European Journal of Nuclear Medicine and Molecular Imaging最新文献

{"title":"Prospective investigation of amino acid transport and PSMA-targeted positron emission tomography for metastatic lobular breast carcinoma.","authors":"Aliza Mushtaq, Ismaheel O Lawal, Saima Muzahir, Sarah C Friend, Manali Bhave, Jane L Meisel, Mylin A Torres, Toncred M Styblo, Cathy L Graham, Kevin Kalinsky, Jeffrey Switchenko, Gary Allan Ulaner, David M Schuster","doi":"10.1007/s00259-024-06830-7","DOIUrl":"10.1007/s00259-024-06830-7","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the feasibility of imaging amino-acid transport and PSMA molecular pathways in the detection of metastatic breast invasive lobular carcinoma (ILC) and if there is superior detection compared to standard-of-care imaging [computed tomography (CT)/bone scan, or ¹⁸F-FDG positron-emission-tomography (PET)-CT].</p><p><strong>Methods: </strong>20 women with de-novo or suspected metastatic ILC underwent two PET-CT scans with ¹⁸F-fluciclovine and ⁶⁸Ga-PSMA-11 on separate days. Uptake per patient and in 3 regions per patient - ipsilateral axillary lymph node (LN), extra-axillary LN (ipsilateral supraclavicular or internal mammary), or distant sites of disease - was compared to standard-of-care imaging (CT/bone scan in 13 patients and ¹⁸F-FDG PET-CT in 7 patients). Results were correlated to a composite standard of truth. Confirmed detection rate (cDR) was compared using McNemar's test. Mean SUVmax of ¹⁸F-fluciclovine and ⁶⁸Ga-PSMA-11 in the most avid lesion for each true positive metastatic region and intact primary lesion were compared by t-test.</p><p><strong>Results: </strong>The cDR for standard-of-care imaging was 5/20 patients in 5/60 regions. ⁶⁸Ga-PSMA-11 PET-CT detected metastasis in 7/20 patients in 7/60 regions. ¹⁸F-fluciclovine PET-CT detected metastasis in 9/20 patients in 12/60 regions. The cDR for ¹⁸F-fluciclovine PET-CT was significantly higher versus standard-of-care imaging on the patient and combined region levels, while there were no significant differences between ⁶⁸Ga-PSMA-11 and standard-of care imaging. ¹⁸F-fluciclovine cDR was also significantly higher than ⁶⁸Ga-PSMA-11 on the combined region level. Mean SUVmax for true positive metastatic and primary lesions with ¹⁸F-fluciclovine (n = 18) was significantly greater than for ⁶⁸Ga-PSMA-11 (n = 11) [5.5 ± 1.8 versus 3.5 ± 2.7 respectively, p = 0.021].</p><p><strong>Conclusion: </strong>In this exploratory trial, ¹⁸F-fluciclovine PET-CT has a significantly higher cDR for ILC metastases compared to standard-of-care imaging and to ⁶⁸Ga-PSMA-11. Mean SUVmax for true positive malignancy was significantly higher with ¹⁸F-fluciclovine than for ⁶⁸Ga-PSMA-11. Exploratory data from this trial suggests that molecular imaging of amino acid metabolism in patients with ILC deserves further study.</p><p><strong>Clinical trial registration: </strong>Early phase (I-II) clinical trial (NCT04750473) funded by the National Institutes of Health (R21CA256280).</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":"141554432","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":"[¹⁸F]-D3FSP β-amyloid PET imaging in older adults and alzheimer's disease.","authors":"Anqi Li, Ruiyue Zhao, Mingkai Zhang, Pan Sun, Yue Cai, Lin Zhu, Hank Kung, Ying Han, Xinlu Wang, Tengfei Guo","doi":"10.1007/s00259-024-06835-2","DOIUrl":"10.1007/s00259-024-06835-2","url":null,"abstract":"<p><strong>Purpose: </strong>[¹⁸F]-D3FSP is a new β-amyloid (Aβ) PET imaging tracer designed to decrease nonspecific signals in the brain by reducing the formation of the N-demethylated product. However, its optimal reference region for calculating the standardized uptake value ratio (SUVR) and its relation to the well-established biomarkers of Alzheimer's disease (AD) are still unclear.</p><p><strong>Methods: </strong>We recruited 203 participants from the Greater Bay Area Healthy Aging Brain Study (GHABS) to undergo [¹⁸F]-D3FSP Aβ PET imaging. We analyzed plasma Aβ₄₂/Aβ₄₀, p-Tau₁₈₁, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) using the Simoa platform. We compared the standardized uptake value (SUV) of five reference regions (cerebellum, cerebellum cortex, brainstem/PONs, white matter, composite of the four regions above) and AD typical cortical region (COMPOSITE) SUVR among different clinical groups. The association of D3FSP SUVR with plasma biomarkers, imaging biomarkers, and cognition was also investigated.