-024-06940-2","DOIUrl":"https://doi.org/10.1007/s00259-024-06940-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>To evaluate dosimetry, dose–response and dose-toxicity relationships for holmium-166 (¹⁶⁶Ho) radioembolisation in patients with hepatocellular carcinoma (HCC).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Thirty-one patients with hepatocellular carcinoma were included in the HEPAR Primary study (NCT03379844, registered on December 20th, 2017) and underwent ¹⁶⁶Ho-microspheres radioembolisation. Linear mixed models assessed the association between tumour absorbed doses and response based on mRECIST both on tumour and patient level. Preliminary tumour absorbed dose thresholds were estimated based on predictive value. Linear regression models assessed the association between non-tumour absorbed dose and Common Terminology Criteria for Adverse Events version 4.03.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Median tumour absorbed dose (tumour level) was 95.5 Gy (range 44—332 Gy). Median non-tumour absorbed dose based on whole liver volume was 19 Gy (range 3 – 48 Gy) and based on target liver volume was 30 Gy (range 13 – 54 Gy). There was a significant association between non-tumour absorbed dose and toxicity. Tumours with partial response/complete response (PR/CR, responders) received a 41% higher absorbed dose than tumours with progressive disease/stable disease (PD/SD, non-responders) (95%CI: 2%-93%, <i>p</i> = 0.04). A predictive value of 90% for tumour response was observed at a tumour absorbed dose threshold of 155 Gy, 100% predictive value was achieved at 184.5 Gy.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This study confirms a positive relationship between tumour absorbed dose and response and between non-tumour absorbed dose and toxicity. Dose thresholds found in this study can serve as a basis for personalized dosimetry in HCC patients treated with ¹⁶⁶Ho-microspheres.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}