Molecular Imaging and Biology最新文献

{"title":"Imaging Cell Surface Plectin in PDAC Patients - A First-In-Human Phase 0 Study Report.","authors":"Julien Dimastromatteo, Jiang He, Reid B Adams, Kimberly A Kelly","doi":"10.1007/s11307-025-02001-8","DOIUrl":"https://doi.org/10.1007/s11307-025-02001-8","url":null,"abstract":"<p><strong>Purpose: </strong>Plectin is traditionally an intracellular cytoskeletal protein that maintains cell structure and stability. However, we and others have identified its surface-localized form in cancer (CSP), where it influences cell adhesion, migration, immune response, and tumor signaling. CSP-positive tumors (pancreatic, lung, ovarian, and breast cancers) contribute to over 3 million annual deaths, highlighting its clinical relevance. This phase 0 study aimed to evaluate PTP-01's ability to target CSP in pancreatic tumors, despite their dense desmoplastic stroma, and to estimate CSP density and tumor vascularity.</p><p><strong>Methods: </strong>Pancreatic cancer patients (n = 3) received an intravenous injection of 100 µg PTP-01 labeled with 370 MBq ¹¹¹In one day before resection. Whole-body planar scintigraphy and SPECT imaging were performed at multiple time points. Resected tumors and adjacent tissues were collected 28 h post-injection. Blood and urine samples were obtained for pharmacokinetic analysis. Tissue biodistribution was assessed using whole-body SPECT scans.</p><p><strong>Results: </strong>PTP-01 injection caused no reported adverse events. Uptake was primarily observed in the kidneys, liver, and bladder, with some tumor uptake. CSP density in tumors was estimated at 10⁶ molecules per cell. The elimination half-life (T₁/₂) ranged from 5 to 22 h across patients.</p><p><strong>Conclusion: </strong>PTP-01 imaging of pancreatic tumors revealed the ability of a targeted agent to bind to CSP. Further, CSP density in tumors was estimated to be on par with other surface molecules such as Her2 with effective targeted therapies. This study suggests that CSP is a highly expressed, accessible molecule for the development of targeted therapies such as antibodies or antibody-drug conjugates.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Neoadjuvant Therapies Do Not Reduce Epidermal Growth Factor Receptor (EGFR) Expression or EGFR-Targeted Fluorescence in a Murine Model of Soft-Tissue Sarcomas.","authors":"Samuel S Streeter, Xiaochun Xu, Kendra A Hebert, Paul M Werth, P Jack Hoopes, Lesley A Jarvis, Brian W Pogue, Keith D Paulsen, Kimberley S Samkoe, Eric R Henderson","doi":"10.1007/s11307-025-01999-1","DOIUrl":"https://doi.org/10.1007/s11307-025-01999-1","url":null,"abstract":"","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ex-vivo Imaging of Glial Energy Metabolism in the Neonatal Mouse Brain during Convulsive Seizures with Intranasal Radiotracer Administration.","authors":"Rie Hosoi, Kenya Tada, Takahiro Hayakawa, Yuka Haga","doi":"10.1007/s11307-025-02000-9","DOIUrl":"https://doi.org/10.1007/s11307-025-02000-9","url":null,"abstract":"<p><strong>Purpose: </strong>In this study, we examined changes in glial energy metabolism in neonatal mouse brain images obtained under pathological conditions following intranasal administration of the radiotracer [2-¹⁴C]acetate.</p><p><strong>Procedures: </strong>[2-¹⁴C]acetate was administered via the mouse nasal cavity, after which autoradiograms of the brain of 7-day-old mice were obtained. Radio thin-layer chromatography was applied for metabolite analysis of brain radioactivity. We also compared brain uptake of [2-¹⁴C]acetate when administrated intranasally and intravenously in 3-week-old mice. To confirm selective uptake by glial cells, [2-¹⁴C]acetate was injected into the nasal cavity of mice injected with a glial toxin in the brain. Pentylenetetrazole (PTZ) was applied to induce seizures.</p><p><strong>Results: </strong>Intranasally administered [2-¹⁴C]acetate was rapidly incorporated into the brains of 7-day-old mice, reaching its highest uptake level 20 min after administration. After 20 min of intranasal [2-¹⁴C]acetate administration, glutamate and glutamine accounted for 32 ± 2.5% and 30 ± 3.4% of total brain radioactivity, respectively. There was no difference in the radioactivity distribution in the brain between intranasal and intravenous administration, except in the ventral olfactory bulb in 3-week-old mice. Microinjection of the glial-specific toxin fluorocitrate reduced the accumulation of radioactivity in the brain by 60% following intranasal administration in 3-week-old mice. The uptake of [2-¹⁴C]acetate in the brains of 7-day-old mice significantly decreased 30 min after systemic PTZ administration, suggesting a decrease in energy metabolism in glial cells during seizures.