Comparison of 68Ga-DOTA-Siglec-9 and 18F-Fluorodeoxyribose-Siglec-9: Inflammation Imaging and Radiation Dosimetry.

Helena Virtanen,Kerttuli Helariutta,Riikka Siitonen,Juhani Knuuti,Sirpa Jalkanen,Meeri Käkelä,Sanna Hellberg,Tuula Tolvanen,Xiang-Guo Li,Anne Roivainen,Johanna M U Silvola,Anu J Airaksinen,Mia Ståhle,Antti Saraste,Heidi Liljenbäck,Tibor Z Veres,Anu Autio

doi:10.1155/2017/7645070

Abstract

Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a ligand of inflammation-inducible vascular adhesion protein-1 (VAP-1). We compared 68Ga-DOTA- and 18F-fluorodeoxyribose- (FDR-) labeled Siglec-9 motif peptides for PET imaging of inflammation. Methods. Firstly, we examined 68Ga-DOTA-Siglec-9 and 18F-FDR-Siglec-9 in rats with skin/muscle inflammation. We then studied 18F-FDR-Siglec-9 for the detection of inflamed atherosclerotic plaques in mice and compared it with previous 68Ga-DOTA-Siglec-9 results. Lastly, we estimated human radiation dosimetry from the rat data. Results. In rats, 68Ga-DOTA-Siglec-9 (SUV, 0.88 ± 0.087) and 18F-FDR-Siglec-9 (SUV, 0.77 ± 0.22) showed comparable (P = 0.29) imaging of inflammation. In atherosclerotic mice, 18F-FDR-Siglec-9 detected inflamed plaques with a target-to-background ratio (1.6 ± 0.078) similar to previously tested 68Ga-DOTA-Siglec-9 (P = 0.35). Human effective dose estimates for 68Ga-DOTA-Siglec-9 and 18F-FDR-Siglec-9 were 0.024 and 0.022 mSv/MBq, respectively. Conclusion. Both tracers are suitable for PET imaging of inflammation. The easier production and lower cost of 68Ga-DOTA-Siglec-9 present advantages over 18F-FDR-Siglec-9, indicating it as a primary choice for clinical studies.

Highlights

Inflammation plays role in several diseases, such as, rheumatoid arthritis, diabetes and atherosclerosis
The early detection of inflammatory foci is critical for the adequate treatment of patients, and quantitative PET imaging may provide a valuable tool for diagnosis and monitoring of the effects of therapeutic interventions. 18F-FDG is the gold standard for PET, but not specific to inflammation
Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule, which is involved in leukocyte transendothelial migration from blood into the sites of inflammation

Summary

Introduction

Inflammation plays role in several diseases, such as, rheumatoid arthritis, diabetes and atherosclerosis. The early detection of inflammatory foci is critical for the adequate treatment of patients, and quantitative PET imaging may provide a valuable tool for diagnosis and monitoring of the effects of therapeutic interventions. 18F-FDG is the gold standard for PET, but not specific to inflammation. The high physiological accumulation of 18F-FDG in heart and brain makes it difficult to detect inflammatory foci close to these organs [1]. Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule, which is involved in leukocyte transendothelial migration from blood into the sites of inflammation. During inflammation VAP-1 translocates from intracellular storages on the endothelial cell surface where it contributes leukocyte-endothelial adhesion. VAP1 plays important role in early phases of inflammation, its luminal expression on the endothelium will remain constant

Methods

Results

Conclusion