Evgenov Natalia V, Medarova Zdravka, Pratt John, Pantazopoulos Pamela, Leyting Simone, Bonner-Weir Susan, Moore Anna
Molecular Imaging Laboratory, Department of Radiology, Massachusetts General Hospital/Massachusetts Institute of Technology/Harvard Medical School, Charlestown, MA 02129, USA.
Diabetes. 2006 Sep;55(9):2419-28. doi: 10.2337/db06-0484.
As islet transplantation becomes an acceptable clinical modality for restoring normoglycemia in type 1 diabetic patients, there is a crucial need for noninvasive assessment of the fate of the grafts. In spite of the success of the Edmonton Protocol, a significant graft loss occurs due to immunological and nonimmunological events immediately after transplantation. Allogeneic rejection in graft recipients is one of the major reasons for islet death and graft failure. Therefore, monitoring the islet rejection using reliable noninvasive methods would significantly aid in clinical assessment of graft success. We have previously developed a method to detect transplanted islets noninvasively using magnetic resonance imaging (MRI). For this procedure, human pancreatic islets are labeled with an MRI contrast agent that enables their visualization on magnetic resonance images. In our present study, we not only detected labeled human islets in a preclinical intrahepatic model of human islet transplantation in mice but also showed that islet rejection can be monitored noninvasively and repeatedly in real time by MRI. In addition, in this study, we have adapted, for islet cell labeling, a Food and Drug Administration-approved commercially available contrast agent, Feridex, that is used clinically for liver imaging. We believe that this agent, in combination with our preclinical model of islet transplantation, will facilitate the transition of imaging immune rejection to clinical trials.
随着胰岛移植成为恢复1型糖尿病患者正常血糖水平的一种可接受的临床方式，对移植物命运进行非侵入性评估的需求至关重要。尽管埃德蒙顿方案取得了成功，但移植后立即发生的免疫和非免疫事件导致了大量移植物丢失。移植物受者的同种异体排斥是胰岛死亡和移植物失败的主要原因之一。因此，使用可靠的非侵入性方法监测胰岛排斥将极大地有助于临床评估移植物的成功。我们之前开发了一种使用磁共振成像（MRI）非侵入性检测移植胰岛的方法。对于该程序，人胰岛用MRI造影剂标记，使其能够在磁共振图像上可视化。在我们目前的研究中，我们不仅在小鼠人胰岛移植的临床前肝内模型中检测到了标记的人胰岛，还表明MRI可以实时、非侵入性且反复地监测胰岛排斥。此外，在本研究中，我们采用了一种经美国食品药品监督管理局批准的市售造影剂Feridex进行胰岛细胞标记，该造影剂临床上用于肝脏成像。我们相信，这种造影剂与我们的胰岛移植临床前模型相结合，将有助于将免疫排斥成像过渡到临床试验。
