Journal of labelled compounds & radiopharmaceuticals最新文献

{"title":"Development and physicochemical characterization of a biodegradable microspheres formulation loaded with samarium-153 and doxorubicin for chemo-radioembolization of liver tumours","authors":"Asseel Hisham Alregib,&nbsp;Hun Yee Tan,&nbsp;Yin How Wong,&nbsp;Azahari Kasbollah,&nbsp;Eng Hwa Wong,&nbsp;Basri Johan Jeet Abdullah,&nbsp;Alan Christopher Perkins,&nbsp;Chai Hong Yeong","doi":"10.1002/jlcr.4046","DOIUrl":"10.1002/jlcr.4046","url":null,"abstract":"<p>Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are promising treatments for unresectable liver tumours. Some recent studies suggested that combining TACE and TARE in one treatment course might improve treatment efficacy through synergistic cytotoxicity effects. Nonetheless, current formulations do not facilitate a combination of chemo- and radio-embolic agents in one delivery system. Therefore, this study aimed to synthesise a hybrid biodegradable microsphere loaded with both radioactive agent, samarium-153 (¹⁵³Sm) and chemotherapeutic drug, doxorubicin (Dox) for potential radio-chemoembolization of advanced liver tumours. ¹⁵²Sm and Dox-loaded polyhydroxybutyrate-co-3-hydroxyvalerate (PHBV) microspheres were prepared using water-in-oil-in-water solvent evaporation method. The microspheres were then sent for neutron activation in a neutron flux of 2 × 10¹² n/cm²/s. The physicochemical properties, radioactivity, radionuclide purity, ¹⁵³Sm retention efficiency, and Dox release profile of the Dox-¹⁵³Sm-PHBV microspheres were analysed. In addition, in vitro cytotoxicity of the formulation was tested using MTT assay on HepG2 cell line at 24 and 72 h. The mean diameter of the Dox-¹⁵³Sm-PHBV microspheres was 30.08 ± 2.79 μm. The specific radioactivity was 8.68 ± 0.17 GBq/g, or 177.69 Bq per microsphere. The ¹⁵³Sm retention efficiency was more than 99%, tested in phosphate-buffered saline (PBS) and human blood plasma over 26 days. The cumulative release of Dox from the microspheres after 41 days was 65.21 ± 1.96% and 29.96 ± 0.03% in PBS solution of pH 7.4 and pH 5.5, respectively. The Dox-¹⁵³Sm-PHBV microspheres achieved a greater in vitro cytotoxicity effect on HepG2 cells (85.73 ± 3.63%) than ¹⁵³Sm-PHBV (70.03 ± 5.61%) and Dox-PHBV (74.06 ± 0.78%) microspheres at 300 μg/mL at 72 h. In conclusion, a novel biodegradable microspheres formulation loaded with chemotherapeutic drug (Dox) and radioactive agent (¹⁵³Sm) was successfully developed in this study. The formulation fulfilled all the desired physicochemical properties of a chemo-radioembolic agent and achieved better in vitro cytotoxicity on HepG2 cells. Further investigations are needed to evaluate the biosafety, radiation dosimetry, and synergetic anticancer properties of the formulation.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 10","pages":"308-320"},"PeriodicalIF":1.8,"publicationDate":"2023-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10007654","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":"Synthesis and evaluation of 111In-labeled tetrapeptide-based compounds as single-photon emission computed tomography imaging probes targeting granzyme B","authors":"Nobuki Kazuta,&nbsp;Hiroyuki Watanabe,&nbsp;Masahiro Ono","doi":"10.1002/jlcr.4045","DOIUrl":"https://doi.org/10.1002/jlcr.4045","url":null,"abstract":"<p>Granzyme B is an attractive target as a biomarker for contributing to improve the treatment with immune checkpoint inhibitor (ICI). In this study, we designed novel ¹¹¹In-labeled granzyme B-targeting single-photon emission computed tomography (SPECT) imaging probes, [¹¹¹In]IDT and [¹¹¹In]IDAT. Nonradioactive In-labeled granzyme B-targeting compounds ([^natIn]IDT, [^natIn]IDAT) showed the affinity for recombinant mouse granzyme B. [¹¹¹In]IDT and [¹¹¹In]IDAT were obtained with moderate radiochemical yield and high stability in mouse plasma (&gt;95%). In a biodistribution experiment using tumor-bearing mice, [¹¹¹In]IDT and [¹¹¹In]IDAT showed moderate accumulation in tumor. Ex vivo autoradiography (ARG) indicated that the accumulation of radioactivity in tumor was correlated to expression of granzyme B confirmed by the immunohistochemical staining. These results indicated that [¹¹¹In]IDT and [¹¹¹In]IDAT showed the basic properties as granzyme B-targeting SPECT probes.