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Positron emission tomography in clinical islet transplantation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology. (Korsgren)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
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2009 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 9, no 12, 2816-2824 p.Article in journal (Refereed) Published
Abstract [en]

The fate of islets in clinical transplantation is unclear. To elude on this positron emission tomography combined with computed tomography (PET/CT) was performed for 60 min during islet transplantation in five patients receiving six transplants. A fraction of the islets (23%) were labeled with 18F-fluorodeoxyglucose ([(18)F]FDG) and carefully mixed with unlabeled islets just prior to intraportal transplantation. The peak radioactivity concentration in the liver was found at 19 min after start of islet infusion and corresponded to only 75% of what was expected, indicating that islets are lost during the transplantation procedure. No accumulation of radioactivity was found in the lungs. A nonphysiological peak of C-peptide was found in plasma during and immediately after transplantation in all subjects. Distribution in the liver was heterogeneous with wide variations in location and concentration. Islets found in areas with concentrations of >400 IEQ/cc liver tissue varied between 1% and 32% of the graft in different subjects. No side effects attributed to the PET/CT procedure were found. Clinical outcome in all patients was comparable to that previously observed indicating that the [(18)F]FDG labeling procedure did not harm the islets. The technique has potential to be used to assess approaches to enhance islet survival and engraftment in clinical transplantation.

Place, publisher, year, edition, pages
2009. Vol. 9, no 12, 2816-2824 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-111860DOI: 10.1111/j.1600-6143.2009.02844.xISI: 000272127600023PubMedID: 19845588OAI: oai:DiVA.org:uu-111860DiVA: diva2:283494
Available from: 2009-12-28 Created: 2009-12-28 Last updated: 2015-06-15Bibliographically approved
In thesis
1. Imaging Islets of Langerhans by Positron Emission Tomography: Quantification of Beta-Cell Mass in the Native Pancreas and the Islet Graft
Open this publication in new window or tab >>Imaging Islets of Langerhans by Positron Emission Tomography: Quantification of Beta-Cell Mass in the Native Pancreas and the Islet Graft
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Type 1 and 2 Diabetes Mellitus are a growing health problem throughout the world. There is an increasing  need for methodologies, which are both reliable and non-invasive to measure the amount of insulin-producing tissue (Beta-cell mass, or BCM), as well as rapidly quantify changes in the BCM due to the onset of disease, beta-cell replacement therapy, or other treatments.

Positron Emission Tomography (PET) is a non-invasive, quantitative functional imaging technique which can be used to study dynamical or static processes inside the body.

In this thesis, we present a study protocol for in vivo imaging of the most common form of beta- cell replacement therapy; islet transplantation. Islets were labeled with the PET tracer, 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG), and administered intra-portally, while the recipient was monitored by PET/CT. The hepatic distribution of the islets was highly heterogeneous, and around 25% (human) or 50% (porcine) of the administered islets could not be found in the liver after completed transplantation, confirming previous reports of considerable cell injury during the procedure leading to low hepatic engraftment.

Native BCM in the pancreas can potentially be quantified using a PET tracer with sufficiently high specificity, but the major obstacle is the relative low amounts of insulin producing tissue (only 1-2% of the pancreatic volume). Two tetrabenazine analogues, [18F]FE-(+)-DTBZ and [18F]FE-(+)-DTBZ-d4, are ligands to VMAT2, which is expressed in islet tissue. Both analogues were investigated and characterized as potential BCM imaging agents both in vitro and in vivo.  Both tracers exhibited high preferential binding to islet tissue compared to exocrine pancreatic tissue. However, the specificity was not high enough to overcome the obscuring exocrine signal in vivo (7-10% of the signal originating from specific islet tracer uptake).

This thesis demonstrates that it is possible to quantitatively assess islet transplantation by PET imaging. In vivo determination of native pancreatic BCM is, in theory, possible with both [18F]FE-(+)-DTBZ and [18F]FE-(+)-DTBZ-d4, but tracer analogues with higher islet specificity is needed for quantification of smaller BCM changes with physiological impact.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 67 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 635
Keyword
Positron Emission Tomography, [18F]FDG, dihydrotetrabenazine, Islet transplantation, IBMIR, beta-cell mass
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-136372 (URN)978-91-554-7978-7 (ISBN)
Public defence
2011-02-04, Rosénsalen, Akademiska Sjukhuset, Ingång 95/96, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2011-01-14 Created: 2010-12-12 Last updated: 2011-03-11

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Eriksson, OlofSundin, AndersTufveson, Gunnar

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