Magnetic particle imaging of islet transplantation in the liver and under the kidney capsule in mouse models

Abstract

Background: Islet transplantation (Tx) represents the most promising therapy to restore normoglycemia in type 1 diabetes (T1D) patients to date. As significant islet loss has been observed after the procedure, there is an urgent need for developing strategies for monitoring transplanted islet grafts. In this report we describe for the first time the application of magnetic particle imaging (MPI) for monitoring transplanted islets in the liver and under the kidney capsule in experimental animals.Methods: Pancreatic islets isolated from Papio hamadryas were labeled with superparamagnetic iron oxides (SPIOs) and used for either islet phantoms or Tx in the liver or under the kidney capsule of NOD scid mice.MPI was used to image and quantify islet phantoms and islet transplanted experimental animals post-mortem at 1 and 14 days after Tx. Magnetic resonance imaging (MRI) was used to confirm the presence of labeled islets in the liver and under the kidney capsule 1 day after Tx.Results: MPI of labeled islet phantoms confirmed linear correlation between the number of islets and the MPI signal (R 2 =0.988). Post-mortem MPI performed on day 1 after Tx showed high signal contrast in the liver and under the kidney capsule. Quantitation of the signal supports islet loss over time, which is normally observed 2 weeks after Tx. No MPI signal was observed in control animals. In vivo MRI confirmed the presence of labeled islets/islet clusters in liver parenchyma and under the kidney capsule one day after Tx.Conclusions: Here we demonstrate that MPI can be used for quantitative detection of labeled pancreatic islets in the liver and under the kidney capsule of experimental animals. We believe that MPI, a modality with no depth attenuation and zero background tissue signal could be a suitable method for imaging transplanted islet grafts.

Tolerogenic Iron Oxide Nanoparticles in Type 1 Diabetes: Biodistribution and Pharmacokinetics Studies in Nonobese Diabetic Mice

“…T1D development is invariably associated with changes in vascular permeability in pancreatic blood vessels . This increased microvascular permeability is observed already before high blood glucose diagnosis in prediabetic mice.…”

Current Progress and Perspective: Clinical Imaging of Islet Transplantation

“…Magnetic particle imaging (MPI) is an imaging method used to for detecting SPIO nanoparticles with advantages including: high specificity and sensitivity, the absence of the background signal, linear quantitative ability, and high potential for clinic translation. This new imaging technology has already been utilized for stem cell tracking [48,49] and islet transplantation [50], and other indications. MPI's great specificity results from its high image contrast, since magnetic particles serve as the only source for signal and are thus the only visualized element [51].…”

Superparamagnetic iron oxides as MPI tracers: A primer and review of early applications

“…The resulting “hot spot” MP and SPECT images are very similar in appearance and allow analysis of distribution in the lung, which is not possible with MRI using SPIO-labeled cells. Others have applied MPI cell tracking for visualization of SPIO-labeled islets engrafted in the liver and kidney capsule, where further cellular MPI quantification was demonstrated [24]. While Resovist and Feridex have similar T2 relaxivities and are approximately equally effective as MRI contrast agents, they have different performances in MPI as shown for both free particles and when internalized in cells [19].…”