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 10","pages":"298-307"},"PeriodicalIF":1.8,"publicationDate":"2023-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50155621","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":"Efficient synthesis of carbon-14 labeled metabolites of the strobilurin fungicide mandestrobin using biomimetic iron-porphyrin catalyzed oxidation","authors":"Shuichi Murata,&nbsp;Motohiro Kurosawa,&nbsp;Takuo Fujisawa","doi":"10.1002/jlcr.4044","DOIUrl":"10.1002/jlcr.4044","url":null,"abstract":"Biomimetic oxidation using synthetic iron-porphyrin (F20 TPPFeCl) as a catalyst eliminated a xylene moiety of the fungicide mandestrobin, uniformly labeled with carbon-14 at the benzyl ring, to produce the corresponding radiolabeled metabolite 1. This reaction mechanism was investigated by identifying chemical structures of intermediate 5 and p-xyloquinone derivatives 6 and 7, as by-products. Optimization of reaction factors based on the mechanism improved the yield of 1 from mandestrobin up to 87%. Finally, various carbon-14 labeled metabolites of mandestrobin were prepared from 1.","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 10","pages":"290-297"},"PeriodicalIF":1.8,"publicationDate":"2023-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10385165","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":"Small-scale two-dimensional liquid chromatography for a preparative re-purification of a highly labile tritium-labeled compound","authors":"Martin Sandvoss,&nbsp;Christian Klaus,&nbsp;Remo Weck,&nbsp;Volker Derdau,&nbsp;Matthias Schiell","doi":"10.1002/jlcr.4028","DOIUrl":"10.1002/jlcr.4028","url":null,"abstract":"<p>Tritium-labeled compounds are generally less stable than their non-labeled counterparts. This requires storage at low temperatures, a constant workflow of quality checks, and subsequent re-purifications. As the amount of tritium-labeled material is typically purified in the μg range, repeated injections on analytical-scale ultra high-performance liquid chromatography systems can provide high-resolution re-purification results. Yet, degradants can be undesirably included in the compound isolation because the amount of decomposition can vary dramatically depending on the structure. We report a case of a sensitive molecule that could not be isolated in pure form even though the chromatographic separation was successful. In this case, the use of a small-scale two-dimensional preparative liquid chromatography approach with a direct transfer interface to a second (trapping) column resulted in a highly pure compound (&gt;98% radiochemical purity). This approach combines high chromatographic resolution, accurate control over the re-purification process, minimal sample manipulation, and higher overall safety for the handling of radioactive samples.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 7-8","pages":"189-197"},"PeriodicalIF":1.8,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9679256","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":"The inverse electron demand Diels–Alder cycloaddition with carbon-11 and fluorine-18: A gateway to pretargeted imaging across the blood–brain barrier","authors":"Simon H. Zientek,&nbsp;Stephen Thompson,&nbsp;Selena Milicevic Sephton,&nbsp;Franklin I. Aigbirhio","doi":"10.1002/jlcr.4029","DOIUrl":"10.1002/jlcr.4029","url":null,"abstract":"<p>There is increased focus on developing tools to image large biomolecules, such as antibodies, within the brain using positron emission tomography (PET). The inverse electron demand Diels–Alder cycloaddition (IEDDA) reaction has offered the greatest prospect of achieving such a feat and has gained much interest over the past decade. The fast reaction kinetics of the IEDDA reaction opens up the possibility of utilising a pretargeted approach, whereby the subject is pretreated with a biomolecule that has high specificity for its target. A radiolabelled second component is then administered to the subject, enabling the biomolecule to be visualised by PET. However, for this to become common practice, there is a need for the development of either radiolabelled <i>trans</i>-cyclooctenes (TCOs) or tetrazines that can cross the blood–brain barrier (BBB). This review highlights the advancements in the development of both radiolabelled TCOs and tetrazines, which have been radiolabelled with either carbon-11 or fluorine-18 and show promise or have been evaluated for use in pretargeted PET imaging across the BBB.