Imaging tracers for cell tracking applications with magnetic resonance imaging (MRI) and positron emission tomography (PET)

越来越多的新兴医学诊断和治疗程序需要在体内跟踪细胞。为了监测和量化基因治疗、朗格汉斯胰岛植入（治疗糖尿病）或干细胞治疗方法中使用的细胞的命运，有必要使用磁共振成像（MRI）。核磁共振成像现在在大多数中型和大型医疗机构中植入得很好。它是可访问的，并提供图像的解剖分辨率不使用电离辐射。为了在体内观察细胞，必须用铁、钆或锰元素制成的磁成像探针标记细胞。这些示踪剂要么“增强”要么“减弱”MRI信号，以显示标记细胞的存在。在这项研究计划中，新的Gd2O3和MnO将被开发出来，这将使更多的定量，更高分辨率的细胞跟踪研究成为可能。创新的纳米颗粒表面处理将被开发出来，以防止颗粒在恶劣的流体环境中降解。然后，为了更精确和更精细地定义少量标记细胞的存在，并加强全身细胞跟踪的定量方面，磁性和放射性纳米粒子将被开发出来。为此，正电子发射器（放射性同位素）将被用于“掺杂”或“标记”磁性纳米粒子。在所有全身成像方式中，正电子发射断层扫描允许最高的检测灵敏度。随着最近双PET/MRI扫描仪的商业化，它可以将高分辨率的MRI与高灵敏度的PET耦合起来，本研究计划中开发的新型“PET/MRI”示踪剂将允许更多的定量细胞跟踪研究。最后，研究计划提案的一个方面涉及PET/MRI示踪合成器的开发，这是一种可以直接安装在诊所和实验室的小型设备。

A growing number of emerging medical diagnostics and therapeutic procedures require the tracking of cells in vivo. In order to monitor and to quantify the fate of cells used in novel procedures for gene therapies, for Langerhans islet implantation (to cure diabetes), or for stem cell therapeutic approaches, it is necessary to use magnetic resonance imaging (MRI). MRI is now very well implanted in a majority of mid- and large-scale medical facilities. It is accessible and provides images of anatomical resolution without the use of ionising radiation. In order to visualise cells in vivo, the cells must be labelled with magnetic imaging probes made of the elements Fe, Gd, or Mn. These tracers either "enhance" or "decrease" the MRI signal to reveal the presence of labelled cells. In this research proposal, new Gd2O3 and MnO will be developed that will enable more quantitative, higher resolution cell tracking studies. Innovative nanoparticle surface treatments will be developed to prevent the degradation of particles submitted to harsh fluid environments. Then, to more precisely and more finely define the presence of small amounts of labelled cells, and to enhance the quantitative aspects of whole-body cell tracking, magnetic and radioactive nanoparticles will be developed. For this purpose, positron emitters (radioisotopes) will be used to "dope" or to "label" magnetic nanoparticles. Of all whole-body imaging modalities, positron emission tomography allows for the highest detection sensitivity. With the recent commercialization of dual PET/MRI scanners, which enable the coupling of high-resolution MRI with high-sensitivity PET, the new "PET/MRI" tracers developed in this research proposal will allow for more quantitative cell tracking studies. Finally, one aspect of the research program proposal addresses the development of a PET/MRI tracer synthesizer, a small equipment that may be advantageously installed directly in clinics and laboratories.