European Journal of Nuclear Medicine and Molecular Imaging最新文献

{"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":"https://doi.org/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":"2024-07-26","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":"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":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the tolerability of ¹⁶¹Tb- and ¹⁷⁷Lu-labeled somatostatin analogues in the preclinical setting.","authors":"Sarah D Busslinger, Ana Katrina Mapanao, Kristel Kegler, Peter Bernhardt, Fabienne Flühmann, Julia Fricke, Jan Rijn Zeevaart, Ulli Köster, Nicholas P van der Meulen, Roger Schibli, Cristina Müller","doi":"10.1007/s00259-024-06827-2","DOIUrl":"https://doi.org/10.1007/s00259-024-06827-2","url":null,"abstract":"<p><strong>Purpose: </strong>[¹⁷⁷Lu]Lu-DOTATATE is an established somatostatin receptor (SSTR) agonist for the treatment of metastasized neuroendocrine neoplasms, while the SSTR antagonist [¹⁷⁷Lu]Lu-DOTA-LM3 has only scarcely been employed in clinics. Impressive preclinical data obtained with [¹⁶¹Tb]Tb-DOTA-LM3 in tumor-bearing mice indicated the potential of terbium-161 as an alternative to lutetium-177. The aim of the present study was to compare the tolerability of ¹⁶¹Tb- and ¹⁷⁷Lu-based DOTA-LM3 and DOTATATE in immunocompetent mice.</p><p><strong>Methods: </strong>Dosimetry calculations were performed based on biodistribution data of the radiopeptides in immunocompetent mice. Treatment-related effects on blood cell counts were assessed on Days 10, 28 and 56 after application of [¹⁶¹Tb]Tb-DOTA-LM3 or [¹⁶¹Tb]Tb-DOTATATE at 20 MBq per mouse. These radiopeptides were also applied at 100 MBq per mouse and the effects compared to those observed after application of the ¹⁷⁷Lu-labeled counterparts. Bone marrow smears, blood plasma parameters and organ histology were assessed at the end of the study.</p><p><strong>Results: </strong>The absorbed organ dose was commonly higher for the SSTR antagonist than for the SSTR agonist and for terbium-161 over lutetium-177. Application of a therapeutic activity level of 20 MBq [¹⁶¹Tb]Tb-DOTA-LM3 or [¹⁶¹Tb]Tb-DOTATATE was well tolerated without major hematological changes. The injection of 100 MBq of the ¹⁶¹Tb- and ¹⁷⁷Lu-based somatostatin analogues affected the blood cell counts, however. The lymphocytes were 40-50% lower in treated mice compared to the untreated controls on Day 10 irrespective of the radionuclide employed. At the same timepoint, thrombocyte and erythrocyte counts were 30-50% and 6-12% lower, respectively, after administration of the SSTR antagonist (p < 0.05) while changes were less pronounced in mice injected with the SSTR agonist. All blood cell counts were in the normal range on Day 56. Histological analyses revealed minimal abnormalities in the kidneys, liver and spleen of treated mice. No correlation was observed between the organ dose and frequency of the occurrence of abnormalities.</p><p><strong>Conclusion: </strong>Hematologic changes were more pronounced in mice treated with the SSTR antagonist than in those treated with the SSTR agonist. Despite the increased absorbed dose delivered by terbium-161 over lutetium-177, [¹⁶¹Tb]Tb-DOTA-LM3 and [¹⁶¹Tb]Tb-DOTATATE should be safe at activity levels that are recommended for their respective ¹⁷⁷Lu-based analogues.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751435","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":"The first-in-human preclinical evaluation of the new probe [123I]I-PSMA-7 for real-time intraoperative targeted biopsy and SPECT/CT imaging in prostate cancer.","authors":"Xiaohui Luan, Shaoxi Niu, Yachao Liu, Xiaojun Zhang, Xiaodan Xu, Shuwei Sun, Yabing Sun, Jingfeng Zhang, Yuan Wang, Zhiqiang Chen, Yimin Chen, Mengchao Cui, Ruimin Wang, Xu Zhang, Jinming Zhang, Baixuan Xu","doi":"10.1007/s00259-024-06833-4","DOIUrl":"https://doi.org/10.1007/s00259-024-06833-4","url":null,"abstract":"<p><strong>Purpose: </strong>PSMA/PET has been increasingly used to detect PCa, and PSMA/PET-guided biopsy has shown promising results. However, it cannot be confirmed immediately whether the tissues are the targeted area. In this study, we aimed to develop a novel probe, [¹²³I]I-PSMA-7. First, we hope that [¹²³I]I-PSMA-7 can provide instant confirmation for prostate biopsy. Second, we hope it will help detect PCa.