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Molecular MRI and PET methods for detection of transplanted stem cells and cancer.

机译：分子MRI和PET方法用于检测移植的干细胞和癌症。

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摘要

Stem cell therapies hold great potential for treatment of neurodegenerative diseases. In this setting, the inability to monitor grafted cell dynamics in the central nervous system limits understanding of cell fates underlying therapeutic response, making therapy design and optimization significantly more challenging. To address this limitation, we aim to design, evaluate, and develop new imaging approaches for detection of human stem cells in vivo. Over-expression of the manganese transporter protein DMT1 in human neural progenitor cells (hNPC) significantly increases intracellular accumulation of the T1-shortening agent Mn2+ and the novel positron emitter 52Mn2+. This work addresses three specific hypotheses: (1) hNPC over-expressing DMT1 are suitable for in vivo cellular imaging, (2) in vivo 52 Mn PET and manganese-enhanced MRI are applicable for cell tracking in the rat brain, and (3) Mn-based imaging can be used to detect grafted stem cells in vivo. In addition, we apply the techniques and knowledge developed for stem cell tracking to the characterization and initial in vivo testing of a novel cancer-targeted MRI contrast agent, Gd-DO3A-404. The results of this work establish both the potential and limitations of this approach for in vivo cell tracking. In particular, we find that hNPC transiently over-expressing DMT1 are most suitable for in vivo detection following transplantation. Additionally, the methods for quantitative MRI, 52Mn PET, and cancer-targeted contrast-enhanced MRI developed in this work contribute more broadly to the fields of molecular MRI and multi-modality imaging.
机译：干细胞疗法在治疗神经退行性疾病方面具有巨大潜力。在这种情况下，无法监控中枢神经系统中移植的细胞动力学会限制对潜在治疗反应的细胞命运的了解，从而使治疗设计和优化变得更具挑战性。为了解决这一局限性，我们旨在设计，评估和开发用于在体内检测人干细胞的新成像方法。锰转运蛋白DMT1在人类神经祖细胞（hNPC）中的过表达显着增加了T1缩短剂Mn2 +和新型正电子发射体52Mn2 +的细胞内积累。这项工作针对三个特定的假设：（1）hNPC过表达的DMT1适用于体内细胞成像，（2）体内52 Mn PET和锰增强MRI适用于大鼠脑中的细胞追踪，以及（3）基于锰的成像可用于检测体内移植的干细胞。此外，我们将为干细胞追踪开发的技术和知识应用于新型靶向癌症的MRI造影剂Gd-DO3A-404的表征和初始体内测试。这项工作的结果确立了这种方法在体内细胞追踪中的潜力和局限性。特别是，我们发现hNPC瞬时过表达DMT1最适合移植后的体内检测。此外，这项工作中开发的定量MRI，52Mn PET和以癌症为目标的对比增强MRI的方法在分子MRI和多模态成像领域做出了更广泛的贡献。

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  • 作者

    Brunnquell, Christina L.;

  • 作者单位

    The University of Wisconsin - Madison.;

  • 授予单位 The University of Wisconsin - Madison.;
  • 学科 Medical imaging.;Neurosciences.
  • 学位 Ph.D.
  • 年度 2016
  • 页码 187 p.
  • 总页数 187
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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