MR imaging monitoring of iron-labeled pancreatic islets in a small series of patients: Islet fate in successful, unsuccessful, and autotransplantation

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Abstract

Islet transplantation is one of the most promising and effective therapies for restoring normoglycemia in type 1 diabetes (T1D) patients, but islet engraftment is one of the main obstacles hampering long-term success. Monitoring graft loss, caused either by immunological or nonimmunological events, occurring in the first phase after transplantation and at later stages of a patient’s life is a very important issue. Among the imaging approaches previously applied, magnetic resonance imaging (MRI) monitoring of islet fate following labeling with superparamagnetic iron oxide agents yielded promising results. The aim of this study was to translate into patients the method of islet labeling and MRI monitoring developed in our preclinical setting and to compare imaging results with graft clinical outcome. Three T1D patients and one nondiabetic patient undergoing autotransplantation following subtotal pancreatectomy received Endorem®-labeled islets. Patients were monitored by MRI and metabolically (HbA1c, exogenous insulin requirement, and C-peptide, TEF) at 1, 3, and 7 days following transplantation and once a month up to 10 months. Labeled transplanted islets appeared as hypointense areas scattered within the liver parenchyma, whose absolute number at 24 h after transplantation reflected the labeling efficiency. In patients #1 and #3 with good midterm graft function, MRI follow-up showed an important early loss of hypointense spots followed by a slow and progressive disappearance at later timepoints. Graft loss of function in patient #2 4 weeks after transplantation was associated with the complete disappearance of all hypointense signals. The autotransplanted patient, stably insulin free, showed no significant signal reduction during the first 3 days, followed by loss of spots similar to a patient with good midterm graft function. These results suggest that MRI monitoring of islet transplantation at early time points could represent a meaningful readout for helping in predicting transplant failure or success, but its relevance for mid/long-term islet function assessment appears evanescent.

Original languageEnglish
Pages (from-to)2285-2296
Number of pages12
JournalCell Transplantation
Volume24
Issue number11
DOIs
Publication statusPublished - 2015

Fingerprint

Autologous Transplantation
Islets of Langerhans
Iron
Magnetic resonance
Grafts
Imaging techniques
Monitoring
Transplants
Labeling
Magnetic Resonance Imaging
Insulin
Transplantation
Medical problems
Islets of Langerhans Transplantation
Type 1 Diabetes Mellitus
Iron oxides
Liver
Peptides
Pancreatectomy
C-Peptide

Keywords

  • Autoimmunity
  • Autologous islet transplantation
  • Cytokines
  • Inflammation
  • Magnetic resonance imaging (MRI)
  • Pancreatic islet transplantation
  • Superparamagnetic iron oxide particles (SPIO)
  • Type 1 diabetes patients

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

@article{15000c81ab2643258a4865fb30679b3a,
title = "MR imaging monitoring of iron-labeled pancreatic islets in a small series of patients: Islet fate in successful, unsuccessful, and autotransplantation",
abstract = "Islet transplantation is one of the most promising and effective therapies for restoring normoglycemia in type 1 diabetes (T1D) patients, but islet engraftment is one of the main obstacles hampering long-term success. Monitoring graft loss, caused either by immunological or nonimmunological events, occurring in the first phase after transplantation and at later stages of a patient’s life is a very important issue. Among the imaging approaches previously applied, magnetic resonance imaging (MRI) monitoring of islet fate following labeling with superparamagnetic iron oxide agents yielded promising results. The aim of this study was to translate into patients the method of islet labeling and MRI monitoring developed in our preclinical setting and to compare imaging results with graft clinical outcome. Three T1D patients and one nondiabetic patient undergoing autotransplantation following subtotal pancreatectomy received Endorem{\circledR}-labeled islets. Patients were monitored by MRI and metabolically (HbA1c, exogenous insulin requirement, and C-peptide, TEF) at 1, 3, and 7 days following transplantation and once a month up to 10 months. Labeled transplanted islets appeared as hypointense areas scattered within the liver parenchyma, whose absolute number at 24 h after transplantation reflected the labeling efficiency. In patients #1 and #3 with good midterm graft function, MRI follow-up showed an important early loss of hypointense spots followed by a slow and progressive disappearance at later timepoints. Graft loss of function in patient #2 4 weeks after transplantation was associated with the complete disappearance of all hypointense signals. The autotransplanted patient, stably insulin free, showed no significant signal reduction during the first 3 days, followed by loss of spots similar to a patient with good midterm graft function. These results suggest that MRI monitoring of islet transplantation at early time points could represent a meaningful readout for helping in predicting transplant failure or success, but its relevance for mid/long-term islet function assessment appears evanescent.",
keywords = "Autoimmunity, Autologous islet transplantation, Cytokines, Inflammation, Magnetic resonance imaging (MRI), Pancreatic islet transplantation, Superparamagnetic iron oxide particles (SPIO), Type 1 diabetes patients",
author = "Malosio, {Maria Luisa} and Antonio Esposito and Cristina Brigatti and Anna Palmisano and Lorenzo Piemonti and Rita Nano and Paola Maffi and Cobelli, {Francesco De} and Maschio, {Alessandro Del} and Antonio Secchi",
year = "2015",
doi = "10.3727/096368914X684060",
language = "English",
volume = "24",
pages = "2285--2296",
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T1 - MR imaging monitoring of iron-labeled pancreatic islets in a small series of patients

