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正电子发射断层显像剂3'-脱氧-3'-[18F]氟胸苷([18F]FLT)不适用于检测小鼠全身性小肠结肠炎耶尔森菌感染诱导的组织增殖。

The Positron Emission Tomography Tracer 3'-Deoxy-3'-[18F]Fluorothymidine ([18F]FLT) Is Not Suitable to Detect Tissue Proliferation Induced by Systemic Yersinia enterocolitica Infection in Mice.

作者信息

Wiehr Stefan, Rolle Anna-Maria, Warnke Philipp, Kohlhofer Ursula, Quintanilla-Martinez Leticia, Reischl Gerald, Autenrieth Ingo B, Pichler Bernd J, Autenrieth Stella E

机构信息

Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.

Institute of Medical Microbiology and Hygiene, Eberhard Karls University Tübingen, Tübingen, Germany.

出版信息

PLoS One. 2016 Oct 4;11(10):e0164163. doi: 10.1371/journal.pone.0164163. eCollection 2016.

Abstract

Most frequently, gram-negative bacterial infections in humans are caused by Enterobacteriaceae and remain a major challenge in medical diagnostics. We non-invasively imaged moderate and severe systemic Yersinia enterocolitica infections in mice using the positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), which is a marker of proliferation, and compared the in vivo results to the ex vivo biodistributions, bacterial loads, and histologies of the corresponding organs. Y. enterocolitica infection is detectable with histology using H&E staining and immunohistochemistry for Ki 67. [18F]FLT revealed only background uptake in the spleen, which is the main manifestation site of systemic Y. enterocolitica-infected mice. The uptake was independent of the infection dose. Antibody-based thymidine kinase 1 (Tk-1) staining confirmed the negative [18F]FLT-PET data. Histological alterations of spleen tissue, observed via Ki 67-antibody-based staining, can not be detected by [18F]FLT-PET in this model. Thus, the proliferation marker [18F]FLT is not a suitable tracer for the diagnosis of systemic Y. enterocolitica infection in the C57BL/6 animal model of yersiniosis.

摘要

在人类中,革兰氏阴性菌感染最常见的是由肠杆菌科细菌引起的,这仍然是医学诊断中的一项重大挑战。我们使用正电子发射断层扫描(PET)示踪剂3'-脱氧-3'-[18F]氟胸苷([18F]FLT)对小鼠中度和重度全身性小肠结肠炎耶尔森菌感染进行了无创成像,[18F]FLT是一种增殖标志物,并将体内结果与相应器官的体外生物分布、细菌载量和组织学进行了比较。使用苏木精和伊红(H&E)染色以及针对Ki 67的免疫组织化学,通过组织学可检测到小肠结肠炎耶尔森菌感染。[18F]FLT在脾脏中仅显示本底摄取,脾脏是全身性小肠结肠炎耶尔森菌感染小鼠的主要表现部位。摄取与感染剂量无关。基于抗体的胸苷激酶1(Tk-1)染色证实了[18F]FLT-PET的阴性数据。在该模型中,通过基于Ki 67抗体的染色观察到的脾脏组织学改变无法通过[18F]FLT-PET检测到。因此,增殖标志物[18F]FLT不是耶尔森菌病C57BL/6动物模型中全身性小肠结肠炎耶尔森菌感染诊断的合适示踪剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9d4/5049782/4a837cf90382/pone.0164163.g001.jpg

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