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 9","pages":"249-268"},"PeriodicalIF":1.8,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851509","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":"Automated radiosynthesis of 1-(2-[18F]fluoroethyl)-L-tryptophan ([18F]FETrp) for positron emission tomography (PET) imaging of cancer in humans","authors":"Huailei Jiang,&nbsp;Yan Guo,&nbsp;Hancheng Cai,&nbsp;Nerissa Viola,&nbsp;Anthony Frank Shields,&nbsp;Otto Muzik,&nbsp;Csaba Juhasz","doi":"10.1002/jlcr.4027","DOIUrl":"https://doi.org/10.1002/jlcr.4027","url":null,"abstract":"<p>The radiotracer 1-(2-[¹⁸F]fluoroethyl)-L-tryptophan (L-[¹⁸F]FETrp or [¹⁸F]FETrp) is a substrate of indoleamine 2,3-dioxygenase, the initial and key enzyme of the kynurenine pathway associated with tumoral immune resistance. In preclinical positron emission tomography studies, [¹⁸F]FETrp is highly accumulated in a wide range of primary and metastatic cancers, such as lung cancer, prostate cancer, and gliomas. However, the clinical translation of this radiotracer into the first-in-human trial has not been reported, partially due to its racemization during radiofluorination which renders the purification of the final product challenging. However, efficient purification is essential for human studies in order to assure radiochemical and enantiomeric purity. In this work, we report a fully automated radiosynthesis of [¹⁸F]FETrp on a Synthra RNPlus research module, including a one-pot two steps radiosynthesis, dual independent chiral and reverse-phase semipreparative high-performance liquid chromatography purifications, and solid-phase extraction-assisted formulation. The presented approach has led to its Investigational New Drug application and approval that allows the testing of this tracer in humans.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 7-8","pages":"180-188"},"PeriodicalIF":1.8,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50146522","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":"Nitrilase mediated mild hydrolysis of a carbon-14 nitrile for the radiosynthesis of 4-(7-hydroxycarbamoyl-[1-14C-heptanoyl]-oxy)-benzoic acid methyl ester, [14C]-SHP-141: A novel class I/II histone deacetylase (HDAC) inhibitor","authors":"Sean L. Kitson,&nbsp;William Watters,&nbsp;Thomas S. Moody,&nbsp;Todd Chappell,&nbsp;Ralph Mazitschek","doi":"10.1002/jlcr.4026","DOIUrl":"https://doi.org/10.1002/jlcr.4026","url":null,"abstract":"<p>A strategy has been developed for the carbon-14 radiosynthesis of <b>[</b>^<b>14</b><b>C]-SHP-141</b>, a 4-(7-hydroxycarbamoyl-heptanoyloxy)-benzoic acid methyl ester derivative containing a terminal hydroxamic acid. The synthesis involved four radiochemical transformations. The key step in the radiosynthesis was the conversion of the 7-[¹⁴C]-cyano-heptanoic acid benzyloxyamide <b>[</b>^<b>14</b><b>C]-4</b> directly into the carboxylic acid derivative, 7-benzyloxycarbamoyl-[¹⁴C]-heptanoic acid <b>[</b>^<b>14</b><b>C]-8</b> using nitrilase-113 biocatalyst. The final step involved deprotection of the benzyloxy group using catalytic hydrogenation to facilitate the release of the hydroxamic acid without cleaving the phenoxy ester. <b>[</b>^<b>14</b><b>C]-SHP-141</b> was isolated with a radiochemical purity of 90% and a specific activity of 190 μCi/mg from four radiochemical steps starting from potassium [¹⁴C]-cyanide in a radiochemical yield of 45%.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 7-8","pages":"172-179"},"PeriodicalIF":1.8,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50143125","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":"RO6807936 as a novel positron emission tomography (PET) radiotracer for in vitro and in vivo visualization and quantification of beta-site amyloid precursor protein cleaving enzyme (BACE1) in the rodent and baboon brain","authors":"Michael Honer,&nbsp;Alessandra Polara,&nbsp;Hiroto Kuwabara,&nbsp;Helmut Jacobsen,&nbsp;Axel Pähler,&nbsp;Thomas Hartung,&nbsp;Antonello Caruso,&nbsp;Daria Esterhazy,&nbsp;Markus Stoffel,&nbsp;Robert F. Dannals,&nbsp;Dean F. Wong,&nbsp;Edilio Borroni,&nbsp;Luca C. Gobbi","doi":"10.1002/jlcr.4025","DOIUrl":"10.1002/jlcr.4025","url":null,"abstract":"<p>The beta-site amyloid precursor protein cleaving enzyme (BACE1) is responsible for initiating the generation of beta-amyloid, the major constituent of amyloid plaques in Alzheimer's disease (AD). The purpose of this study was to develop a specific BACE1 radioligand for visualization of the distribution pattern and quantification of the BACE1 protein in the rodent and monkey brain both in vitro by autoradiography and in vivo by positron emission tomography (PET). The BACE1 inhibitor RO6807936 originating from an in-house chemical drug optimization program was selected based on its PET tracer-like physicochemical properties and a favorable pharmacokinetic profile. Saturation binding analysis of [³H]RO6807936 revealed specific and high-affinity binding (<i>K</i>_<i>D</i> = 2.9 nM) and a low <i>B</i>_max value (4.3 nM) of the BACE1 protein in native rat brain membranes. [³H]RO6807936 binding showed a ubiquitous distribution on rat brain slices