T2 - Islet fate in successful, unsuccessful, and autotransplantation

AU - Malosio, Maria Luisa

AU - Esposito, Antonio

AU - Brigatti, Cristina

AU - Palmisano, Anna

AU - Piemonti, Lorenzo

AU - Nano, Rita

AU - Maffi, Paola

AU - Cobelli, Francesco De

AU - Maschio, Alessandro Del

AU - Secchi, Antonio

PY - 2015

Y1 - 2015

N2 - Islet transplantation is one of the most promising and effective therapies for restoring normoglycemia in type 1 diabetes (T1D) patients, but islet engraftment is one of the main obstacles hampering long-term success. Monitoring graft loss, caused either by immunological or nonimmunological events, occurring in the first phase after transplantation and at later stages of a patient’s life is a very important issue. Among the imaging approaches previously applied, magnetic resonance imaging (MRI) monitoring of islet fate following labeling with superparamagnetic iron oxide agents yielded promising results. The aim of this study was to translate into patients the method of islet labeling and MRI monitoring developed in our preclinical setting and to compare imaging results with graft clinical outcome. Three T1D patients and one nondiabetic patient undergoing autotransplantation following subtotal pancreatectomy received Endorem®-labeled islets. Patients were monitored by MRI and metabolically (HbA1c, exogenous insulin requirement, and C-peptide, TEF) at 1, 3, and 7 days following transplantation and once a month up to 10 months. Labeled transplanted islets appeared as hypointense areas scattered within the liver parenchyma, whose absolute number at 24 h after transplantation reflected the labeling efficiency. In patients #1 and #3 with good midterm graft function, MRI follow-up showed an important early loss of hypointense spots followed by a slow and progressive disappearance at later timepoints. Graft loss of function in patient #2 4 weeks after transplantation was associated with the complete disappearance of all hypointense signals. The autotransplanted patient, stably insulin free, showed no significant signal reduction during the first 3 days, followed by loss of spots similar to a patient with good midterm graft function. These results suggest that MRI monitoring of islet transplantation at early time points could represent a meaningful readout for helping in predicting transplant failure or success, but its relevance for mid/long-term islet function assessment appears evanescent.

AB - Islet transplantation is one of the most promising and effective therapies for restoring normoglycemia in type 1 diabetes (T1D) patients, but islet engraftment is one of the main obstacles hampering long-term success. Monitoring graft loss, caused either by immunological or nonimmunological events, occurring in the first phase after transplantation and at later stages of a patient’s life is a very important issue. Among the imaging approaches previously applied, magnetic resonance imaging (MRI) monitoring of islet fate following labeling with superparamagnetic iron oxide agents yielded promising results. The aim of this study was to translate into patients the method of islet labeling and MRI monitoring developed in our preclinical setting and to compare imaging results with graft clinical outcome. Three T1D patients and one nondiabetic patient undergoing autotransplantation following subtotal pancreatectomy received Endorem®-labeled islets. Patients were monitored by MRI and metabolically (HbA1c, exogenous insulin requirement, and C-peptide, TEF) at 1, 3, and 7 days following transplantation and once a month up to 10 months. Labeled transplanted islets appeared as hypointense areas scattered within the liver parenchyma, whose absolute number at 24 h after transplantation reflected the labeling efficiency. In patients #1 and #3 with good midterm graft function, MRI follow-up showed an important early loss of hypointense spots followed by a slow and progressive disappearance at later timepoints. Graft loss of function in patient #2 4 weeks after transplantation was associated with the complete disappearance of all hypointense signals. The autotransplanted patient, stably insulin free, showed no significant signal reduction during the first 3 days, followed by loss of spots similar to a patient with good midterm graft function. These results suggest that MRI monitoring of islet transplantation at early time points could represent a meaningful readout for helping in predicting transplant failure or success, but its relevance for mid/long-term islet function assessment appears evanescent.

KW - Autoimmunity

KW - Autologous islet transplantation

KW - Cytokines

KW - Inflammation

KW - Magnetic resonance imaging (MRI)

KW - Pancreatic islet transplantation

KW - Superparamagnetic iron oxide particles (SPIO)

KW - Type 1 diabetes patients

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