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Cartilage. 2018 Apr;9(2):183-191. doi: 10.1177/1947603517738073. Epub 2017 Nov 3.

Imaging of Folate Receptor Expressing Macrophages in the Rat Groove Model of Osteoarthritis: Using a New DOTA-Folate Conjugate.

Author information

1
1 Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
2
2 Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.
3
3 Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
4
4 Centre for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
5
5 MILabs B.V., Utrecht, The Netherlands.
6
6 Section of Radiation, Detection & Medical Imaging, Applied Sciences, Delft University of Technology, Delft, The Netherlands.
7
7 Department for Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
8
8 Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
9
9 Department of Biomechanical Engineering, Delft University of Technology, Delft, The Netherlands.

Abstract

Objective To evaluate the presence and localization of folate receptor expressing macrophages in the rat groove model of osteoarthritis and determine the suitability of a new folate conjugate with albumin-binding entity (cm09) for in vivo SPECT (single-photon emission computed tomography) analysis. Design In male Wistar rats, local cartilage damage was induced in addition to a standard ( n = 10) or high-fat diet ( n = 6). After 12 weeks, 111In labeled folate conjugates were administered, and SPECT/CT (computed tomography) imaging was performed after 24 hours. Subsequently, osteoarthritis severity and folate receptor expression were assessed using (immuno)-histological sections. Results In vivo SPECT/CT imaging of the new folate conjugate (cm09) was as useful as a folate conjugate without albumin-binding entity in the groove model of osteoarthritis with less renal accumulation. Induction of cartilage damage on a standard diet resulted in no effect on the amount of folate receptor expressing macrophages compared with the contralateral sham operated joints. In contrast, inducing cartilage damage in the high-fat diet group resulted in 28.4% increase of folate receptor expression as compared with the nondamaged control joints. Folate receptor expressing cells were predominantly present in the synovial lining and in subchondral bone as confirmed by immunohistochemistry. Conclusions Folate receptor expression, and thus macrophage activation, can clearly be demonstrated in vivo, in small animal models of osteoarthritis using the new 111In-folate conjugate with specific binding to the folate receptor. Increased macrophage activity only plays a role in the groove model of osteoarthritis when applied in a high-fat diet induced dysmetabolic condition, which is in line with the higher inflammatory state of that specific model.

KEYWORDS:

animal model; imaging; inflammation; macrophages; osteoarthritis

PMID:
29096521
PMCID:
PMC5871123
DOI:
10.1177/1947603517738073
[Indexed for MEDLINE]
Free PMC Article

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