European Journal of Nuclear Medicine and Molecular Imaging最新文献

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Preclinical evaluation of the novel [18F]CHDI-650 PET ligand for non-invasive quantification of mutant huntingtin aggregates in Huntington's disease. 新型[18F]CHDI-650 PET 配体用于亨廷顿氏病突变亨廷丁聚合体无创量化的临床前评估。
IF 8.6 1区 医学
European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2024-08-27 DOI: 10.1007/s00259-024-06880-x
Franziska Zajicek, Jeroen Verhaeghe, Stef De Lombaerde, Annemie Van Eetveldt, Alan Miranda, Ignacio Munoz-Sanjuan, Celia Dominguez, Vinod Khetarpal, Jonathan Bard, Longbin Liu, Steven Staelens, Daniele Bertoglio
{"title":"Preclinical evaluation of the novel [<sup>18</sup>F]CHDI-650 PET ligand for non-invasive quantification of mutant huntingtin aggregates in Huntington's disease.","authors":"Franziska Zajicek, Jeroen Verhaeghe, Stef De Lombaerde, Annemie Van Eetveldt, Alan Miranda, Ignacio Munoz-Sanjuan, Celia Dominguez, Vinod Khetarpal, Jonathan Bard, Longbin Liu, Steven Staelens, Daniele Bertoglio","doi":"10.1007/s00259-024-06880-x","DOIUrl":"https://doi.org/10.1007/s00259-024-06880-x","url":null,"abstract":"<p><strong>Purpose: </strong>Positron emission tomography (PET) imaging of mutant huntingtin (mHTT) aggregates is a potential tool to monitor disease progression as well as the efficacy of candidate therapeutic interventions for Huntington's disease (HD). To date, the focus has been mainly on the investigation of <sup>11</sup>C radioligands; however, favourable <sup>18</sup>F radiotracers will facilitate future clinical translation. This work aimed at characterising the novel [<sup>18</sup>F]CHDI-650 PET radiotracer using a combination of in vivo and in vitro approaches in a mouse model of HD.</p><p><strong>Methods: </strong>After characterising [<sup>18</sup>F]CHDI-650 using in vitro autoradiography, we assessed in vivo plasma and brain radiotracer stability as well as kinetics through dynamic PET imaging in the heterozygous (HET) zQ175DN mouse model of HD and wild-type (WT) littermates at 9 months of age. Additionally, we performed a head-to-head comparison study at 3 months with the previously published [<sup>11</sup>C]CHDI-180R radioligand.</p><p><strong>Results: </strong>Plasma and brain radiometabolite profiles indicated a suitable metabolic profile for in vivo imaging of [<sup>18</sup>F]CHDI-650. Both in vitro autoradiography and in vivo [<sup>18</sup>F]CHDI-650 PET imaging at 9 months of age demonstrated a significant genotype effect (p < 0.0001) despite the poor test-retest reliability. [<sup>18</sup>F]CHDI-650 PET imaging at 3 months of age displayed higher differentiation between genotypes when compared to [<sup>11</sup>C]CHDI-180R.</p><p><strong>Conclusion: </strong>Overall, [<sup>18</sup>F]CHDI-650 allows for discrimination between HET and WT zQ175DN mice at 9 and 3 months of age. [<sup>18</sup>F]CHDI-650 represents the first suitable <sup>18</sup>F radioligand to image mHTT aggregates in mice and its clinical evaluation is underway.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072371","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}
引用次数: 0
[177Lu]Lu DOTATOC PRRT with PARP inhibitors in small cell lung cancer. 小细胞肺癌中的[177Lu]Lu DOTATOC PRRT 与 PARP 抑制剂。
IF 8.6 1区 医学
European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2024-08-27 DOI: 10.1007/s00259-024-06892-7
Leandra Piscopo, Salvatore Masala, Mariano Scaglione, Michele Klain
{"title":"[<sup>177</sup>Lu]Lu DOTATOC PRRT with PARP inhibitors in small cell lung cancer.","authors":"Leandra Piscopo, Salvatore Masala, Mariano Scaglione, Michele Klain","doi":"10.1007/s00259-024-06892-7","DOIUrl":"https://doi.org/10.1007/s00259-024-06892-7","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072370","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}
引用次数: 0
