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Quantification of B...
Quantification of Beta-Cell Mass in Intramuscular Islet Grafts using Radiolabeled Exendin-4
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- Espes, Daniel (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Institutionen för medicinska vetenskaper
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- Selvaraju, Ramkumar (författare)
- Uppsala universitet,Institutionen för läkemedelskemi
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- Velikyan, Irina (författare)
- Uppsala universitet,Institutionen för läkemedelskemi
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- Krajcovic, Martin (författare)
- Uppsala universitet,Institutionen för läkemedelskemi
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- Carlsson, Per-Ola (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Institutionen för medicinska vetenskaper
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- Eriksson, Olof (författare)
- Uppsala universitet,Institutionen för läkemedelskemi,Turku PET center, Faculty of Natural Sciences and Technology, Åbo Akademi, Turku, Finland
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(creator_code:org_t)
- 2016
- 2016
- Engelska.
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Ingår i: Transplantation Direct. - 2373-8731. ; 2:8
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: There is an increasing interest in alternative implantation sites to the liver for islet transplantation. Intramuscular implantation has even been tested clinically. Possibilities to monitor [beta]-cell mass would be of huge importance not only for the understanding of islet engraftment but also for the decision of changing the immunosuppressive regime. We have therefore evaluated the feasibility of quantifying intramuscular [beta]-cell mass using the radiolabeled glucagon like peptide-1 receptor agonist DO3A-VS-Cys40-Exendin-4.Methods: One hundred to 400 islets were transplanted to the abdominal muscle of nondiabetic mice. After 3 to 4 weeks, 0.2 to 0.5 MBq [177Lu]DO3A-VS-Cys40-Exendin-4 was administered intravenously. Sixty minutes postinjection abdominal organs and graft bearing muscle were retrieved, and the radioactive uptake measured in a well counter within 10 minutes. The specific uptake in native and transplanted islets was assessed by autoradiography. The total insulin-positive area of the islet grafts was determined by immunohistochemistry.Results: Intramuscular islet grafts could easily be visualized by this tracer, and the background uptake was very low. There was a linear correlation between the radioactivity uptake and the number of transplanted islets, both for standardized uptake values and the total radiotracer uptake in each graft (percentage of injected dose). The quantified total insulin area of surviving [beta] cells showed an even stronger correlation to both standardized uptake values (R = 0.96, P = 0.0002) and percentage of injected dose (R = 0.88, P = 0.0095). There was no correlation to estimated [alpha] cell mass.Conclusions: [177Lu]DO3A-VS-Cys40-Exendin-4 could be used to quantify [beta]-cell mass after experimental intramuscular islet transplantation. This technique may well be transferred to the clinical setting by exchanging Lutetium-177 radionuclide to a positron emitting Gallium-68.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Islet transplantation
- beta-cell mass
- exendin-4
- Lutetium-177
- Medical Cell Biology
- Medicinsk cellbiologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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