</p><p><strong>Conclusions: </strong>Quantitative images of biological functions in the neonatal mouse brain can be obtained by intranasal administration. This technique allowed the observation of a decrease in acetate uptake associated with convulsive seizures. The results of this study could be applied to the imaging of biological brain functions and research on neurological disorders using labeled probes in neonatal mice.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a CT-less SPECT Acquisition Protocol for Kidney Dosimetry in ¹⁷⁷Lu-PSMA-617 Radioligand Therapy.","authors":"Christian Happel, Larissa Völler, Benjamin Bockisch, Daniel Groener, Britta Leonhäuser, Frank Grünwald, Amir Sabet","doi":"10.1007/s11307-025-01998-2","DOIUrl":"https://doi.org/10.1007/s11307-025-01998-2","url":null,"abstract":"<p><strong>Purpose: </strong>Targeted radioligand therapy of metastatic castration-resistant prostate cancer (mCRPC) with ¹⁷⁷Lu-PSMA (RLT) requires sufficient dose monitoring of the kidneys. Currently, dosimetry using SPECT/CT-imaging is the most preferred method. However, SPECT/CT is a time-consuming procedure and comprises additional radiation exposure to the patient. Moreover, not every therapeutic nuclear medicine facility has access to SPECT/CT. Therefore, the aim of this study was to develop a new procedure of kidney dosimetry without the use of SPECT/CT and evaluate this method in a large cohort of patients with mCRPC undergoing RLT.</p><p><strong>Procedures: </strong>A dedicated torso phantom with kidneys filled with a solution of ¹⁷⁷Lu-PSMA was used for quantitative calibration of a SPECT-camera. The calculated sensitivity was adapted according to the individual attenuation of the patient in four directions from the kidney surface to the body surface (ventral, dorsal, left and right) obtained from a previously performed CT. A total of 196 patients undergoing 926 cycles of ¹⁷⁷Lu-PSMA therapy were retrospectively analyzed. Abdominal SPECT was performed 24, 48 and 72 h after administration of ¹⁷⁷Lu-PSMA including scatter and dead-time correction in every patient. Kidney dose was calculated using an individual attenuation-based procedure and compared to values from international literature.</p><p><strong>Results: </strong>Volumes of interest of the kidneys were drawn in the three sequential SPECT-images to calculate intra-renal effective half-life. Absolute quantification of activity in the kidneys was accomplished obtaining a patient individual sensitivity based on the individual attenuation in the patient. Kidney dose was then calculated applying a bi-exponential time activity curve in Microsoft EXCEL. Mean kidney dose per administered activity was 0.54 (± 0.26) Gy/GBq.</p><p><strong>Conclusions: </strong>With the presented procedure a reliable kidney dosimetry is possible without the use of SPECT/CT. Facilities without SPECT/CT are therefore able to perform an adequate kidney dosimetry without additional radiation exposure for the patient.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Background Tissue with Native Target Expression Can Determine Presence of Nodal Metastasis in Head and Neck Squamous Cell Carcinoma Patients Infused with Targeted Fluorescent Tracers.","authors":"Nicole Meeks, Sherin James, Giri Krishnan, Akhilesh Wodeyar, Hidenori Tanaka, Benjamin B Kasten, Yu-Jin Lee, Marisa E Hom, Eben L Rosenthal, Jason M Warram","doi":"10.1007/s11307-025-01996-4","DOIUrl":"https://doi.org/10.1007/s11307-025-01996-4","url":null,"abstract":"<p><strong>Purpose: </strong>Survival and treatment intensity in patients with head and neck squamous cell carcinoma (HNSCC) is determined by the presence of lymph node (LN) metastasis, and as a result surgical removal of potentially affected LN remains a mainstay practice. Fluorescence guided surgery (FGS) using targeted optical agents is an expanding field that shows great potential for aiding diagnosis of metastatic LN. Given variations in fluorescence background, a reference standard for regions of interest is necessary for cross patient comparison. The present study aims to determine whether tissue with native target expression can be used as a background to determine metastatic LN in patients with HNSCC infused with anti-epidermal growth factor receptor (EGFR) targeted imaging agents.