Correction to: Targeting of immune checkpoint regulator V-domain Ig suppressor of T-cell activation (VISTA) with 89Zr-labelled CI-8993. 更正:用89Zr标记的CI-8993靶向免疫检查点调节因子V-domain Ig抑制T细胞活化(VISTA)。
IF 8.6 1区 医学
European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2024-08-26 DOI: 10.1007/s00259-024-06869-6
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, Ingrid Julienne, Georgette Burvenich
{"title":"Correction to: Targeting of immune checkpoint regulator V-domain Ig suppressor of T-cell activation (VISTA) with <sup>89</sup>Zr-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, Ingrid Julienne, Georgette Burvenich","doi":"10.1007/s00259-024-06869-6","DOIUrl":"https://doi.org/10.1007/s00259-024-06869-6","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055261","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}
引用次数: 0
Enhanced detection of damaged myocardium and risk stratification in hypertrophic cardiomyopathy using integrated [68Ga]Ga-FAPI-04 PET/CMR imaging 利用[68Ga]Ga-FAPI-04 PET/CMR综合成像增强肥厚型心肌病受损心肌的检测和风险分层能力
IF 9.1 1区 医学
European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2024-08-24 DOI: 10.1007/s00259-024-06878-5
Jie Ding, Hang Zhang, Xing Chen, Haiyan Wang, Weilun Wang, Zhiwen You, Liming Gao, Qi Zhang, Jun Zhao
{"title":"Enhanced detection of damaged myocardium and risk stratification in hypertrophic cardiomyopathy using integrated [68Ga]Ga-FAPI-04 PET/CMR imaging","authors":"Jie Ding, Hang Zhang, Xing Chen, Haiyan Wang, Weilun Wang, Zhiwen You, Liming Gao, Qi Zhang, Jun Zhao","doi":"10.1007/s00259-024-06878-5","DOIUrl":"https://doi.org/10.1007/s00259-024-06878-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>This study aims to explore the correlation between PET and CMR in integrated [<sup>68</sup>Ga]Ga-FAPI-04 PET/CMR multimodal imaging and its value in the diagnosis and risk assessment of hypertrophic cardiomyopathy (HCM).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This study included 20 HCM patients and 11 age- and gender-matched controls. PET analysis evaluated left ventricular (LV) [<sup>68</sup>Ga]Ga-FAPI-04 uptake, including SUV<sub>max</sub>, TBR, cardiac fibroblast activity (CFA) and volume (CFV), and total SUV of the 16 segments. CMR tissue characterization parameters included cardiac function, myocardial thickness, late gadolinium enhancement (LGE), relaxation time, extracellular volume (ECV), and peak strain parameters. The 5-year sudden cardiac death (SCD) risk score and the 2-year and 5-year atrial fibrillation (AF) risk scores were calculated for each patient. The study analyzed differences between HCM patients and controls, the correlation between [<sup>68</sup>Ga]Ga-FAPI-04 PET and concurrent CMR imaging results, and the predictive value of PET/CMR.</p><h3 data-test=\"abstract-sub-heading\">Result</h3><p>The FAPI uptake, myocardial mass, myocardial thickness, and T1/T2 mapping values were significantly higher in HCM patients compared to controls. Twenty HCM patients and their 320 myocardial segments were discussed. Increased [<sup>68</sup>Ga]Ga-FAPI-04 uptake in the left ventricular wall was observed in 95% (19/20) of the patients, covering 48.8% (156/320) of the segments. On concurrent CMR, 80% (16/20) of the patients showed LGE, including 95 (29.7%) segments. The FAPI(+)LGE(+) segments exhibited the highest myocardial PET uptake, greatest thickness, longest T1/T2 native values, largest ECV value and the greatest loss of myocardial strain capacity (<i>P</i> &lt; 0.05). There was a significant correlation between FAPI uptake and CMR parameters (<i>P</i> &lt; 0.05). Higher [<sup>68</sup>Ga]Ga-FAPI-04 uptake showed a positive correlation with SCD and AF risk scores (<i>P</i> &lt; 0.05). The number of LGE(+) segments, mapping parameters, and ECV values in CMR also had prognostic significance. Combining PET with CMR aided in further risk stratification of HCM.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>[<sup>68</sup>Ga]Ga-FAPI-04 PET/CMR multimodal imaging has potential value in the detection of damaged myocardial lesions and risk assessment of HCM patients. [<sup>68</sup>Ga]Ga-FAPI-04 PET can detect more affected myocardium compared to CMR, and segments with abnormalities in both PET and CMR show more severe myocardial damage.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142045636","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}
