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Evaluation of the novel folate receptor ligand [18F]fluoro-PEG-folate for macrophage targeting in a rat model of arthritis

Overview of attention for article published in Arthritis Research & Therapy, January 2013
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50 Dimensions

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61 Mendeley
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Title
Evaluation of the novel folate receptor ligand [18F]fluoro-PEG-folate for macrophage targeting in a rat model of arthritis
Published in
Arthritis Research & Therapy, January 2013
DOI 10.1186/ar4191
Pubmed ID
Authors

Yoony YJ Gent, Karin Weijers, Carla FM Molthoff, Albert D Windhorst, Marc C Huisman, Desirée EC Smith, Sumith A Kularatne, Gerrit Jansen, Philip S Low, Adriaan A Lammertsma, Conny J van der Laken

Abstract

INTRODUCTION: Detection of (subclinical) synovitis is relevant for both early diagnosis and monitoring of therapy of rheumatoid arthritis (RA). Previously, the potential of imaging (sub)clinical arthritis was demonstrated by targeting the translocator protein in activated macrophages using (R)-[11C]PK11195 and positron emission tomography (PET). Images, however, also showed significant peri-articular background activity. The folate receptor (FR)-β is a potential alternative target for imaging activated macrophages. Therefore, the PET tracer [18F]fluoro-PEG-folate was synthesized and evaluated in both in vitro and ex vivo studies using a methylated BSA induced arthritis model. METHODS: [18F]fluoro-PEG-folate was synthesized in a two-step procedure. Relative binding affinities of non-radioactive fluoro-PEG-folate, folic acid and naturally circulating 5-methyltetrahydrofolate (5-Me-THF) to FR were determined using KB cells with high expression of FR. Both in vivo [18F]fluoro-PEG-folate PET and ex vivo tissue distribution studies were performed in arthritic and normal rats and results were compared with those of the established macrophage tracer (R)-[11C]PK11195. RESULTS: [18F]fluoro-PEG-folate was synthesized with a purity >97%, a yield of 300 to 1,700 MBq and a specific activity between 40 and 70 GBq/µmol. Relative in vitro binding affinity for FR of F-PEG-folate was 1.8-fold lower than that of folic acid, but 3-fold higher than that of 5-Me-THF. In the rat model, [18F]fluoro-PEG-folate uptake in arthritic knees was increased compared with both contralateral knees and knees of normal rats. Uptake in arthritic knees could be blocked by an excess of glucosamine-folate, consistent with [18F]fluoro-PEG-folate being specifically bound to FR. Arthritic knee-to-bone and arthritic knee-to-blood ratios of [18F]fluoro-PEG-folate were increased compared with those of (R)-[11C]PK11195. Reduction of 5-Me-THF levels in rat plasma to those mimicking human levels increased absolute [18F]fluoro-PEG-folate uptake in arthritic joints, but without improving target-to-background ratios. CONCLUSIONS: The novel PET tracer [18F]fluoro-PEG-folate, designed to target FR on activated macrophages provided improved contrast in a rat model of arthritis compared with the accepted macrophage tracer (R)-[11C]PK11195. These results warrant further exploration of [18F]fluoro-PEG-folate as a putative PET tracer for imaging (sub)clinical arthritis in RA patients.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Belgium 1 2%
Unknown 60 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 25%
Student > Master 9 15%
Other 7 11%
Student > Bachelor 5 8%
Researcher 4 7%
Other 14 23%
Unknown 7 11%
Readers by discipline Count As %
Medicine and Dentistry 17 28%
Chemistry 15 25%
Agricultural and Biological Sciences 7 11%
Pharmacology, Toxicology and Pharmaceutical Science 3 5%
Psychology 2 3%
Other 9 15%
Unknown 8 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 March 2013.
All research outputs
#7,813,286
of 12,451,992 outputs
Outputs from Arthritis Research & Therapy
#1,414
of 1,983 outputs
Outputs of similar age
#76,867
of 142,025 outputs
Outputs of similar age from Arthritis Research & Therapy
#5
of 8 outputs
Altmetric has tracked 12,451,992 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,983 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one is in the 20th percentile – i.e., 20% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 142,025 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 8 others from the same source and published within six weeks on either side of this one. This one has scored higher than 3 of them.