Molecular Imaging of Pancreatic Islet Transplantation

Abstract

Islet replacement therapy, pancreatic islet transplantation, is considered as a potential option for curing T1DM. However, the significant loss of implanted islets after islet transplantation prevents it from becoming a mainstream treatment modality. Due to the lack of reliable noninvasive real-time imaging techniques to track the survival of the islets, it is impossible to discover the specific causes for the loss of implanted islets, not to mention taking interventions in the early stage. Current achievements in molecular imaging has provided with several promising techniques, including optical imaging, PET and MRI, for noninvasive visualization, quantification and functional evaluation of transplanted islets in experimental conditions. Optical imaging seems to be the most convenient and cost-efficient modality, but the limited penetration distance hinders its application in large animal and human studies. PET combined with target-specific tracers is characterized by high specificity and sensitivity for detection of islet grafts, but observation time is rather short (i.e., several hours). MRI stands out for its long-term visualization of transplanted islet grafts with the aid of contrast agents. However, quantification of islets remains a problem to be solved. A novel technique, microencapsulation, provides a new perspective in multimodal imaging by optimizing the strengths of several modalities together. Although the application of molecular imaging in clinical settings is still limited, significant success and valuable information is achieved in the basic and clinical trials. However, islet transplantation still remains an experimental procedure, with ongoing researches focusing on islets availability, appropriate sites for implantation, new methods using biomaterials (e.g. microencapsulation), immune modulation and more.

<p>Islet Transplantation Imaging in vivo</p>

“…Fourth, many factors may cause loss of SPIO signal in transplanted islet cells, eg, immune rejection, ischemia and inflammation in the liver after islets transplantation. 6,13,14 SPIO-labeled islets are more suitable for real-time imaging of transplanted islets. 15 Although Resovist is approved for clinical use as a liver-imaging agent 16 and it has been proved that porcine islets can safely and efficiently be labeled with Resovist to monitor kidney capsules of diabetic mice ( Figure 1A), 17 it has not been applied further because of its instability in clinical trials.…”

“…Fourth, many factors may cause loss of SPIO signal in transplanted islet cells, eg, immune rejection, ischemia and inflammation in the liver after islets transplantation. 6 , 13 , 14 SPIO-labeled islets are more suitable for real-time imaging of transplanted islets. 15 …”

“…Transplanted islets can be quantified using fluorine-19 ( 19 F) under MRI due to lack of endogenous fluoride in the body 13 and the high specificity of 19 F. It has been reported that 19 F has no effect on islet cell viability and function. 23 Barnett et al found that transplanted human cadaveric islets labeled with rhodamine-perfluorooctylbromide (PFOB) nanoparticles can be viewed by 19 F MRI under the kidney capsules of mice and rabbits.…”

Transplantation technologies for treatment of carbohydrate metabolism disorders

“…С помощью позитронно-эмиссионной томографии установлено, что сразу после внутрипортального введения 50-70% островков теряет жизнеспособность. Поэтому необходимо использование взвеси от 2-3 доноров [25,26].…”

Molecular imaging of β-cells: diabetes and beyond

“…In the last few years, islet transplantation has arisen as a treatment alternative for T1DM. To visualize transplanted islets and monitor their fate, various noninvasive probes and functionalized nanoparticles have been investigated and significant success has been achieved in basic trials to date [171][172][173]. The first successful in vivo imaging and detection of transplanted islets was reported by Lu et al in 2004, wherein the authors transfected islets with a recombinant adenovirus coding for the luciferase gene and demonstrated that introduction of reporter gene-directed luciferase expression into the isolated islets allowed the long-term monitoring of grafted islets [174].…”