引用次数: 0
Correction to: B-Glycine as a marker for β cell imaging and β cell mass evaluation. 更正:B-甘氨酸作为β细胞成像和β细胞质量评估的标记物。
IF 8.6 1区 医学
European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2024-08-23 DOI: 10.1007/s00259-024-06884-7
Yuxiang Han, Hui Liu, Yimin Li, Zhibo Liu
{"title":"Correction to: B-Glycine as a marker for β cell imaging and β cell mass evaluation.","authors":"Yuxiang Han, Hui Liu, Yimin Li, Zhibo Liu","doi":"10.1007/s00259-024-06884-7","DOIUrl":"https://doi.org/10.1007/s00259-024-06884-7","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035505","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}
引用次数: 0
[18F]AlF-CBP imaging of type I collagen for non-invasive monitoring of pulmonary fibrosis in preclinical models. I 型胶原的[18F]AlF-CBP 成像用于临床前模型肺纤维化的无创监测。
IF 8.6 1区 医学
European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2024-08-22 DOI: 10.1007/s00259-024-06888-3
Yang Liu, Peipei Tang, Simin Peng, Jinmei Zhong, Zexin Xu, Jiawei Zhong, Jin Su, Yuhua Zhong, Kongzhen Hu
{"title":"[<sup>18</sup>F]AlF-CBP imaging of type I collagen for non-invasive monitoring of pulmonary fibrosis in preclinical models.","authors":"Yang Liu, Peipei Tang, Simin Peng, Jinmei Zhong, Zexin Xu, Jiawei Zhong, Jin Su, Yuhua Zhong, Kongzhen Hu","doi":"10.1007/s00259-024-06888-3","DOIUrl":"https://doi.org/10.1007/s00259-024-06888-3","url":null,"abstract":"<p><strong>Purpose: </strong>Pulmonary fibrosis is an irreversible scar-forming condition for which there is a lack of non-invasive and specific methods for monitoring its progression and therapy efficacy. However, the disease is known to be accompanied by collagen accumulation. Here, we developed a novel positron emission tomography (PET) probe targeting type I collagen to evaluate its utility for the non-invasive assessment of pulmonary fibrosis.</p><p><strong>Methods: </strong>We designed a <sup>18</sup>F-labeled PET probe ([<sup>18</sup>F]AlF-CBP) to target type I collagen and evaluated its binding affinity, specificity and stability in vitro. PET with [<sup>18</sup>F]AlF-CBP, CT, histopathology, immunofluorescence, and biochemical indice were performed to assess and quantify type I collagen levels and pulmonary fibrosis progression and treatment in murine models. Dynamic PET/CT studies of [<sup>18</sup>F]AlF-CBP were conducted to assess lung fibrosis in non-human primate models.</p><p><strong>Results: </strong>[<sup>18</sup>F]AlF-CBP was successfully prepared, and in vitro and in vivo tests showed high stability (> 95%) and type I collagen specificity (IC<sub>50</sub> = 0.36 µM). The lungs of the fibrotic murine model showed more elevated probe uptake and retention compared to the control group, and there was a positive correlation between the radioactivity uptake signals and the degree of fibrosis (CT: R<sup>2</sup> = 0.89, P < 0.0001; hydroxyproline levels: R<sup>2</sup> = 0.89, P < 0.0001). PET signals also correlated well with mean lung density in non-human primate models of pulmonary fibrosis (R<sup>2</sup> = 0.84, P < 0.0001).</p><p><strong>Conclusion: </strong>[<sup>18</sup>F]AlF-CBP PET imaging is a promising non-invasive method for specific monitoring of lung fibrosis progression and therapy efficacy.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016710","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}
引用次数: 0
May the Nuclear Medicine be with you! Neuroendocrine tumours and the return of nuclear medicine. 愿核医学与你同在神经内分泌肿瘤与核医学的回归。
IF 8.6 1区 医学