</p><p><strong>Methods: </strong>We synthesized a high-affinity probe, [¹²³I]I-PSMA-7, and evaluated its properties. We included ten patients with suspected PCa and divided them into two groups. The injection and biopsy were approximately 24 h apart. The activity in biopsy lesions was measured as the cpm by a γ-counter. Moreover, we enrolled 3 patients to evaluate the potential of [¹²³I]I-PSMA-7 for detecting PCa.</p><p><strong>Results: </strong>Animal experiments verified the safety, targeting and effectiveness of [¹²³I]I-PSMA-7, and the tumor-to-muscle ratio was greatest at 24 h, which confirmed the results of this study in humans. After injection of 185MBq [¹²³I]I-PSMA-7, 18/55 cores were positive, and the cpm was significantly greater (4345 ± 3547 vs. 714 ± 547, P < 0.001), with an AUC of 0.97 and a cutoff of 1312 (sens/spec of 94.40%/91.90%). At a lower dose, 10/55 biopsy cores were cancerous, and the cpm was 2446 ± 1622 vs. 153 ± 112 (P < 0.001). The AUC was 1, with a cutoff value of 490 (sens/spec of 100%). When the radiopharmaceuticals were added to 370 MBq, we achieved better SPECT/CT imaging.</p><p><strong>Conclusion: </strong>With the aid of [¹²³I]I-PSMA-7 and via cpm-based biopsy, we can reduce the number of biopsies to a minimum operation. [¹²³I]I-PSMA-7 PSMA SPECT/CT can also provide good imaging results.</p><p><strong>Trial registration: </strong>Chinese Clinical trial registry ChiCTR2300069745, Registered 24 March 2023.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747759","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":"IE-CycleGAN: improved cycle consistent adversarial network for unpaired PET image enhancement.","authors":"Jianan Cui, Yi Luo, Donghe Chen, Kuangyu Shi, Xinhui Su, Huafeng Liu","doi":"10.1007/s00259-024-06823-6","DOIUrl":"https://doi.org/10.1007/s00259-024-06823-6","url":null,"abstract":"<p><strong>Purpose: </strong>Technological advances in instruments have greatly promoted the development of positron emission tomography (PET) scanners. State-of-the-art PET scanners such as uEXPLORER can collect PET images of significantly higher quality. However, these scanners are not currently available in most local hospitals due to the high cost of manufacturing and maintenance. Our study aims to convert low-quality PET images acquired by common PET scanners into images of comparable quality to those obtained by state-of-the-art scanners without the need for paired low- and high-quality PET images.</p><p><strong>Methods: </strong>In this paper, we proposed an improved CycleGAN (IE-CycleGAN) model for unpaired PET image enhancement. The proposed method is based on CycleGAN, and the correlation coefficient loss and patient-specific prior loss were added to constrain the structure of the generated images. Furthermore, we defined a normalX-to-advanced training strategy to enhance the generalization ability of the network. The proposed method was validated on unpaired uEXPLORER datasets and Biograph Vision local hospital datasets.</p><p><strong>Results: </strong>For the uEXPLORER dataset, the proposed method achieved better results than non-local mean filtering (NLM), block-matching and 3D filtering (BM3D), and deep image prior (DIP), which are comparable to Unet (supervised) and CycleGAN (supervised). For the Biograph Vision local hospital datasets, the proposed method achieved higher contrast-to-noise ratios (CNR) and tumor-to-background SUVmax ratios (TBR) than NLM, BM3D, and DIP. In addition, the proposed method showed higher contrast, SUV_max, and TBR than Unet (supervised) and CycleGAN (supervised) when applied to images from different scanners.</p><p><strong>Conclusion: </strong>The proposed unpaired PET image enhancement method outperforms NLM, BM3D, and DIP. Moreover, it performs better than the Unet (supervised) and CycleGAN (supervised) when implemented on local hospital datasets, which demonstrates its excellent generalization ability.