Acetylcholinesterase-associated inflammation in patients with giant cell arteritis. Evaluation by histology and 11C-donepezil PET/CT

• Published in: Clinical and experimental rheumatology 2019-03, Vol.37 Suppl 117 (2), p.20-25
• Main Authors: Therkildsen, Philip, Nielsen, Berit Dalsgaard, Hansen, Ib Tønder, Keller, Kresten Krarup, Steiniche, Torben, Gormsen, Lars Christian, Borghammer, Per, Hauge, Ellen-Margrethe
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase - metabolism; Carbon Radioisotopes; Donepezil; Fluorodeoxyglucose F18; Giant Cell Arteritis - diagnostic imaging; Giant Cell Arteritis - enzymology; Giant Cell Arteritis - pathology; Humans; Inflammation; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals
• ISSN: 0392-856X

To investigate the in-situ expression of acetylcholinesterase (AChE) in the inflamed vessel wall of patients with biopsy-positive giant cell arteritis (GCA) as compared to biopsy-negative non-GCA patients, and to evaluate the in-vivo expression of AChE in patients with large-vessel GCA (LVGCA) by 11C-donepezil (AChE inhibitor) positron emission tomography/computed tomography (PET/CT). Twenty-four biopsy-positive GCA and 44 biopsy-negative non-GCA patients were included for AChE histology. Immunohistochemical methods were used to determine the AChE expression. The histological inflammation and the AChE expression were assessed by an experienced pathologist on a 3-point scale. Two patients with newly diagnosed 18F-fluorodeoxyglucose (18F-FDG) PET/CT verified LVGCA were included for 11C-donepezil PET/CT. PET images were assessed by an experienced nuclear medicine physician. AChE was expressed in all 24 positive temporal artery biopsies, 10/24 showed high AChE expression (grade 2) and 14/24 showed moderate AChE expression (grade 1). No AChE expression was observed outside the media smooth muscle cells (grade 0) in any of the biopsy-negative non-GCA patients. The AChE expression was in 86% agreement with the histological inflammation. The AChE expression was not associated with any clinical or biochemical findings. In both LV-GCA patients, PET/CT revealed extensive vascular FDG uptake but no 11C-donepezil uptake. AChE is highly expressed in the inflamed vessel wall of patients with GCA. Although, 11C-donepezil PET/CT showed no vascular uptake in the FDG PET/CT verified LV-GCA patients, histological findings raise the possibility that AChE can be used in the development of new diagnostic and disease monitoring tools for GCA.