Non-invasive quantification of the beta cell mass by SPECT with ¹¹¹In-labelled exendin.
OBJECTIVE
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 (111)In-labelled exendin was examined in a rat model of alloxan-induced beta cell loss. Rats were injected with 15 MBq (111)In-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 (111)In-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, (111)In-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
These studies indicate that (111)In-labelled exendin may be suitable for non-invasive quantification of BCM.


BACKGROUND
ClinicalTrials.gov NCT01825148, EudraCT: 2012-000619-10.
Department of Radiology and Nuclear Medicine, Radboud university medical center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands, maarten.brom@radboudumc.nl.
Maarten
M
Brom
Wietske
W
Woliner-van der Weg
Lieke
L
Joosten
Cathelijne
C
Frielink
Thomas
T
Bouckenooghe
Paul
P
Rijken
Karolina
K
Andralojc
Burkhard J
BJ
Göke
Marion
M
de Jong
Decio L
DL
Eizirik
Martin
M
Béhé
Tony
T
Lahoutte
Wim J G
WJ
Oyen
Cees J
CJ
Tack
Marcel
M
Janssen
Otto C
OC
Boerman
Martin
M
Gotthardt
D000293:Adolescent; D000328:Adult; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000000981:diagnostic imaging*; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007205:Indium Radioisotopes; D050417:Insulin-Secreting Cells / Q000000981:diagnostic imaging*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D010455:Peptides; D019275:Radiopharmaceuticals; D051381:Rats; D018027:Receptors, Glucagon / Q000378:metabolism; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D055815:Young Adult
C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007205:Indium Radioisotopes; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D019275:Radiopharmaceuticals; D018027:Receptors, Glucagon; C043046:helospectin I