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01.05.2014 | Article

Non-invasive quantification of the beta cell mass by SPECT with ¹¹¹In-labelled exendin

verfasst von: Maarten Brom, Wietske Woliner-van der Weg, Lieke Joosten, Cathelijne Frielink, Thomas Bouckenooghe, Paul Rijken, Karolina Andralojc, Burkhard J. Göke, Marion de Jong, Decio L. Eizirik, Martin Béhé, Tony Lahoutte, Wim J. G. Oyen, Cees J. Tack, Marcel Janssen, Otto C. Boerman, Martin Gotthardt

Erschienen in: Diabetologia | Ausgabe 5/2014

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Abstract

Aims/hypothesis

A reliable method for in vivo quantification of pancreatic beta cell mass (BCM) could lead to further insight into the pathophysiology of diabetes. The glucagon-like peptide 1 receptor, abundantly expressed on beta cells, may be a suitable target for imaging. We investigated the potential of radiotracer imaging with the GLP-1 analogue exendin labelled with indium-111 for determination of BCM in vivo in a rodent model of beta cell loss and in patients with type 1 diabetes and healthy individuals.

Methods

The targeting of ¹¹¹In-labelled exendin was examined in a rat model of alloxan-induced beta cell loss. Rats were injected with 15 MBq ¹¹¹In-labelled exendin and single photon emission computed tomography (SPECT) acquisition was performed 1 h post injection, followed by dissection, biodistribution and ex vivo autoradiography studies of pancreatic sections. BCM was determined by morphometric analysis after staining with an anti-insulin antibody. For clinical evaluation SPECT was acquired 4, 24 and 48 h after injection of 150 MBq ¹¹¹In-labelled exendin in five patients with type 1 diabetes and five healthy individuals. The tracer uptake was determined by quantitative analysis of the SPECT images.

Results

In rats, ¹¹¹In-labelled exendin specifically targets the beta cells and pancreatic uptake is highly correlated with BCM. In humans, the pancreas was visible in SPECT images and the pancreatic uptake showed high interindividual variation with a substantially lower uptake in patients with type 1 diabetes.

Conclusions/interpretation

These studies indicate that ¹¹¹In-labelled exendin may be suitable for non-invasive quantification of BCM.

Trial registration ClinicalTrials.gov NCT01825148, EudraCT: 2012-000619-10

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Titel: Non-invasive quantification of the beta cell mass by SPECT with 111In-labelled exendin
verfasst von: Maarten Brom
Wietske Woliner-van der Weg
Lieke Joosten
Cathelijne Frielink
Thomas Bouckenooghe
Paul Rijken
Karolina Andralojc
Burkhard J. Göke
Marion de Jong
Decio L. Eizirik
Martin Béhé
Tony Lahoutte
Wim J. G. Oyen
Cees J. Tack
Marcel Janssen
Otto C. Boerman
Martin Gotthardt
Publikationsdatum: 01.05.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 5/2014
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-014-3166-3

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Aims/hypothesis

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