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747758","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":"Pulmonary embolism as an incidental finding in [¹⁵O]H₂O PET/CT myocardial perfusion imaging.","authors":"Julie Loft Nagel, Lars Poulsen Tolbod, Hendrik Johannes Harms, Lars Christian Gormsen, Michael Alle Madsen","doi":"10.1007/s00259-024-06849-w","DOIUrl":"https://doi.org/10.1007/s00259-024-06849-w","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733762","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":"⁶⁸Ga-Trivehexin PET/CT: a promising novel tracer for primary hyperparathyroidism.","authors":"Serkan Kuyumcu, Dilara Denizmen, Duygu Has-Simsek, Arzu Poyanli, Ayşe Kubat Uzum, Fikret Buyukkaya, Emine Goknur Isik, Semen Onder, Nihat Aksakal, Zeynep Gozde Ozkan, Yasemin Sanli","doi":"10.1007/s00259-024-06846-z","DOIUrl":"https://doi.org/10.1007/s00259-024-06846-z","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to assess ⁶⁸Ga-Trivehexin PET/CT for detecting hyperfunctioning parathyroid tissue in comparison to [^99mTc]Tc-MIBI scintigraphy-SPECT/CT (MIBI scan) in patients with primary hyperparathyroidism (PHPT).</p><p><strong>Methods: </strong>The cohort comprised 13 patients diagnosed with PHPT based on biochemical analyses, including serum calcium, phosphorus, and parathyroid hormone (PTH) levels. Each participant underwent cervical ultrasonography, MIBI scan, and ⁶⁸Ga-Trivehexin PET/CT imaging. Complementary 4D-CT and [¹⁸F]fluorocholine PET/CT were conducted in 7 patients. Ten lesions of 7 patients underwent PTH wash-out (WO) procedure. ⁶⁸Ga-Trivehexin PET/CT findings were compared with other modalities and PTH-WO results.</p><p><strong>Results: </strong>Ten patients had sporadic PHPT, while 3 were diagnosed with MEN-1 syndrome-associated PHPT. One patient did not have any identifiable parathyroid lesion across the imaging modalities. On a patient-based analysis, MIBI scan and ⁶⁸Ga-Trivehexin PET/CT identified parathyroid lesions in 10 and 11 patients, respectively. However, ⁶⁸Ga-Trivehexin PET/CT detected 7 additional parathyroid lesions that were negative on the MIBI scan. Consequently, 17 lesions were identified and confirmed as hyperfunctioning parathyroid tissue through imaging, PTH-WO, or a combination of both modalities. In lesion-based evaluation, ⁶⁸Ga-Trivehexin identified 16 lesions compared to 10 by MIBI scan, resulting in a detection rate of 94.1% and 58.8%, respectively. Notably, in three patients who underwent [¹⁸F]fluorocholine PET/CT, no lesions were detected; yet ⁶⁸Ga-Trivehexin PET/CT successfully identified parathyroid lesions in two of these patients.</p><p><strong>Conclusion: </strong>Our study provides the first evidence that ⁶⁸Ga-Trivehexin PET/CT can effectively identify hyperfunctioning parathyroid tissue with a high detection rate warranting further investigations to comprehensively explore its potential in PHPT management.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723306","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":"Combining [¹⁷⁷Lu]Lu-DOTA-TOC PRRT with PARP inhibitors to enhance treatment efficacy in small cell lung cancer.","authors":"Hartmut Rauch, Carolin Kitzberger, Kirti Janghu, Pavithra Hawarihewa, Nghia T Nguyen, Yu Min, Simone Ballke, Katja Steiger, Wolfgang A Weber, Susanne Kossatz","doi":"10.1007/s00259-024-06844-1","DOIUrl":"10.1007/s00259-024-06844-1","url":null,"abstract":"<p><strong>Purpose: </strong>Small cell lung cancer (SCLC) is a highly aggressive tumor with neuroendocrine origin. Although SCLC frequently express somatostatin receptor type 2 (SSTR2), a significant clinical benefit of SSTR2-targeted radionuclide therapies of SCLC was not observed so far. We hypothesize that combination treatment with a PARP inhibitor (PARPi) could lead to radiosensitization and increase the effectiveness of SSTR2-targeted therapy in SCLC.</p><p><strong>Methods: </strong>SSTR2-ligand uptake of the SCLC cell lines H69 and H446 was evaluated in vitro using flow cytometry, and in vivo using SPECT imaging and cut-and-count biodistribution. Single-agent (Olaparib, Rucaparib, [¹⁷⁷Lu]Lu-DOTA-TOC) and combination treatment responses were determined in vitro via cell viability, clonogenic survival and γH2AX DNA damage assays. In vivo, we treated athymic nude mice bearing H69 or H446 xenografts with Olaparib, Rucaparib, or [¹⁷⁷Lu]Lu-DOTA-TOC alone or with combination treatment regimens to assess the impact on tumor growth and survival of the treated mice.