Molecular Imaging最新文献

{"title":"Radiochemistry and Preclinical PET Imaging of ⁶⁸Ga-Desferrioxamine Radiotracers Targeting Prostate-Specific Membrane Antigen.","authors":"Eleni Gourni,&nbsp;Luigi Del Pozzo,&nbsp;Mark Bartholomä,&nbsp;Yvonne Kiefer,&nbsp;Philipp T Meyer,&nbsp;Helmut R Maecke,&nbsp;Jason P Holland","doi":"10.1177/1536012117737010","DOIUrl":"https://doi.org/10.1177/1536012117737010","url":null,"abstract":"<p><p>Radiotracers incorporating the urea-based Glu-NH-C(O)-NH-Lys group have gained prominence due to their role in targeting prostate-specific membrane antigen (PSMA)-a clinical biomarker of prostate cancer. Here, the synthesis, radiolabeling, and in vitro and in vivo characterization of two ⁶⁸Ga-radiolabeled Glu-NH-C(O)-NH-Lys radiotracers conjugated to the desferrioxamine B (DFO) chelate were evaluated. Two linker groups based on amide bond and thiourea coupling chemistries were employed to develop ⁶⁸Ga-DFO-Nsucc-PSMA (⁶⁸Ga-4) and ⁶⁸Ga-DFO- pNCS-Bn-PSMA (⁶⁸Ga-7), respectively. Radiosynthesis proceeded quantitatively at room temperature with high radiochemical yields, chemical/radiochemical purities, and specific activities. Pharmacokinetic profiles of ⁶⁸Ga-4 and ⁶⁸Ga-7 were assessed using positron-emission tomography (PET) in mice bearing subcutaneous LNCaP tumors. Data were compared to the current clinical benchmark radiotracer ⁶⁸Ga-HBED-CC-PSMA (⁶⁸Ga-1) (HBED = N,N'-Bis(2-hydroxy-5-(ethylene-beta-carboxy)benzyl)ethylenediamine N,N'-diacetic acid). Results indicated that the target binding affinity, protein association, blood pool and background organ clearance properties, and uptake in PSMA-positive lesions are strongly dependent on the nature of the chelate, the linker, and the spacer groups. Protein dissociation constants ( K_d values) were found to be predictive of pharmacokinetics in vivo. Compared to ⁶⁸Ga-1, ⁶⁸Ga-4 and ⁶⁸Ga-7 resulted in decreased tumor uptake but enhanced blood pool clearance and reduced residence time in the kidney. The study highlights the importance of maximizing protein binding affinity during radiotracer optimization.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117737010"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012117737010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35571396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging of Myocardial Ischemia-Reperfusion Injury Using Sodium [¹⁸F]Fluoride Positron Emission Tomography/Computed Tomography in Rats and Humans.","authors":"Hongyoon Choi,&nbsp;Jeong Hee Han,&nbsp;Sue Yeon Lim,&nbsp;Inki Lee,&nbsp;Young-Seok Cho,&nbsp;Eun Ju Chun,&nbsp;Won Woo Lee","doi":"10.1177/1536012117704767","DOIUrl":"https://doi.org/10.1177/1536012117704767","url":null,"abstract":"<p><p>Positron emission tomography (PET)/computed tomography (CT) using sodium [¹⁸F]fluoride (Na[¹⁸F]F) has been proven to be a promising hot-spot imaging modality for myocardial infarction (MI). We investigated Na[¹⁸F]F uptake in ischemia-reperfusion injury (IRI) of rats and humans. Sodium [¹⁸F]fluoride PET/CT was performed in Sprague-Dawley rats that had IRI surgery, and it readily demonstrated prominent Na[¹⁸F]F uptake in the infarct area post-IRI. Sodium [¹⁸F]fluoride uptake was matched with negative 2,3,5-triphenyl-2 H-tetrazolium chloride staining results, accompanied by myocardial apoptosis and associated with positive calcium staining results. Furthermore, area at risk was negative for Na[¹⁸F]F uptake. Cyclosporine A (CysA) treatment reduced standardized uptake value of ¹⁸F over the infarct area, and a significant decrease in infarct size was also observed by the CysA treatment. In humans, Na[¹⁸F]F PET/CT readily demonstrated increased Na[¹⁸F]F uptake in the 2 patients with MI post-percutaneous coronary intervention. In conclusion, this study sheds light on the potential utility of Na[¹⁸F]F PET/CT as a hot-spot imaging modality for myocardial IRI.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117704767"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012117704767","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35122871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluorescent, Plasmonic, and Radiotherapeutic Properties of the ¹⁷⁷Lu-Dendrimer-AuNP-Folate-Bombesin Nanoprobe Located Inside Cancer Cells.","authors":"Héctor Mendoza-Nava,&nbsp;Guillermina Ferro-Flores,&nbsp;Flor de María Ramírez,&nbsp;Blanca Ocampo-García,&nbsp;Clara Santos-Cuevas,&nbsp;Erika Azorín-Vega,&nbsp;Nallely Jiménez-Mancilla,&nbsp;Myrna Luna-Gutiérrez,&nbsp;Keila Isaac-Olivé","doi":"10.1177/1536012117704768","DOIUrl":"https://doi.org/10.1177/1536012117704768","url":null,"abstract":"<p><p>The integration of fluorescence and plasmonic properties into one molecule is of importance in developing multifunctional