</p><p><strong>Procedures: </strong>Twenty-two patients infused with panitumumab-IRDye800 or cetuximab-IRDye800 prior to surgery were included. Fluorescence imaging and analysis was performed on resected LNs (N = 843) using the submandibular glands (SMG) and skin as reference standard tissue with known EGFR antigen expression.</p><p><strong>Results: </strong>Sixteen patients (72.7%) had at least one positive LN on final pathology. The LN to SMG (LN/SMG) and LN to skin (LN/skin) ratios were significantly higher in metastatic LN compared to benign LN (p < 0.0001 for both). Using patient-specific ratios to determine an optimal LN/skin cutoff was the most sensitive (95.2%) and directly comparing the LN/skin ratio of all patients to determine a cutoff was the most specific (86.3%).</p><p><strong>Conclusions: </strong>In HNSCC patients infused with a molecularly targeted fluorescent tracer, endogenous expression of the target antigen can be used as a reference standard to detect LN metastasis. Additionally, the performance of the background in determining metastatic LN can be improved by utilizing patient-specific reference standards.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Anti-CEA C_H2 Domain-Deleted Antibody (M5A∆C_H2) for the PET Imaging of Colorectal Cancer.","authors":"Jitender Jitender, Teresa Hong, Anakim Sherman, Patty Wong, Eric Aniogo, Maciej Kujawski, John E Shively, Paul J Yazaki","doi":"10.1007/s11307-025-01997-3","DOIUrl":"https://doi.org/10.1007/s11307-025-01997-3","url":null,"abstract":"<p><strong>Purpose: </strong>Recombinant antibody fragments represent a novel class of in vivo biological immunoPET imaging agents. This study developed a series of anti-carcinoembryonic antigen (CEA) C_H2 domain-deleted antibodies to evaluate their rapid, high-level tumor targeting combined with fast blood clearance for immunoPET imaging in two colorectal cancer mouse models.</p><p><strong>Procedure: </strong>A series of humanized anti-CEA M5A∆C_H2 recombinant antibody fragments were synthesized via transient mammalian expression and purified using a two-step process. The M5A∆CH2 antibody series was characterized by HPLC-SEC, SDS-PAGE and binding affinities. The M5A∆C_H2-C5 antibody, which has five disulfide bridges in the modified IgG1/IgG3 hinge domain, was selected for positron emission tomography (PET) imaging. Site-specific thiol conjugation of the reduced hinge disulfides with the 1,4,7,10 tetraazacyclododecane-1,4,7-triacetic acid trisodium salt-vinyl sulfone (DO3A-VS) chelate was performed, followed by labeling with [⁶⁴Cu-CuCl₂]. The [⁶⁴Cu]Cu-DO3A-M5A∆C_H2-C5 was evaluated for CEA-positive tumor PET imaging at serial time points, pharmacokinetics and a terminal biodistribution study conducted in two CEA-positive colorectal cancer mouse models.</p><p><strong>Results: </strong>The anti-CEA M5A∆C_H2 antibodies had high expression, were purified using a new CH3 domain affinity resin and were stable up to one year. ImmunoPET imaging and biodistribution studies were performed in athymic mice bearing human colorectal cancer LS174T tumors and immunocompetent transgenic-CEA (Tg-CEA) mice bearing MC-38 tumors transfected with the human CEA gene. The [⁶⁴Cu]Cu-DO3A-M5A∆C_H2-C5 showed rapid, high tumor localization and the expected fast blood clearance.</p><p><strong>Conclusions: </strong>A series of humanized anti-CEA M5A∆C_H2 antibodies were designed for immunoPET imaging of colorectal cancer, and the [⁶⁴Cu]Cu-DO3A-M5A∆C_H2-C5 showed high tumor targeting and fast blood clearance supporting its potential for clinical trials.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of Radiomics, Dosiomics, and Dose Volume Histograms for Tumor Response Prediction in Hepatocellular Carcinoma following ⁹⁰Y-SIRT.","authors":"Zahra Mansouri, Yazdan Salimi, Ghasem Hajianfar, Luisa Knappe, Nicola Bianchetto Wolf, Genti Xhepa, Adrien Gleyzolle, Alexis Ricoeur, Valentina Garibotto, Ismini Mainta, Habib Zaidi","doi":"10.1007/s11307-025-01992-8","DOIUrl":"https://doi.org/10.1007/s11307-025-01992-8","url":null,"abstract":"<p><strong>Purpose: </strong>We evaluate the role of radiomics, dosiomics, and dose-volume constraints (DVCs) in predicting the response of hepatocellular carcinoma to selective internal radiation therapy with ⁹⁰Y with glass microspheres.