</p><p><strong>Results: </strong>H446 and H69 cells exhibited low SSTR2 expression, i.e. 60 to 90% lower uptake of SSTR2-ligands compared to AR42J cells. In vitro, combination treatment of [¹⁷⁷Lu]Lu-DOTA-TOC with PARPi resulted in 2.9- to 67-fold increased potency relative to [¹⁷⁷Lu]Lu-DOTA-TOC alone. We observed decreased clonogenic survival and higher amounts of persistent DNA damage compared to single-agent treatment for both Olaparib and Rucaparib. In vivo, tumor doubling times increased to 1.6-fold (H446) and 2.2-fold (H69) under combination treatment, and 1.0 to 1.1-fold (H446) and 1.1 to 1.7-fold (H69) in monotherapies compared to untreated animals. Concurrently, median survival was higher in the combination treatment groups in both models compared to monotherapy and untreated mice. Fractionating the PRRT dose did not lead to further improvement of therapeutic outcome.</p><p><strong>Conclusion: </strong>The addition of PARPi can markedly improve the potency of SSTR2-targeted PRRT in SCLC models in SSTR2 low-expressing tumors. Further evaluation in humans seems justified based on the results as novel treatment options for SCLC are urgently needed.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633018","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":"Correction to: EANM perspectives for CZT SPECT in brain applications.","authors":"Antoine Verger, Diego Cecchin, Eric Guedj, Nathalie L Albert, Matthias Brendel, Francesco Fraioli, Nelleke Tolboom, Tatjana Traub-Weidinger, Igor Yakushev, Donatienne Van Weehaeghe, Pablo Aguiar Fernandez, Valentina Garibotto, Laetitia Imbert","doi":"10.1007/s00259-024-06842-3","DOIUrl":"https://doi.org/10.1007/s00259-024-06842-3","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626378","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":"Quinazoline-2,4(1 H,3 H)-dione Scaffold for development of a novel PARP-targeting PET probe for tumor imaging.","authors":"Chunfeng He, Hui Shi, Boyu Tan, Zhaoning Jiang, Rui Cao, Jiamin Zhu, Kun Qian, Xiao Wang, Xiaoping Xu, Chunrong Qu, Shaoli Song, Zhen Cheng","doi":"10.1007/s00259-024-06843-2","DOIUrl":"https://doi.org/10.1007/s00259-024-06843-2","url":null,"abstract":"<p><strong>Purpose: </strong>Overexpression of Poly (ADP-ribose) polymerase (PARP) is associated with many diseases such as oncological diseases. Several PARP-targeting radiotracers have been developed to detect tumor in recent years. Two ¹⁸F labelled probes based on Olaparib and Rucaparib molecular scaffolds have been evaluated in clinical trials, but their slow hepatic clearance hinders their tumor imaging performance. Although a number of positron emission tomography (PET) probes with lower liver uptake have been designed, the tumor to background ratios remains to be low. Therefore, we designed a probe with low lipid-water partition coefficient to solve this problem.</p><p><strong>Methods: </strong>A pyridine-containing quinazoline-2,4(1 H,3 H)-dione PARP-targeting group was rationally designed and used to conjugate with the chelator 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) to prepare the lead compound named as SMIC-2001 for radiolabeling. In vitro experiments, the lipid-water partition coefficient, stability, binding affinity, and cellular uptake of [⁶⁸Ga]Ga-SMIC-2001 were determined. In vivo experiments, the U87MG xenograft models were used to evaluate its tumor imaging properties.</p><p><strong>Results: </strong>[⁶⁸Ga]Ga-SMIC-2001 showed a low Log D_7.4 (-3.82 ± 0.06) and high affinity for PARP-1 (48.13 nM). In vivo study revealed that it exhibited a high tumor-to-background contrast in the U87MG xenograft models and mainly renal clearance. And the ratios of tumor to main organs were high except for the kidney (e.g. tumor to liver ratio reached 2.20 ± 0.51) at 60 min p.i.</p><p><strong>Conclusion: </strong>In summary, pyridine-containing quinazoline-2,4(1 H,3 H)-dione is a novel PARP-targeting molecular scaffold for imaging probe development, and [⁶⁸Ga]Ga-SMIC-2001 is a highly promising PET probe capable of imaging tumors with PARP overexpression.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619693","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}