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Michelotti FC, Bowden G, Eter W, Küppers A, Maurer A, Nischwitz V, Pichler BJ, Gotthardt M, Schmid AM. Longitudinal multimodal monitoring of transplanted islet β-cells. Nucl Med Biol 2024; 138-139:108962. [PMID: 39393206 DOI: 10.1016/j.nucmedbio.2024.108962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 09/18/2024] [Accepted: 10/03/2024] [Indexed: 10/13/2024]
Abstract
PURPOSE Monitoring β-cell mass and function would provide a better understanding of diabetes, setting the stage for truly individualized therapies. We applied a combined PET/MRI protocol to monitor engrafted islets mass and function without pre-labeling of isolated cells. A PET tracer binding to GLP-1R quantifies β-cell mass, while Mn-CA characterizes β-cell function. Both parameters were assessed in transplanted and native β-cells in vivo and validated with autoradiography and mass spectrometry imaging. METHODS Islets were collected and transplanted into the calves of C3H-mice. Accumulation of [64Cu]Ex4 and Mn-CA was examined with a PET/MRI at 1 h post-injection between 1 and 4 weeks after the transplantation. A separate blocking study with diazoxide targeted the functionality of the transplanted islets. As validation, ex vivo autoradiography and LA-ICP-MS imaging were performed after the last imaging session. RESULTS PET/MRI monitored the engraftment of transplanted islets and visualized an increasing uptake of the PET tracer and Mn-CA. The Mn-CA accumulated at a higher islet-to-background ratio in the calf of mice than in the pancreas due to the high retention of Mn-CA in the exocrine pancreas. In vivo imaging data correlated well with autoradiography and LA-ICP-MS imaging, validating the in vivo approaches. CONCLUSION For the quantification of β-cell function, Mn-based contrast mechanisms between native and transplanted islets differ and require further studies for optimal biological readout. However, non-invasive PET/MRI nonetheless provides the tools to investigate the relationship between β-cell mass and function in pancreatic islets.
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Affiliation(s)
- Filippo C Michelotti
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
| | - Gregory Bowden
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
| | - Wael Eter
- Radboud University Nijmegen Medical Centre, Department of Radiology Nuclear Medicine, Nijmegen, the Netherlands.
| | - Astrid Küppers
- Forschungszentrum Jülich GmbH, Central Institute of Engineering, Electronics and Analytics, Jülich, Germany.
| | - Andreas Maurer
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
| | - Volker Nischwitz
- Forschungszentrum Jülich GmbH, Central Institute of Engineering, Electronics and Analytics, Jülich, Germany.
| | - Bernd J Pichler
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
| | - Martin Gotthardt
- Radboud University Nijmegen Medical Centre, Department of Radiology Nuclear Medicine, Nijmegen, the Netherlands.
| | - Andreas M Schmid
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
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Purich K, Cai H, Yang B, Xu Z, Tessier AG, Black A, Hung RW, Boivin E, Xu B, Wu P, Zhang B, Xin D, Fallone BG, Rajotte RV, Wu Y, Rayat GR. MRI monitoring of transplanted neonatal porcine islets labeled with polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles in a mouse model. Xenotransplantation 2021; 29:e12720. [PMID: 34850455 DOI: 10.1111/xen.12720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 09/25/2021] [Accepted: 10/22/2021] [Indexed: 11/27/2022]
Abstract
Islet transplantation is a potential treatment option for certain patients with type 1 diabetes; however, it still faces barriers to widespread use, including the lack of tools to monitor islet grafts post-transplantation. This study investigates whether labeling neonatal porcine islets (NPI) with polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) affects their function, and whether this nanoparticle can be utilized to monitor NPI xenografts with magnetic resonance imaging (MRI) in a mouse model. In vitro, PVP-SPIO-labeled NPI in an agarose gel was visualized clearly by MRI. PVP-SPIO-labeled islets were then transplanted under the kidney capsules of immunodeficient nondiabetic and diabetic mice. All diabetic mice that received transplantation of PVP-SPIO-labeled islets reached normoglycemia. Grafts appeared as hypo-intense areas on MRI and were distinguishable from the surrounding tissues. Following injection of spleen cells from immunocompetent mice, normoglycemic recipient mice became diabetic and islet grafts showed an increase in volume, accompanied by a mixed signal on MRI. Overall, this study demonstrates that PVP-SPIO did not affect the function of NPI that PVP-SPIO-labeled islets were easily seen on MRI, and changes in MRI signals following rejection suggest a potential use of PVP-SPIO-labeled islets to monitor graft viability.
