Antonio Esposito MD, Presenter: Nothing to Disclose

Francesco Aldo De Cobelli MD, Abstract Co-Author: Nothing to Disclose

Paola Maffi, Abstract Co-Author: Nothing to Disclose

Maria Luisa Malosio, Abstract Co-Author: Nothing to Disclose

Antonio Secchi, Abstract Co-Author: Nothing to Disclose

Alessandro Del Maschio MD, Abstract Co-Author: Nothing to Disclose

Non-invasive islets fate monitoring is crucial to improve clinical management of islets-tx. Aims were to standardize the procedure of islets labeling with iron, to prove the labeling safety and effectiveness for MRI visualization after islet-tx in mice and to translate the developed imaging approach from mice to patients correlating the graft function with the imaging results.

Human and murine islets were labeled by incubation with different concentration of Endorem®(112-1120µg/ml). Viability, functionality, inflammatory status and susceptibility to inflammatory cytokines of labeled-islets were assessed in vitro. Murine labeled-islets were transplanted by portal-vein infusion into syngeneic diabetic mice and followed with 1.5T and 7T MRI. Recently, three patients were transplanted with labeled-islets and underwent 1.5T MRI at 1, 2, 3, 7 days and every month, after transplantation.

The ratio Endorem®/islets resulted crucial for reproducible labeling; 2.24µg/IEQ-ratio allowed successful in-vivo islets imaging in mice. Viability, function, inflammation and susceptibility to inflammation were not different between labeled and unlabeled islets. Labeled-islets reverted diabetes in mice. Transplanted labeled-islets were clearly visible as hypointense spot scattered into the liver of the three patients at post-transplantation MRI. One patient showed complete loss of spots during the first month follow-up, associated with complete failure of graft function. Second and third patients showed an important loss of spots during the first days and the first month (respectively 60% and 80% loss at 1 month control) followed by a very slow progressive disappearance of islets in subsequent months, associated with a discrete graft function persistence. Currently, the MRI follow-up arrived at three months with the respective persistence of 22% and 13% of spots.

MRI monitoring of islets-tx is feasible and safe in humans. The correlation of graft function with imaging results in humans allows to visualize the previously supposed phenomenon of loss of most of islets in the first phases after transplantation, demonstrating that a small amount of islets maintains the graft function.

The presented imaging approach is useful in the follow-up of clinical pancreatic islets transplantation.

Esposito, A, De Cobelli, F, Maffi, P, Malosio, M, Secchi, A, Del Maschio, A, Magnetic Resonance Imaging (MRI) of Iron Labeled Pancreatic Islets Transplantation (Islets-tx): From Preclinical Setting to Clinical Application.  Radiological Society of North America 2010 Scientific Assembly and Annual Meeting, November 28 - December 3, 2010 ,Chicago IL. http://archive.rsna.org/2010/9014799.html