in vitro with higher levels in the CA3 pyramidal cell layer and the granule cell layer of the hippocampus. In a next step, RO6807936 was successfully radiolabeled with carbon-11 and showed acceptable uptake in the baboon brain as well as a widespread and rather homogeneous distribution consistent with rodent data. In vivo blockade studies with a specific BACE1 inhibitor reduced uptake of the tracer to homogenous levels across brain regions and demonstrated specificity of the signal. Our data warrant further profiling of this PET tracer candidate in humans to investigate BACE1 expression in normal individuals and those with AD and as an imaging biomarker for target occupancy studies in clinical drug trials.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 9","pages":"222-236"},"PeriodicalIF":1.8,"publicationDate":"2023-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9881807","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":"Synthesis of BI 894416 and BI 1342561, two potent and selective spleen tyrosine kinase inhibitors, labeled with carbon 14 and with deuterium","authors":"Bachir Latli,&nbsp;Matt J. Hrapchak,&nbsp;Lalith P. Samankumara,&nbsp;Daniel R. Fandrick,&nbsp;Scott Pennino,&nbsp;Heewon Lee,&nbsp;Jinhua J. Song","doi":"10.1002/jlcr.4024","DOIUrl":"10.1002/jlcr.4024","url":null,"abstract":"<p>(<i>R</i>)-4-((<i>R</i>)-1-((6-(1-[<i>tert-</i>butyl]-1<i>H</i>-pyrazol-4-yl)-2-methyl-2<i>H</i>-pyrazolo[3,4-d]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one (<b>BI 894416</b>, <b>1</b>) and (<i>R</i>)-4-((<i>R</i>)-1-((6-(1-[<i>tert</i>-butyl]-1<i>H</i>-pyrazol-4-yl)-2,3-dimethyl-2<i>H</i>-indazol-4-yl)oxy)ethyl)pyrrolidin-2-one (<b>BI 1342561</b>, <b>2</b>) are two new potent and selective spleen tyrosine kinase inhibitors developed to treat severe asthma. Both compounds have similar structures and they differ only in the bicyclic moiety 2-methyl-2<i>H</i>-pyrazolo[4,3-c]pyridine in <b>1</b> versus 2,3-dimethyl-2<i>H</i>-indazole in <b>2</b>. In the carbon 14 synthesis, 1-(1-[<i>tert</i>-butyl]-1<i>H</i>-pyrazol-4-yl)ethan-1-one-1-¹⁴<i>C</i> (<b>[</b>^<b>14</b><b>C]-8</b>) was prepared from the cyanation of 4-bromopyrazole using zinc [¹⁴C]cyanide followed by methyl lithium addition on the nitrile group. The enolate of <b>[</b>^<b>14</b><b>C]-8</b> was then used to access these two bicyclic moieties via pyrano-pyrazoles <b>[</b>^<b>14</b><b>C]-11</b> and <b>[</b>^<b>14</b><b>C]-12</b>, which were further transformed in few more steps to <b>[</b>^<b>14</b><b>C]-(1)</b> and <b>[</b>^<b>14</b><b>C]-2</b>. Both inhibitors contain a <i>tert-</i>butyl group. Introducing <i>tert-</i>butyl-<i>d</i>₉ will not only provide internal standards for bioanalytical studies, but it is also expected to slow down the metabolism of these two compounds. Most of the metabolites of compound <b>1</b>, for example, are the result of <i>tert</i>-butyl oxidation, like alcohol <b>3</b>, acid <b>4</b>, and the further <i>N</i>-demethylation of <b>4</b> to <b>5</b>. The detailed preparation of these deuterium-labeled metabolites is also described.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 4-6","pages":"155-168"},"PeriodicalIF":1.8,"publicationDate":"2023-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9672939","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":"Peptides for trans-blood–brain barrier delivery","authors":"Reuben Blades,&nbsp;Lars M. Ittner,&nbsp;Ole Tietz","doi":"10.1002/jlcr.4023","DOIUrl":"10.1002/jlcr.4023","url":null,"abstract":"<p>Trans-blood–brain barrier (BBB) delivery of therapeutic and diagnostic agents is a major challenge in the development of central nervous system (CNS) targeted radiopharmaceuticals. This review is an introduction to the use of peptides as delivery agents to transport cargos into the CNS. The most widely used BBB-penetrating peptides are reviewed here, with a particular emphasis on the broad range of cargos delivered into the CNS using these. Cell-penetrating peptides (CPPs) have been deployed as trans-BBB delivery agents for some time; new developments in the CPP field offer exciting opportunities for the design of next generation trans-BBB complexes. Many of the peptides highlighted here are ready to be combined with diagnostic and therapeutic radiopharmaceuticals to develop highly effective CNS-targeted agents.</p>","PeriodicalId":16288,"journal":{"name":"Journal of labelled compounds & radiopharmaceuticals","volume":"66 9","pages":"237-248"},"PeriodicalIF":1.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jlcr.4023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9896270","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}