Sustained Macrophage Infiltration upon Multiple Intra-Articular Injections: An Improved Rat Model of Rheumatoid Arthritis for PET Guided Therapy Evaluation

To widen the therapeutic window for PET guided evaluation of novel anti-RA agents, modifications were made in a rat model of rheumatoid arthritis (RA). Arthritis was induced in the right knee of Wistar rats with repeated boosting to prolong articular inflammation. The contralateral knee served as co...

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Main Authors:	Chandrupatla, Durga M. S. H., Weijers, Karin, Gent, Yoony Y. J., de Greeuw, Inge, Lammertsma, Adriaan A., Jansen, Gerrit, van der Laken, Conny J., Molthoff, Carla F. M.
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324741/

id	pubmed-4324741
recordtype	oai_dc
spelling	pubmed-43247412015-02-18 Sustained Macrophage Infiltration upon Multiple Intra-Articular Injections: An Improved Rat Model of Rheumatoid Arthritis for PET Guided Therapy Evaluation Chandrupatla, Durga M. S. H. Weijers, Karin Gent, Yoony Y. J. de Greeuw, Inge Lammertsma, Adriaan A. Jansen, Gerrit van der Laken, Conny J. Molthoff, Carla F. M. Research Article To widen the therapeutic window for PET guided evaluation of novel anti-RA agents, modifications were made in a rat model of rheumatoid arthritis (RA). Arthritis was induced in the right knee of Wistar rats with repeated boosting to prolong articular inflammation. The contralateral knee served as control. After immunization with methylated bovine serum albumin (mBSA) in complete Freund's adjuvant and custom Bordetella pertussis antigen, one or more intra-articular (i.a.) mBSA injections were given over time in the right knee. Serum anti-mBSA antibodies, DTH response, knee thickness, motion, and synovial macrophages were analyzed and [18F]FDG(-general inflammation) and (R)-[11C]PK11195 (macrophages-)PET was performed followed by ex vivo tissue distribution. Significant anti-mBSA levels, DTH, swelling of arthritic knee, and sustained and prolonged macrophage infiltration in synovial tissue were found, especially using multiple i.a. injections. Increased [18F]FDG and (R)-[11C]PK11195 accumulation was demonstrated in arthritic knees as compared to contralateral knees, which was confirmed in ex vivo tissue distribution studies. Boosting proved advantageous for achieving a chronic model without remission. The model will offer excellent opportunities for repeated PET studies to monitor progression of disease and efficacy of novel therapeutic agents for RA in the same animal. Hindawi Publishing Corporation 2015 2015-01-28 /pmc/articles/PMC4324741/ /pubmed/25695087 http://dx.doi.org/10.1155/2015/509295 Text en Copyright © 2015 Durga M. S. H. Chandrupatla et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chandrupatla, Durga M. S. H. Weijers, Karin Gent, Yoony Y. J. de Greeuw, Inge Lammertsma, Adriaan A. Jansen, Gerrit van der Laken, Conny J. Molthoff, Carla F. M.
spellingShingle	Chandrupatla, Durga M. S. H. Weijers, Karin Gent, Yoony Y. J. de Greeuw, Inge Lammertsma, Adriaan A. Jansen, Gerrit van der Laken, Conny J. Molthoff, Carla F. M. Sustained Macrophage Infiltration upon Multiple Intra-Articular Injections: An Improved Rat Model of Rheumatoid Arthritis for PET Guided Therapy Evaluation
author_facet	Chandrupatla, Durga M. S. H. Weijers, Karin Gent, Yoony Y. J. de Greeuw, Inge Lammertsma, Adriaan A. Jansen, Gerrit van der Laken, Conny J. Molthoff, Carla F. M.
author_sort	Chandrupatla, Durga M. S. H.
title	Sustained Macrophage Infiltration upon Multiple Intra-Articular Injections: An Improved Rat Model of Rheumatoid Arthritis for PET Guided Therapy Evaluation
title_short	Sustained Macrophage Infiltration upon Multiple Intra-Articular Injections: An Improved Rat Model of Rheumatoid Arthritis for PET Guided Therapy Evaluation
title_full	Sustained Macrophage Infiltration upon Multiple Intra-Articular Injections: An Improved Rat Model of Rheumatoid Arthritis for PET Guided Therapy Evaluation
title_fullStr	Sustained Macrophage Infiltration upon Multiple Intra-Articular Injections: An Improved Rat Model of Rheumatoid Arthritis for PET Guided Therapy Evaluation
title_full_unstemmed	Sustained Macrophage Infiltration upon Multiple Intra-Articular Injections: An Improved Rat Model of Rheumatoid Arthritis for PET Guided Therapy Evaluation
title_sort	sustained macrophage infiltration upon multiple intra-articular injections: an improved rat model of rheumatoid arthritis for pet guided therapy evaluation
description	To widen the therapeutic window for PET guided evaluation of novel anti-RA agents, modifications were made in a rat model of rheumatoid arthritis (RA). Arthritis was induced in the right knee of Wistar rats with repeated boosting to prolong articular inflammation. The contralateral knee served as control. After immunization with methylated bovine serum albumin (mBSA) in complete Freund's adjuvant and custom Bordetella pertussis antigen, one or more intra-articular (i.a.) mBSA injections were given over time in the right knee. Serum anti-mBSA antibodies, DTH response, knee thickness, motion, and synovial macrophages were analyzed and [18F]FDG(-general inflammation) and (R)-[11C]PK11195 (macrophages-)PET was performed followed by ex vivo tissue distribution. Significant anti-mBSA levels, DTH, swelling of arthritic knee, and sustained and prolonged macrophage infiltration in synovial tissue were found, especially using multiple i.a. injections. Increased [18F]FDG and (R)-[11C]PK11195 accumulation was demonstrated in arthritic knees as compared to contralateral knees, which was confirmed in ex vivo tissue distribution studies. Boosting proved advantageous for achieving a chronic model without remission. The model will offer excellent opportunities for repeated PET studies to monitor progression of disease and efficacy of novel therapeutic agents for RA in the same animal.
publisher	Hindawi Publishing Corporation
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324741/
_version_	1613186867844349952

Sustained Macrophage Infiltration upon Multiple Intra-Articular Injections: An Improved Rat Model of Rheumatoid Arthritis for PET Guided Therapy Evaluation

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