</p><p><strong>Results: </strong>Brainstem/PONs SUV showed the lowest fluctuation across diagnostic groups, and COMPOSITE D3FSP SUVR had an enormous effect distinguishing cognitively impaired (CI) individuals from cognitively unimpaired (CU) individuals. COMPOSITE SUVR (Referred to brainstem/PONs) was positively correlated with p-Tau₁₈₁ (p < 0.001), GFAP (p < 0.001), NfL (p = 0.014) in plasma and temporal-metaROI tau deposition (p < 0.001), and negatively related to plasma Aβ₄₂/Aβ₄₀ (p < 0.001), temporal-metaROI cortical thickness (p < 0.01), residual hippocampal volume (p < 0.001) and cognition (p < 0.001). The voxel-wise analysis replicated these findings.</p><p><strong>Conclusion: </strong>This study suggests brainstem/PONs as an optimal reference region for calculating D3FSP SUVR to quantify cortical Aβ plaques in the brain. [¹⁸F]-D3FSP could distinguish CI from CU and strongly correlates with well-established plasma biomarkers, tau PET, neurodegeneration, and cognitive decline. However, future head-to-head comparisons of [¹⁸F]-D3FSP PET images with other validated Aβ PET tracers or postmortem results are crucial.</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":"141554431","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":"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":"2024-11-01","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}

{"title":"Diagnostic efficacy of [⁶⁸Ga]Ga-NY104 PET/CT to identify clear cell renal cell carcinoma.","authors":"Wenjia Zhu, Guoyang Zheng, Xinchun Yan, Meixi Liu, Xiaoyuan Li, Yuejuan Cheng, Chunmei Bai, Yushi Zhang, Li Huo","doi":"10.1007/s00259-024-06801-y","DOIUrl":"10.1007/s00259-024-06801-y","url":null,"abstract":"<p><strong>Purpose: </strong>Most clear cell renal cell carcinoma (ccRCC) overexpresses carbonic anhydrase IX (CAIX). [⁶⁸Ga]Ga-NY104 is a small-molecule PET agent selectively targeting CAIX. This study aims to assess the efficacy of [⁶⁸Ga]Ga-NY104 PET/CT to identify ccRCC.</p><p><strong>Materials and methods: </strong>Participants were prospectively recruited in the study (ClinicalTrials.gov: NCT05902377). They were further divided into two groups: group 1, patients with primary renal mass who were scheduled for surgery, group 2, patients with suspected/confirmed metastatic ccRCC. All patients underwent [⁶⁸Ga]Ga-NY104 PET/CT.</p><p><strong>Results: </strong>A total of 47 patients (mean age, 58.8 years ± 13.5, 34 men) were recruited, including 20 patients in group 1 and 27 patients in group 2. The patient-level sensitivity, specificity, and accuracy of [⁶⁸Ga]Ga-NY104 PET scan was 62%, 33%, 58% for group 1 and 95%, 100%, 96% for group 2. [⁶⁸Ga]Ga-NY104 PET identified additional 26 disease regions in 67% (14/21) of patients that were previously unknown. The tumor uptake was correlated with immunohistochemical staining results.</p><p><strong>Conclusions: </strong>^{[68Ga]Ga-NY104} PET/CT has a high diagnostic efficacy for patients with metastatic ccRCC, while it might be of limited value in the diagnosis of primary ccRCC.</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":"141445911","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":"Evaluation of a novel ¹⁷⁷Lu-labelled therapeutic Affibody molecule with a deimmunized ABD domain and improved biodistribution profile.","authors":"Yongsheng Liu, Maryam Oroujeni, Yunqi Liao, Anzhelika Vorobyeva, Vitalina Bodenko, Anna Orlova, Mark Konijnenberg, Matilda Carlqvist, Elisabet Wahlberg, Annika Loftenius, Fredrik Y Frejd, Vladimir Tolmachev","doi":"10.1007/s00259-024-06840-5","DOIUrl":"10.1007/s00259-024-06840-5","url":null,"abstract":"<p><strong>Purpose: </strong>Fusion of Affibody molecules with an albumin-binding domain (ABD) provides targeting agents, which are suitable for radionuclide therapy. To facilitate clinical translation, the low immunogenic potential of such constructs with targeting properties conserved is required.