European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2024-08-19 DOI: 10.1007/s00259-024-06877-6
Ozgul Ekmekcioglu, Simon Hughes, Wolfgang P Fendler, Fred Verzijlbergen, Grace Kong, Michael S Hofman
{"title":"May the Nuclear Medicine be with you! Neuroendocrine tumours and the return of nuclear medicine.","authors":"Ozgul Ekmekcioglu, Simon Hughes, Wolfgang P Fendler, Fred Verzijlbergen, Grace Kong, Michael S Hofman","doi":"10.1007/s00259-024-06877-6","DOIUrl":"https://doi.org/10.1007/s00259-024-06877-6","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999613","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}
引用次数: 0
Noninvasive quantification of [18F]SynVesT-1 binding using simplified reference tissue model 2. 使用简化参考组织模型 2 对[18F]SynVesT-1 结合进行无创量化。
IF 8.6 1区 医学
European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2024-08-19 DOI: 10.1007/s00259-024-06885-6
Mika Naganawa, Jean-Dominique Gallezot, Songye Li, Nabeel B Nabulsi, Shannan Henry, Zhengxin Cai, David Matuskey, Yiyun Huang, Richard E Carson
{"title":"Noninvasive quantification of [<sup>18</sup>F]SynVesT-1 binding using simplified reference tissue model 2.","authors":"Mika Naganawa, Jean-Dominique Gallezot, Songye Li, Nabeel B Nabulsi, Shannan Henry, Zhengxin Cai, David Matuskey, Yiyun Huang, Richard E Carson","doi":"10.1007/s00259-024-06885-6","DOIUrl":"10.1007/s00259-024-06885-6","url":null,"abstract":"<p><strong>Purpose: </strong>[<sup>18</sup>F]SynVesT-1, a positron emission tomography (PET) radiotracer for the synaptic vesicle glycoprotein 2A (SV2A), demonstrates kinetics similar to [<sup>11</sup>C]UCB-J, with high brain uptake, fast kinetics fitting well with the one-tissue compartment (1TC) model, and excellent test-retest reproducibility. Challenges arise due to the similarity between k<sub>2</sub> and [Formula: see text] (efflux rate of the reference region), when applying the simplified reference tissue model (SRTM) and related methods in [<sup>11</sup>C]UCB-J studies to accurately estimate [Formula: see text]. This study evaluated the suitability of these methods to estimate [<sup>18</sup>F]SynVesT-1 binding using centrum semiovale (CS) or cerebellum (CER) as reference regions.</p><p><strong>Method: </strong>Seven healthy participants underwent 120-min PET scans on the HRRT scanner with [<sup>18</sup>F]SynVesT-1. Six participants underwent test and retest scans. Arterial blood sampling and metabolite analysis provided input functions for the 1TC model, serving as the gold standard for kinetic parameters values. SRTM, coupled SRTM (SRTMC) and SRTM2 estimated were applied to estimate [Formula: see text](ref: CS) and DVR<sub>CER</sub>(ref: CER) values. For SRTM2, the population average of [Formula: see text] was determined from the 1TC model applied to the reference region. Test-retest variability and minimum scan time were also calculated.</p><p><strong>Results: </strong>The 1TC k<sub>2</sub> (1/min) values for CS and CER were 0.031 ± 0.004 and 0.021 ± 0.002, respectively. Although SRTMC [Formula: see text] was much higher than 1TC [Formula: see text], SRTMC underestimated BP<sub>ND</sub>(ref: CS) and DVR<sub>CER</sub> by an average of 3% and 1% across regions, respectively, due to similar bias in k<sub>2</sub> and [Formula: see text] estimation. SRTM underestimated BP<sub>ND</sub>(ref: CS) by an average of 3%, but with the CER as reference region, SRTM estimation was unstable and DVR<sub>CER</sub> underestimation varied by region (mean 10%). Using population average [Formula: see text] values, SRTM2 BP<sub>ND</sub> and DVR<sub>CER</sub> showed the best agreement with 1TC estimates.</p><p><strong>Conclusion: </strong>Our findings support the use of population [Formula: see text] value in SRTM2 with [<sup>18</sup>F]SynVesT-1 for the estimation of [Formula: see text] or DVR<sub>CER</sub>, regardless of the choice of reference region.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999614","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}
