< Terug naar vorige pagina

Publicatie

Measuring the Pancreatic β Cell Mass in Vivo with Exendin SPECT during Hyperglycemia and Severe Insulitis

Tijdschriftbijdrage - Tijdschriftartikel

OBJECTIVE: Targeting the glucagon-like peptide-1 receptor with radiolabeled exendin is a very promising method to noninvasively determine the β cell mass in the pancreas, which is needed to unravel the pathophysiology of type 1 and type 2 diabetes. The present study aimed to explore the effects of both hyperglycemia and insulitis on the uptake of exendin in a spontaneous type 1 diabetes mouse model, nonobese diabetic (NOD) mice.

METHODS: NOD mice (n = 75, 7-21 weeks old) were injected intravenously with [111In]In-DTPA-exendin-3, and single-photon emission computed tomography (SPECT) images were acquired 1 h pi. The pancreatic accumulation of [111In]In-DTPA-exendin-3 was quantified in vivo using SPECT and by ex vivo counting and correlated to the β cell mass (BCM). The influence of insulitis and hyperglycemia on the exendin uptake was assessed.

RESULTS: The pancreas could be visualized longitudinally using SPECT. A linear correlation was found between the BCM (%) and pancreatic uptake (%ID/g) as measured by ex vivo counting (Pearson r = 0.64, p < 0.001), which was not affected by either insulitis (Pearson r = 0.66, p = 0.83) or hyperglycemia (Pearson r = 0.57, p = 0.51). Biodistribution and ex vivo autoradiography revealed remaining [111In]In-DTPA-exendin-3 uptake in the pancreas despite total ablation of BCM.

CONCLUSIONS: Despite hyperglycemia and severe insulitis, we have found a good correlation between BCM and pancreatic exendin uptake, even in a suboptimal model with relatively high background activity.

Tijdschrift: Molecular Pharmaceutics
ISSN: 1543-8384
Issue: 9
Volume: 16
Pagina's: 4024-4030
Jaar van publicatie:2019
Trefwoorden:GLP-1R, NOD mice, SPECT, exendin, receptor imaging, β cell mass
CSS-citation score:2
Toegankelijkheid:Closed