Preliminary study on the dynamic positron emission tomography imaging with 11C-ER176 to delineate macrophage activation in diabetic gastroparesis

Neurogastroenterol Motil. 2024 May;36(5):e14762. doi: 10.1111/nmo.14762. Epub 2024 Feb 20.

Abstract

Background: Animal models and human data have suggested macrophage-driven immune dysregulation in diabetic gastroparesis (DG). Translocator protein (TSPO) upregulation has been suggested to indicate activated state of macrophages and ER176 is a high affinity third generation TSPO-specific radioligand. The aim of this study was to determine feasibility of dynamic 11C-ER 176 PET to identify macrophage activation in DG.

Methods: Twelve patients, all females, were recruited (4 DG, 4 diabetics, and 4 healthy volunteers) for 11C-ER 176 PET/CT scanning. The standardized uptake value (SUVmax) in the gastric fundus, body, pylorus, and descending part of the duodenum were compared between three groups using Kruskal-Wallis test to perform the comparisons, and a p-value of 0.05 was considered statistically significant.

Key results: Age was comparable among the three groups with a median of 53 years. The uptake was higher in pylorus in diabetics compared to DG and healthy (SUVmax healthy 4.6 ± 0.2, diabetics 8.4 ± 4.1, DG 5.5 ± 1.0, p = 0.04). The uptake was similar in gastric fundus (9.0 ± 1.6, 13.1 ± 8.3, 7.8 ± 1.9 respectively, p = 0.3), body (7.7 ± 1.9, 13 ± 9.2, 7.8 ± 1.9 respectively, p = 0.8), and duodenum (6.2 ± 2.1, 9.5 ± 6.8, 7.0 ± 1.8 respectively, p = 0.6). No correlation was observed between SUVmax uptake and either HbA1C or fasting blood glucose.

Conclusions and inferences: Female diabetic gastroparesis patients did not demonstrate increased TSPO ligand 11C-ER 176 uptake in the stomach. Possible explanations include lack of specificity of ligand for specific macrophage phenotypes in DG, sex effect, or small sample size. Further studies investigating non-invasive ways of analyzing immune dysregulation in neurogastrointestinal disorders are warranted.

Keywords: TSPO protein; diabetes mellitus; gastroparesis; macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carbon Radioisotopes
  • Diabetes Complications / diagnostic imaging
  • Female
  • Gastroparesis* / diagnostic imaging
  • Humans
  • Macrophage Activation*
  • Middle Aged
  • Positron Emission Tomography Computed Tomography / methods
  • Positron-Emission Tomography / methods

Substances

  • Carbon Radioisotopes