</p><p><strong>Methods: </strong>The HER2-targeting Affibody molecule ZHER2:2891 was fused with a deimmunized ABD variant and DOTA was conjugated to a unique C-terminal cysteine. The novel construct, PEP49989, was labelled with ¹⁷⁷Lu. Affinity, specificity, and in vivo targeting properties of [¹⁷⁷Lu]Lu-PEP49989 were characterised. Experimental therapy in mice with human HER2-expressing xenografts was evaluated.</p><p><strong>Results: </strong>The maximum molar activity of 52 GBq/µmol [¹⁷⁷Lu]Lu-PEP49989 was obtained. [¹⁷⁷Lu]Lu-PEP49989 bound specifically to HER2-expressing cells in vitro and in vivo. The HER2 binding affinity of [¹⁷⁷Lu]Lu-PEP49989 was similar to the affinity of [¹⁷⁷Lu]Lu-ABY-027 containing the parental ABD035 variant. The renal uptake of [¹⁷⁷Lu]Lu-PEP49989 was 1.4-fold higher, but hepatic and splenic uptake was 1.7-2-fold lower than the uptake of [¹⁷⁷Lu]Lu-ABY-027. The median survival of xenograft-bearing mice treated with 21 MBq [¹⁷⁷Lu]Lu-PEP49989 (> 90 days) was significantly longer than the survival of mice treated with vehicle (38 days) or trastuzumab (45 days). Treatment using a combination of [¹⁷⁷Lu]Lu-PEP49989 and trastuzumab increased the number of complete tumour remissions. The renal and hepatic toxicity was minimal to mild.</p><p><strong>Conclusion: </strong>In preclinical studies, [¹⁷⁷Lu]Lu-PEP49989 demonstrated favourable biodistribution and a strong antitumour effect, which was further enhanced by co-treatment with trastuzumab.</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/PMC11527907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616174","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":"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":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527929/pdf/","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":"OA","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":"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":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527917/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatobiliary scintigraphy in post-cholecystectomy patients: added value of morphological dynamic SPECT/CT.","authors":"Gilles Metrard, Aurélien Callaud, Matthieu Bailly","doi":"10.1007/s00259-024-06828-1","DOIUrl":"10.1007/s00259-024-06828-1","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":"141497504","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 role of biomarkers and dosimetry parameters in overall and progression free survival prediction for patients treated with personalized ⁹⁰Y glass microspheres SIRT: a preliminary machine learning study.","authors":"Zahra Mansouri, Yazdan Salimi, Ghasem Hajianfar, Nicola Bianchetto Wolf, Luisa Knappe, Genti Xhepa, Adrien Gleyzolle, Alexis Ricoeur, Valentina Garibotto, Ismini Mainta, Habib Zaidi","doi":"10.1007/s00259-024-06805-8","DOIUrl":"10.1007/s00259-024-06805-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Overall Survival (OS) and Progression-Free Survival (PFS) analyses are crucial metrics for evaluating the efficacy and impact of treatment. This study evaluated the role of clinical biomarkers and dosimetry parameters on survival outcomes of patients undergoing &lt;sup&gt;90&lt;/sup&gt;Y selective internal radiation therapy (SIRT).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials/methods: &lt;/strong&gt;This preliminary and retrospective analysis included 17 patients with hepatocellular carcinoma (HCC) treated with &lt;sup&gt;90&lt;/sup&gt;Y SIRT. The patients underwent personalized treatment planning and voxel-wise dosimetry. After the procedure, the OS and PFS were evaluated. Three structures were delineated including tumoral liver (TL), normal perfused liver (NPL), and whole normal liver (WNL). 