imaging and therapy nanoprobes. The aim of this research was to evaluate the fluorescent properties and the plasmonic-photothermal, therapeutic, and radiotherapeutic potential of ¹⁷⁷Lu-dendrimer conjugated to folate and bombesin with gold nanoparticles in the dendritic cavity (¹⁷⁷Lu-DenAuNP-folate-bombesin) when it is internalized in T47D breast cancer cells. The intense near-Infrared (NIR) fluorescence emitted at 825 nm from the conjugate inside cells corroborated the usefulness of DenAuNP-folate-bombesin for optical imaging. After laser irradiation, the presence of the nanosystem in cells caused a significant increase in the temperature of the medium (46.8°C, compared to 39.1°C without DenAuNP-folate-bombesin, P < 0.05), resulting in a significant decrease in cell viability (down to 16.51% ± 1.52%) due to the ¹⁷⁷Lu-DenAuNP-folate-bombesin plasmonic properties. After treatment with ¹⁷⁷Lu-DenAuNP-folate-bombesin, the T47D cell viability decreased 90% because of the radiation-absorbed dose (63.16 ± 4.20 Gy) delivered inside the cells. The ¹⁷⁷Lu-DenAuNP-folate-bombesin nanoprobe internalized in cancer cells exhibited properties suitable for optical imaging, plasmonic-photothermal therapy, and targeted radiotherapy.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117704768"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012117704768","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35122873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-Energy SPECT and the Development of Peptide p5+14 for Imaging Amyloidosis.","authors":"Jonathan S Wall, Stephen J Kennel, Emily B Martin","doi":"10.1177/1536012117708705","DOIUrl":"10.1177/1536012117708705","url":null,"abstract":"<p><p>Amyloidosis is associated with a number of rare diseases and is characterized by the deposition, in abdominothoracic organs and peripheral nerves, of extracellular protein fibrils, which leads to dysfunction and severe morbidity. Effective clinical evaluation and management of patients with systemic amyloidosis are hampered by the lack of a noninvasive, quantitative method for detecting whole-body amyloid load. We have used a battery of assays including dual-energy SPECT imaging and comparative effectiveness studies in support of translation of a synthetic polybasic peptide, p5+14, as a novel radiotracer for visualization of amyloidosis by molecular imaging. These data provide support for a phase 1 positron emission tomography/computed tomography imaging trial of this reagent, labeled with iodine-124, in patients with all forms of systemic amyloidosis.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117708705"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/c4/10.1177_1536012117708705.PMC5469514.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35122875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking Brain Cancer Therapy: Tumor Enzyme Activatable Theranostic Nanoparticles.","authors":"Heike E Daldrup-Link","doi":"10.1177/1536012117730950","DOIUrl":"10.1177/1536012117730950","url":null,"abstract":"<p><p>This invited commentary discusses a recent article by Mohanty et al in Molecular Cancer Therapeutics about significant therapeutic efficacies of novel theranostic nanoparticles (TNPs) for the treatment of human brain cancers in mouse models. The TNPs were cleaved by enzymes in the tumor tissue, matrix metalloproteinase (MMP-14), which lead to release of a highly potent therapeutic drug, azademethylcolchicine. Data showed that the TNPs caused selective toxic effects in MMP-14-expressing glioblastoma and not normal brain. In addition, the iron oxide nanoparticle backbone enabled in vivo drug tracking with magnetic resonance imaging (MRI). This commentary discusses previous efforts of MMP-targeted therapeutics as well as opportunities for further refinements of tumor enzyme-activatable TNPs. If successfully translated to clinical applications, the TNPs might hold substantial potential to improving cytotoxic indexes and long-term outcomes of patients with brain cancer compared to standard therapy.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117730950"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2c/0c/10.1177_1536012117730950.PMC5613837.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35426836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging Bone-Cartilage Interactions in Osteoarthritis Using [¹⁸F]-NaF PET-MRI.","authors":"Dragana Savic,&nbsp;Valentina Pedoia,&nbsp;Youngho Seo,&nbsp;Jaewon Yang,&nbsp;Matt Bucknor,&nbsp;Benjamin L Franc,&nbsp;Sharmila Majumdar","doi":"10.1177/1536012116683597","DOIUrl":"https://doi.org/10.1177/1536012116683597","url":null,"abstract":"<p><strong>Purpose: </strong>Simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI) is an emerging technology providing both anatomical and functional images without increasing the scan time. Compared to the traditional PET/computed tomography imaging, it also exposes the patient to significantly less radiation and provides better anatomical images as MRI provides superior soft tissue characterization. Using PET-MRI, we aim to study interactions between cartilage composition and bone function simultaneously, in knee osteoarthritis (OA).