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Affiliation(s)
- Kieran Purich
- Department of Surgery, Ray Rajotte Surgical-Medical Research Institute, Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Haolei Cai
- Department of Surgery, 2nd Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, China
| | - Bin Yang
- Department of Surgery, 2nd Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, China
| | - Zhihao Xu
- Department of Surgery, Ray Rajotte Surgical-Medical Research Institute, Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Anthony G Tessier
- Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.,Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Adnan Black
- Department of Surgery, Ray Rajotte Surgical-Medical Research Institute, Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Ryan W Hung
- Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Alberta, Canada
| | - Eric Boivin
- Department of Surgery, Ray Rajotte Surgical-Medical Research Institute, Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Baoyou Xu
- Department of Surgery, Ray Rajotte Surgical-Medical Research Institute, Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Ping Wu
- Department of Surgery, Ray Rajotte Surgical-Medical Research Institute, Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Bo Zhang
- Department of Surgery, 2nd Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, China
| | - Dong Xin
- Department of Surgery, 2nd Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, China
| | - Biagio Gino Fallone
- Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.,Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Ray V Rajotte
- Department of Surgery, Ray Rajotte Surgical-Medical Research Institute, Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Yulian Wu
- Department of Surgery, 2nd Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, China
| | - Gina R Rayat
- Department of Surgery, Ray Rajotte Surgical-Medical Research Institute, Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
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Zheng L, Wang Y, Yang B, Zhang B, Wu Y. Islet Transplantation Imaging in vivo. Diabetes Metab Syndr Obes 2020; 13:3301-3311. [PMID: 33061492 PMCID: PMC7520574 DOI: 10.2147/dmso.s263253] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Accepted: 07/29/2020] [Indexed: 12/31/2022] Open
Abstract
Although islet transplantation plays an effective and powerful role in the treatment of diabetes, a large amount of islet grafts are lost at an early stage due to instant blood-mediated inflammatory reactions, immune rejection, and β-cell toxicity resulting from immunosuppressive agents. Timely intervention based on the viability and function of the transplanted islets at an early stage is crucial. Various islet transplantation imaging techniques are available for monitoring the conditions of post-transplanted islets. Due to the development of various imaging modalities and the continuous study of contrast agents, non-invasive islet transplantation imaging in vivo has made great progress. The tracing and functional evaluation of transplanted islets in vivo have thus become possible. However, most studies on contrast agent and imaging modalities are limited to animal experiments, and long-term toxicity and stability need further evaluation. Accordingly, the clinical application of the current achievements still requires a large amount of effort. In this review, we discuss the contrast agents for MRI, SPECT/PET, BLI/FI, US, MPI, PAI, and multimodal imaging. We further summarize the advantages and limitations of various molecular imaging methods.
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Affiliation(s)
- Lei Zheng
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310000, People’s Republic of China
| | - Yinghao Wang
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310000, People’s Republic of China
| | - Bin Yang
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310000, People’s Republic of China
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310000, People’s Republic of China
| | - Bo Zhang
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310000, People’s Republic of China
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310000, People’s Republic of China
- Correspondence: Bo Zhang; Yulian Wu Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310000, People’s Republic of China Tel/Fax +86 571 87783563 Email ;
| | - Yulian Wu
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310000, People’s Republic of China
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310000, People’s Republic of China
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Barsanti C, Lenzarini F, Kusmic C. Diagnostic and prognostic utility of non-invasive imaging in diabetes management. World J Diabetes 2015; 6:792-806. [PMID: 26131322 PMCID: PMC4478576 DOI: 10.4239/wjd.v6.i6.792] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Revised: 12/23/2014] [Accepted: 04/14/2015] [Indexed: 02/05/2023] Open
Abstract
Medical imaging technologies are acquiring an increasing relevance to assist clinicians in diagnosis and to guide management and therapeutic treatment of patients, thanks to their non invasive and high resolution properties. Computed tomography, magnetic resonance imaging, and ultrasonography are the most used imaging modalities to provide detailed morphological reconstructions of tissues and organs. In addition, the use of contrast dyes or radionuclide-labeled tracers permits to get functional and quantitative information about tissue physiology and metabolism in normal and disease state. In recent years, the development of multimodal and hydrid imaging techniques is coming to be the new frontier of medical imaging for the possibility to overcome limitations of single modalities and to obtain physiological and pathophysiological measurements within an accurate anatomical framework. Moreover, the employment of molecular probes, such as ligands or antibodies, allows a selective in vivo targeting of biomolecules involved in specific cellular processes, so expanding the potentialities of imaging techniques for clinical and research applications. This review is aimed to give a survey of characteristics of main diagnostic non-invasive imaging techniques. Current clinical appliances and future perspectives of imaging in the diagnostic and prognostic assessment of diabetic complications affecting different organ systems will be particularly addressed.
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