289 dose-volume constraints (DVCs) were extracted from dose-volume histograms of physical and biological effective dose (BED) maps calculated on &lt;sup&gt;99m&lt;/sup&gt;Tc-MAA and &lt;sup&gt;90&lt;/sup&gt;Y SPECT/CT images. Subsequently, the DVCs and 16 clinical biomarkers were used as features for univariate and multivariate analysis. Cox proportional hazard ratio (HR) was employed for univariate analysis. HR and the concordance index (C-Index) were calculated for each feature. Using eight different strategies, a cross-combination of various models and feature selection (FS) methods was applied for multivariate analysis. The performance of each model was assessed using an averaged C-Index on a three-fold nested cross-validation framework. The Kaplan-Meier (KM) curve was employed for univariate and machine learning (ML) model performance assessment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The median OS was 11 months [95% CI: 8.5, 13.09], whereas the PFS was seven months [95% CI: 5.6, 10.98]. Univariate analysis demonstrated the presence of Ascites (HR: 9.2[1.8,47]) and the aim of SIRT (segmentectomy, lobectomy, palliative) (HR: 0.066 [0.0057, 0.78]), Aspartate aminotransferase (AST) level (HR:0.1 [0.012-0.86]), and MAA-Dose-V&lt;sub&gt;205&lt;/sub&gt;(%)-TL (HR:8.5[1,72]) as predictors for OS. &lt;sup&gt;90&lt;/sup&gt;Y-derived parameters were associated with PFS but not with OS. MAA-Dose-V&lt;sub&gt;205&lt;/sub&gt;(%)-WNL, MAA-BED-V&lt;sub&gt;400&lt;/sub&gt;(%)-WNL with (HR:13 [1.5-120]) and &lt;sup&gt;90&lt;/sup&gt;Y-Dose-mean-TL, &lt;sup&gt;90&lt;/sup&gt;Y-D&lt;sub&gt;50&lt;/sub&gt;-TL-Gy, &lt;sup&gt;90&lt;/sup&gt;Y-Dose-V&lt;sub&gt;205&lt;/sub&gt;(%)-TL, &lt;sup&gt;90&lt;/sup&gt;Y-Dose- D&lt;sub&gt;50&lt;/sub&gt;-TL-Gy, and &lt;sup&gt;90&lt;/sup&gt;Y-BED-V&lt;sub&gt;400&lt;/sub&gt;(%)-TL (HR:15 [1.8-120]) were highly associated with PFS among dosimetry parameters. The highest C-index observed in multivariate analysis using ML was 0.94 ± 0.13 obtained from Variable Hunting-variable-importance (VH.VIMP) FS and Cox Proportional Hazard model predicting OS, using clinical features. However, the combination of VH. VIMP FS method with a Generalized Linear Model Network model predicting OS using Therapy strategy features outperformed the other models in terms of both C-index and stratification of KM curves (C-Index: 0.93 ± 0.14 and log-rank p-value of 0.023 for ","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":"141563045","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":"⁸⁹Zr-immunoPET-guided selection of a CD33xIL15 fusion protein optimized for antitumor immune cell activation and in vivo tumour retention in acute myeloid leukaemia.","authors":"Natalia Herrero Alvarez, Zaki Molvi, Kyle Lupo, Jessica Urraca, Paul Balderes, Elisabeth K Nyakatura, Abdul G Khan, Tara Viray, Jason S Lewis, Richard J O'Reilly","doi":"10.1007/s00259-024-06814-7","DOIUrl":"10.1007/s00259-024-06814-7","url":null,"abstract":"<p><strong>Purpose: </strong>Immune cells are capable of eliminating leukemic cells, as evidenced by outcomes in hematopoietic cell transplantation (HCT). However, patients who fail induction therapy will not benefit from HCT due to their minimal residual disease (MRD) status. Thus, we aimed to develop an immunomodulatory agent to reduce MRD by activating immune effector cells in the presence of leukaemia cells via a novel fusion protein that chimerises two clinically tolerated biologics: a CD33 antibody and the IL15Ra/IL15 complex (CD33xIL15).</p><p><strong>Methods: </strong>We generated a set of CD33xIL15 fusion protein constructs with varying configurations and identified those with the best in vitro AML-binding, T cell activation, and NK cell potentiation. Using ⁸⁹Zr-immunoPET imaging we then evaluated the biodistribution and in vivo tumour retention of the most favourable CD33xIL15 constructs in an AML xenograft model. Ex vivo biodistribution studies were used to confirm the pharmacokinetics of the constructs.</p><p><strong>Results: </strong>Two of the generated fusion proteins, CD33xIL15 (N72D) and CD33xIL15wt, demonstrated optimal in vitro behaviour and were further evaluated in vivo. These studies revealed that the CD33xIL15wt candidate was capable of being retained in the tumour for as long as its parental CD33 antibody, Lintuzumab (13.9 ± 3.1%ID/g vs 18.6 ± 1.1%ID/g at 120 h).</p><p><strong>Conclusion: </strong>This work demonstrates that CD33xIL15 fusion proteins are capable of targeting leukemic cells and stimulating local T cells in vitro and of concentrating in the tumour in AML xenografts. It also highlights the importance of ⁸⁹Zr-immunoPET to guide the development and selection of tumour-targeted antibody-cytokine fusion proteins.</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":"141579333","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}