引用次数: 0
Letter to the editor concerning 'Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis.' 致编辑的信,内容涉及 "根治性前列腺切除术后PSMA阳性结节复发患者的全盆腔与半盆腔选择性结节放疗--多机构倾向评分回顾性分析"。
IF 8.6 1区 医学
European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2024-08-19 DOI: 10.1007/s00259-024-06876-7
Aysenur Elmali, Cem Onal
{"title":"Letter to the editor concerning 'Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis.'","authors":"Aysenur Elmali, Cem Onal","doi":"10.1007/s00259-024-06876-7","DOIUrl":"https://doi.org/10.1007/s00259-024-06876-7","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999612","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}
引用次数: 0
Construction and preclinical evaluation of a 124I-labelled bispecific antibody targeting PD-L1 and PD-L2. 构建靶向 PD-L1 和 PD-L2 的 124I 标记双特异性抗体并进行临床前评估。
IF 8.6 1区 医学
European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2024-08-19 DOI: 10.1007/s00259-024-06886-5
Yuan Yao, Yanan Ren, Xingguo Hou, Pei Wang, Jinyu Zhu, Song Liu, Xiaokun Ma, Teli Liu, Zhi Yang, Hua Zhu, Nan Li
{"title":"Construction and preclinical evaluation of a <sup>124</sup>I-labelled bispecific antibody targeting PD-L1 and PD-L2.","authors":"Yuan Yao, Yanan Ren, Xingguo Hou, Pei Wang, Jinyu Zhu, Song Liu, Xiaokun Ma, Teli Liu, Zhi Yang, Hua Zhu, Nan Li","doi":"10.1007/s00259-024-06886-5","DOIUrl":"https://doi.org/10.1007/s00259-024-06886-5","url":null,"abstract":"<p><strong>Purpose: </strong>NB12 is a bispecific antibody that consists of two anti-programmed cell death-ligand 1 (PD-L1) nanobodies and two anti-programmed cell death-ligand 2 (PD-L2) nanobodies. The aim of this study was to design a novel tracer, [<sup>124</sup>I]I-NB12, targeting PD-L1/2 and perform preclinical evaluations to dynamically monitor PD-L1/2 expression for determining cancer patient responsiveness to ICI therapy.</p><p><strong>Methods: </strong>NB12 was labelled with the radionuclide <sup>124</sup>I at room temperature (RT). An in vitro binding assay was performed to assess the affinity of [<sup>124</sup>I]I-NB12 for PD-L1 and PD-L2. Cellular uptake, pharmacokinetic, and biodistribution experiments were performed to evaluate the biological properties. Micro-PET/CT imaging with [<sup>124</sup>I]I-NB12 was conducted at different time points. Immunohistochemical and haematoxylin and eosin (HE) staining experiments were carried out using tumour tissues. Routine blood, biochemical indices and major organ pathology were used to evaluate the biosafety of the tracers.</p><p><strong>Results: </strong>The radiochemical yield of [<sup>124</sup>I]I-NB12 was 84.62 ± 3.90%, and the radiochemical purity (RCP) was greater than 99%. [<sup>124</sup>I]I-NB12 had a high affinity for the PD-L1 (Kd = 19.82 nM) and PD-L2 (Kd = 2.93 nM). Cellular uptake experiments confirmed that the uptake of [<sup>124</sup>I]I-NB12 by A549-PDL1/2 cells was greater than that by A549 cells. The half-lives of the distribution phase and elimination phase were 0.26 h and 4.08 h, respectively. Micro-PET/CT showed significant [<sup>124</sup>I]I-NB12 uptake in the tumour region of A549-PDL1/2 tumour-bearing mice compared with A549 tumour-bearing mice 24 h postinjection. Immunohistochemical and HE staining experiments confirmed that tumour-bearing mice was successfully constructed.</p><p><strong>Conclusion: </strong>We constructed a bispecific antibody that targets PD-L1 and PD-L2, namely, [<sup>124</sup>I]I-NB12. Biological evaluation revealed its specificity and affinity for PD-L1/2, and micro-PET/CT confirmed the feasibility of visualizing tumour PD-L1/2 in vivo. Using [<sup>124</sup>I]I-NB12 may be a promising strategy for identifying cancer patients that can potentially benefit from ICI therapy.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999611","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}
引用次数: 0
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