</p><p><strong>Procedures: </strong>In this article, bone turnover and remodeling was studied using [¹⁸F]-sodium fluoride (NaF) PET data. Quantitative MR-derived T_1ρ relaxation times characterized the biochemical cartilage degeneration. Sixteen participants with early signs of OA of the knee received intravenous injections of [¹⁸F]-NaF at the onset of PET-MR image acquisition. Regions of interest were identified, and kinetic analysis of dynamic PET data provided the rate of uptake ( K_i) and the normalized uptake (standardized uptake value) of [¹⁸F]-NaF in the bone. Morphological MR images and quantitative voxel-based T_1ρ maps of cartilage were obtained using an atlas-based registration technique to segment cartilage automatically. Voxel-by-voxel statistical parameter mapping was used to investigate the relationship between bone and cartilage.</p><p><strong>Results: </strong>Increases in cartilage T_1ρ, indicating degenerative changes, were associated with increased turnover in the adjoining bone but reduced turnover in the nonadjoining compartments. Associations between pain and increased bone uptake were seen in the absence of morphological lesions in cartilage, but the relationship was reversed in the presence of incident cartilage lesions.</p><p><strong>Conclusion: </strong>This study shows significant cartilage and bone interactions in OA of the knee joint using simultaneous [¹⁸F]-NaF PET-MR, the first in human study. These observations highlight the complex biomechanical and biochemical interactions in the whole knee joint in OA, which potentially could help assess therapeutic targets in treating OA.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"15 ","pages":"1-12"},"PeriodicalIF":2.8,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012116683597","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35122789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Imaging of the Human Pulmonary Vascular Endothelium Using an Adrenomedullin Receptor Ligand.","authors":"François Harel,&nbsp;Xavier Levac,&nbsp;Quang T Nguyen,&nbsp;Myriam Létourneau,&nbsp;Sophie Marcil,&nbsp;Vincent Finnerty,&nbsp;Mariève Cossette,&nbsp;Alain Fournier,&nbsp;Jocelyn Dupuis","doi":"10.2310/7290.2015.00003","DOIUrl":"https://doi.org/10.2310/7290.2015.00003","url":null,"abstract":"<p><p>This phase I study (NCT01539889) evaluated the safety, efficacy, and dosing of PulmoBind for molecular imaging of pulmonary circulation. PulmoBind is a ligand of the adrenomedullin receptor abundantly distributed in lung capillaries. Labeled with ^99mTc, it allows single-photon emission computed tomographic (SPECT) imaging of lung perfusion. In preclinical studies, PulmoBind scans enabled detection of lung perfusion defects and quantification of microcirculatory occlusion caused by pulmonary hypertension. Healthy humans ( N = 20) were included into escalating groups of 5 mCi ( n = 5), 10 mCi ( n = 5), or 15 mCi ( n = 10) ^99mTc-PulmoBind. SPECT imaging was serially performed, and ^99mTc-PulmoBind dosimetric analysis was accomplished. The radiochemical purity of ^99mTc-PulmoBind was greater than 95%. There were no safety concerns at the three dosages studied. Imaging revealed predominant and prolonged lung uptake with a mean peak extraction of 58% ± 7%. PulmoBind was well tolerated, with no clinically significant adverse event related to the study drug. The highest dose of 15 mCi provided a favorable dosimetric profile and excellent imaging. The postural lung perfusion gradient was detectable. ^99mTc-PulmoBind is safe and provides good quality lung perfusion imaging. The safety/efficacy of this agent can be tested in disorders of pulmonary circulation such as pulmonary arterial hypertension.