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Visualization of early engraftment in clinical islet transplantation by positron-emission tomography
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
2007 (Engelska)Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 356, nr 26, s. 2754-2755Artikel i tidskrift, Letter (Refereegranskat) Published
Ort, förlag, år, upplaga, sidor
2007. Vol. 356, nr 26, s. 2754-2755
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-103621ISI: 000247564500035PubMedID: 17596618OAI: oai:DiVA.org:uu-103621DiVA, id: diva2:218631
Tillgänglig från: 2009-05-20 Skapad: 2009-05-20 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
Ingår i avhandling
1. Imaging Islets of Langerhans by Positron Emission Tomography: Quantification of Beta-Cell Mass in the Native Pancreas and the Islet Graft
Öppna denna publikation i ny flik eller fönster >>Imaging Islets of Langerhans by Positron Emission Tomography: Quantification of Beta-Cell Mass in the Native Pancreas and the Islet Graft
2011 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2011. s. 67
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 635
Nyckelord
Positron Emission Tomography, [18F]FDG, dihydrotetrabenazine, Islet transplantation, IBMIR, beta-cell mass
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:uu:diva-136372 (URN)978-91-554-7978-7 (ISBN)
Disputation
2011-02-04, Rosénsalen, Akademiska Sjukhuset, Ingång 95/96, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2011-01-14 Skapad: 2010-12-12 Senast uppdaterad: 2011-03-11

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PubMedhttp://www.nejm.org/doi/full/10.1056/NEJMc070201

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Eriksson, Olof

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