</p><p><strong>Methods: </strong>^99mTc-macroagregated albumin (^99mTc-MAA) and ⁹⁰Y SPECT/CT images of 17 patients were included. Tumor responses at three months were evaluated using modified response evaluation criteria in solid tumors criteria and patients were categorized as responders or non-responders. Dosimetry was conducted using the local deposition method (Dose) and biologically effective dosimetry. A total of 264 DVCs, 321 radiomic features, and 321 dosiomic features were extracted from the tumor, normal perfused liver (NPL), and whole normal liver (WNL). Five different feature selection methods in combination with eight machine learning algorithms were employed. Model performance was evaluated using area under the AUC, accuracy, sensitivity, and specificity.</p><p><strong>Results: </strong>No statistically significant differences were observed between neither the dose metrics nor radiomicas or dosiomics features of responders and non-responder groups. ⁹⁰Y-dosiomics models with any given set of inputs outperformed other models. This was also true for ⁹⁰Y-radiomics from SPECT and SPECT-clinical features, achieving an AUC, accuracy, sensitivity, and specificity of 1. Among MAA-dosiomic and radiomic models, two models showed AUC ≥ 0.91. While the performance of MAA-dose volume histogram (DVH)-based models were less promising, the ⁹⁰Y-DVH-based models showed strong performance (AUC ≥ 0.91) when considered independently of clinical features.</p><p><strong>Conclusion: </strong>This study demonstrated the potential of ^99mTc-MAA and ⁹⁰Y SPECT-derived radiomics, dosiomics, and dosimetry metrics in establishing predictive models for tumor response.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Targeting of Neuropilin-1 and Glucose Transporter for Efficient Fluorescence Imaging of Cancer.","authors":"Jianwei Zhu, Can Zhou, Jian Yang, Zhenhua Wang","doi":"10.1007/s11307-025-01993-7","DOIUrl":"https://doi.org/10.1007/s11307-025-01993-7","url":null,"abstract":"<p><strong>Purpose: </strong>Early diagnosis and complete resection of cancer are pivotal for enhancing patient survival rates and prognosis. However, a significant current challenge lies in the lack of specific imaging probes for the identifying various tumor types. The expression levels of neuropilin-1 (NRP1) and glucose transporter 1 (GLUT1) in most tumors, including breast cancer, are closely linked to tumor proliferation and metastasis. This study seeks to develop a novel near-infrared fluorescence (NIRF) probe aimed at precise tumor detection by targeting NRP1 and GLUT1.</p><p><strong>Procedures: </strong>G₀ was conjugated with N₃-PEG₄-ALKADK and 2-Azido-2-deoxy-D-glucose to synthesize the NGF probe. The spectral properties (fluorescence and absorbance spectra) of NGF were studied in both methanol and water. The targeting specificity of NGF towards NRP1 and GLUT1 was evaluated using confocal fluorescence microscopy imaging, flow cytometry assays and in vivo IVIS spectrum imaging.</p><p><strong>Results: </strong>A dual-targeting fluorescent probe named NGF was successfully synthesized to bind to both NRP1 and GLUT1 receptors. NGF exhibited greater hydrophilicity (Log P = -0.95 ± 0.07) and superior optical properties compared to its precursor, G₀. Confocal fluorescence imaging, flow cytometry assays, and blocking studies revealed that the cellular uptake of NGF correlated with the NRP1 and GLUT1 expression levels across cell lines. Moreover, a strong linear relationship (R² = 0.98) was observed between fluorescence intensity and increasing NGF concentrations in MDA-MB-231 cells. In vivo IVIS imaging in animal models demonstrated specific binding of NGF to breast cancer (MDA-MB-231) and colorectal cancer (HCT116), with prolonged retention observed up to 72 h.</p><p><strong>Conclusions: </strong>This study highlighted the efficient targeting and sustained retention of the dual-target heterodimeric fluorescent probe NGF, binding to NRP1 and GLUT1 receptors. These findings suggest significant potential for clinical applications in early cancer detection and fluorescence image-guided surgery.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Preclinical Development of Near-Infrared-Labeled CD38-Targeted Daratumumab for Optical Imaging of CD38 in Multiple Myeloma.","authors":"Nicholas Cho, Sooah Ko, Monica Shokeen","doi":"10.1007/s11307-025-01984-8","DOIUrl":"https://doi.org/10.1007/s11307-025-01984-8","url":null,"abstract":"","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Evaluation of [¹⁸F]AlF NOTA-5G, an Aluminum [¹⁸F]fluoride Labeled Peptide Targeting the Cell Surface Receptor Integrin Alpha(v)beta(6) for PET Imaging.","authors":"Sven H Hausner, Ryan A Davis, Tanushree Ganguly, Rebecca Harris, Julie L Sutcliffe","doi":"10.1007/s11307-025-01995-5","DOIUrl":"https://doi.org/10.1007/s11307-025-01995-5","url":null,"abstract":"","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}