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"14 5","pages":"7290201500003"},"PeriodicalIF":2.8,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2310/7290.2015.00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35121575","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":"Monitoring Tumor Targeting and Treatment Effects of IRDye 800CW and GX1-Conjugated Polylactic Acid Nanoparticles Encapsulating Endostar on Glioma by Optical Molecular Imaging.","authors":"Yaqian Li,&nbsp;Yang Du,&nbsp;Xia Liu,&nbsp;Qian Zhang,&nbsp;Lijia Jing,&nbsp;Xiaolong Liang,&nbsp;Chongwei Chi,&nbsp;Zhifei Dai,&nbsp;Jie Tian","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Molecular imaging used in cancer diagnosis and therapeutic response monitoring is important for glioblastoma (GBM) research. Antiangiogenic therapy currently is one of the emerging approaches for GBM treatment. In this study, a multifunctional nanoparticle was fabricated that can facilitate the fluorescence imaging of tumor and deliver a therapeutic agent to the tumor region in vivo and therefore possesses broad application in cancer diagnosis and treatment. This particle was polylactic acid (PLA) nanoparticles encapsulating Endostar, which was further conjugated with GX1 peptide and the near-infrared (NIR) dye IRDye 800CW (IGPNE). We demonstrated noninvasive angiogenesis targeting and therapy of IGPNE on U87MG xenografts in vivo using dual-modality optical molecular imaging including NIR fluorescence molecular imaging (FMI) and bioluminescence imaging (BLI). The NIR FMI results demonstrated that IGPNE had more accumulation to the tumor site compared to free IRDye 800CW. To further evaluate the antitumor treatment efficacy of IGPNE, BLI and immunohistochemistry analysis were performed on tumor-bearing mice. With the aid of molecular imaging, the results confirmed that IGPNE enhanced antitumor treatment efficacy compared to free Endostar. In conclusion, IGPNE realizes real-time imaging of U87MG tumors and improves the antiangiogenic therapeutic efficacy in vivo.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"14 ","pages":"356-65"},"PeriodicalIF":2.8,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34278838","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":"PET Imaging of Steroid Hormone Receptor Expression.","authors":"Louis Allott, Graham Smith, Eric O Aboagye, Laurence Carroll","doi":"10.2310/7290.2015.00026","DOIUrl":"10.2310/7290.2015.00026","url":null,"abstract":"<p><p>Steroid hormone receptor (SHR) expression and changes in SHR expression compared to basal levels, whether upregulated, downregulated, or mutated, form a distinguishing feature of some breast, ovarian, and prostate cancers. These receptors act to induce tumor proliferation. In the imaging context, total expression together with modulation of expression can yield predictive and prognostic information. Currently, biopsy for histologic assessment of SHR expression is routine for breast and prostate cancer; however, the technique is not well suited to the heterogeneous tumor environment and can lead to incorrect receptor expression assignment, which precludes effective treatment. The development of positron emission tomography (PET) radioligands to image receptor expression may overcome the difficulties associated with tumor heterogeneity and facilitate the assessment of metastatic disease.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"14 10","pages":"534-50"},"PeriodicalIF":2.8,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34188291","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":"[11C]Carfentanil Binds Preferentially to μ-Opioid Receptor Subtype 1 Compared to Subtype 2.","authors":"Olof Eriksson,&nbsp;Gunnar Antoni","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The positron emission tomography (PET) ligand [(11)C]carfentanil is a selective agonist for μ-opioid receptors and has been used for studying μ-opioid receptors in the human brain. However, it is unknown if [(11)C]carfentanil binding differentiates between subtype receptors μ1 and μ2. In this study, we investigated whether μ1 and μ2 can be studied separately through receptor subtype-selective inhibition of [(11)C]carfentanil by pharmacologic intervention. [(11)C]Carfentanil binding characteristics on rat brain sections were assessed either alone or in the presence of the μ-receptor inhibitor cyprodime or the μ1-specific inhibitor naloxonazine. [(11)C]Carfentanil binding in the living rat brain was similarly studied by small animal PET/computed tomography during baseline conditions or following displacement by cyprodime or naloxonazine. Autoradiography binding studies on rat brain sections demonstrated that [(11)C]carfentanil has higher affinity and binding potential for μ1 than for μ2. [(11)C]Carfentanil binding to μ2 in vivo could not be detected following specific blocking of μ1, as predicted from the low binding potential for μ2 as measured in vitro. [(11)C]Carfentanil binding is preferential for μ1 compared to μ2 in vitro and in vivo. Clinical studies employing [(11)C]carfentanil are therefore likely biased to measure μ1 rather than μ2.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"14 ","pages":"476-83"},"PeriodicalIF":2.8,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34251820","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}