Positron Emission Tomography: A Real-Time Tool to Quantify Early Islet Engraftment in a Preclinical Large Animal Model
Abstract
Background Clinical islet transplantation is currently being explored as a therapeutic option for persons with type I diabetes and hypoglycemic unawareness. Techniques to monitor graft survival are urgently needed to optimize the procedure. Therefore, the objective of the present study was to develop a technique for imaging survival of transplanted islets in the peritransplant and early posttransplant phase. Methods Isolated porcine islets were labeled in vitro with 2-deoxy-2[F]fluoro-D-glucose ([F]FDG) and infused intraportally into anesthetized pigs (n=10). Dynamic examination was performed on a positron emission tomography/computed tomography hybrid system. Results More than 95% of the radioactivity was confined to the islets at the time of transplantation. The peak percentage of infused radioactivity within the liver, quantified at the end of the islet infusion, was only 54+/-5.1%. The distribution of the radioactivity in the liver was found to be heterogeneous. A whole-body examination showed no accumulation in the lungs or brain; extrahepatic radioactivity was, except urinary excretion, evenly distributed in the pig body. Conclusions Our results imply that almost 50% of the islets were damaged to the extent that the FDG contained was release within minutes after intraportal transplantation. The distribution of radioactivity without accumulation in the brain indicates that the activity is released from lysed islet cells in the form of [F]FDG-6P rather than native [F]FDG.…
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Early investigation of primary human islet transplants and animal studies demonstrated that 50% or more of the islet graft was lost during the first few days after transplantation.
“Early investigation of primary human islet transplants56 and animal studies122,123 demonstrated that 50% or more of the islet graft was lost during the first few days after transplantation.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [122]
Cites
Sokoloff, L., Reivich, M., Kennedy, C., Rosiers, M. H. D., Patlak, C. S., Pettigrew, K. D., Sakurada, O., & Shinohara, M. (1977) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1977.tb10649.x · Cited by 6,000 · see citing works
Moberg, L., Johansson, H., Lukinius, A., Berne, C., Foss, A., Källen, R., Østraat, Ø., Salmela, K., Tibell, A., Tufveson, G., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)12020-4 · Cited by 568 · see citing works
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Update on Islet Transplantation
McCall, M., & James Shapiro, A. M. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a007823 · Cited by 226 · see citing works
Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes
Hogrebe, N. J., Ishahak, M., & Millman, J. R. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.04.002 · Cited by 210 · see citing works
- Authors
- Eich, T., Eriksson, O., Sundin, A., Estrada, S., Brandhorst, D., Brandhorst, H., Langstrom, B., Nilsson, B., Korsgren, O., & Lundgren, T.
- Affiliations
- Uppsala University Hospital (SE)
- ORCID
- Venue
- Transplantation
- Published
- 2007-10-15
- Volume
- 84
- Issue
- 7
- Pages
- 893-898
- ISSN
- 0041-1337 (ISSN-L)
- OpenAlex
- W2011554814
- Cited by
- 106
- References
- 2
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 11 · 2012: 7
- FWCI
- 8.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Transplantation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Keywords
- islet transplantation, islet engraftment, positron emission tomography, FDG-PET, porcine islets, type 1 diabetes, hypoglycemia unawareness, pigs
- MeSH terms
- Animals, Autoradiography, Diagnostic Imaging, Disease Models, Animal, Glucose, Graft Survival, Islets of Langerhans, Swine, Time Factors, Tomography, X-Ray Computed, Islets of Langerhans Transplantation, Positron-Emission Tomography
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