Non-invasive in vivo determination of viable islet graft volume by 111In-exendin-3

Abstract Pancreatic islet transplantation is a promising therapy for patients with type 1 diabetes. However, the duration of long-term graft survival is limited due to inflammatory as well as non-inflammatory processes and routine clinical tests are not suitable to monitor islet survival. 111In-exen...

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Main Authors: Wael A. Eter, Inge Van der Kroon, Karolina Andralojc, Mijke Buitinga, Stefanie M. A. Willekens, Cathelijne Frielink, Desiree Bos, Lieke Joosten, Otto C. Boerman, Maarten Brom, Martin Gotthardt
Format: Article
Language:English
Published: Nature Publishing Group 2017-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-07815-3
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spelling doaj-54496705e6054b69a78f30ff906bdda12020-12-08T02:06:45ZengNature Publishing GroupScientific Reports2045-23222017-08-01711610.1038/s41598-017-07815-3Non-invasive in vivo determination of viable islet graft volume by 111In-exendin-3Wael A. Eter0Inge Van der Kroon1Karolina Andralojc2Mijke Buitinga3Stefanie M. A. Willekens4Cathelijne Frielink5Desiree Bos6Lieke Joosten7Otto C. Boerman8Maarten Brom9Martin Gotthardt10Department of Radiology and Nuclear Medicine, Radboud University Medical CentreDepartment of Radiology and Nuclear Medicine, Radboud University Medical CentreDepartment of Radiology and Nuclear Medicine, Radboud University Medical CentreDepartment of Radiology and Nuclear Medicine, Radboud University Medical CentreDepartment of Radiology and Nuclear Medicine, Radboud University Medical CentreDepartment of Radiology and Nuclear Medicine, Radboud University Medical CentreDepartment of Radiology and Nuclear Medicine, Radboud University Medical CentreDepartment of Radiology and Nuclear Medicine, Radboud University Medical CentreDepartment of Radiology and Nuclear Medicine, Radboud University Medical CentreDepartment of Radiology and Nuclear Medicine, Radboud University Medical CentreDepartment of Radiology and Nuclear Medicine, Radboud University Medical CentreAbstract Pancreatic islet transplantation is a promising therapy for patients with type 1 diabetes. However, the duration of long-term graft survival is limited due to inflammatory as well as non-inflammatory processes and routine clinical tests are not suitable to monitor islet survival. 111In-exendin-SPECT (single photon emission computed tomography) is a promising method to non-invasively image islets after transplantation and has the potential to help improve the clinical outcome. Whether 111In-exendin-SPECT allows detecting small differences in beta-cell mass (BCM) and measuring the actual volume of islets that were successfully engrafted has yet to be demonstrated. Here, we evaluated the performance of 111In-exendin-SPECT using an intramuscular islet transplantation model in C3H mice. In vivo imaging of animals transplanted with 50, 100, 200, 400 and 800 islets revealed an excellent linear correlation between SPECT quantification of 111In-exendin uptake and insulin-positive area of islet transplants, demonstrating that 111In-exendin-SPECT specifically and accurately measures BCM. The high sensitivity of the method allowed measuring small differences in graft volumes, including grafts that contained less than 50 islets. The presented method is reliable, convenient and holds great potential for non-invasive monitoring of BCM after islet transplantation in humans.https://doi.org/10.1038/s41598-017-07815-3
collection DOAJ
language English
format Article
sources DOAJ
author Wael A. Eter
Inge Van der Kroon
Karolina Andralojc
Mijke Buitinga
Stefanie M. A. Willekens
Cathelijne Frielink
Desiree Bos
Lieke Joosten
Otto C. Boerman
Maarten Brom
Martin Gotthardt
spellingShingle Wael A. Eter
Inge Van der Kroon
Karolina Andralojc
Mijke Buitinga
Stefanie M. A. Willekens
Cathelijne Frielink
Desiree Bos
Lieke Joosten
Otto C. Boerman
Maarten Brom
Martin Gotthardt
Non-invasive in vivo determination of viable islet graft volume by 111In-exendin-3
Scientific Reports
author_facet Wael A. Eter
Inge Van der Kroon
Karolina Andralojc
Mijke Buitinga
Stefanie M. A. Willekens
Cathelijne Frielink
Desiree Bos
Lieke Joosten
Otto C. Boerman
Maarten Brom
Martin Gotthardt
author_sort Wael A. Eter
title Non-invasive in vivo determination of viable islet graft volume by 111In-exendin-3
title_short Non-invasive in vivo determination of viable islet graft volume by 111In-exendin-3
title_full Non-invasive in vivo determination of viable islet graft volume by 111In-exendin-3
title_fullStr Non-invasive in vivo determination of viable islet graft volume by 111In-exendin-3
title_full_unstemmed Non-invasive in vivo determination of viable islet graft volume by 111In-exendin-3
title_sort non-invasive in vivo determination of viable islet graft volume by 111in-exendin-3
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2017-08-01
description Abstract Pancreatic islet transplantation is a promising therapy for patients with type 1 diabetes. However, the duration of long-term graft survival is limited due to inflammatory as well as non-inflammatory processes and routine clinical tests are not suitable to monitor islet survival. 111In-exendin-SPECT (single photon emission computed tomography) is a promising method to non-invasively image islets after transplantation and has the potential to help improve the clinical outcome. Whether 111In-exendin-SPECT allows detecting small differences in beta-cell mass (BCM) and measuring the actual volume of islets that were successfully engrafted has yet to be demonstrated. Here, we evaluated the performance of 111In-exendin-SPECT using an intramuscular islet transplantation model in C3H mice. In vivo imaging of animals transplanted with 50, 100, 200, 400 and 800 islets revealed an excellent linear correlation between SPECT quantification of 111In-exendin uptake and insulin-positive area of islet transplants, demonstrating that 111In-exendin-SPECT specifically and accurately measures BCM. The high sensitivity of the method allowed measuring small differences in graft volumes, including grafts that contained less than 50 islets. The presented method is reliable, convenient and holds great potential for non-invasive monitoring of BCM after islet transplantation in humans.
url https://doi.org/10.1038/s41598-017-07815-3
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