title: Use of cis-[18F]fluoro-proline for assessment of exercise-related collagen synthesis in musculoskeletal connective tissue.
abstract: Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[(18)F]fluoro-proline (cis-Fpro), for non-invasive assessment of collagen synthesis in rat musculoskeletal tissues at rest and following short-term (3 days) treadmill running. Musculoskeletal collagen synthesis was studied in rats at rest and 24 h post-exercise. At each session, rats were PET scanned at two time points following injection of cis-FPro: (60 and 240 min p.i). SUV were calculated for Achilles tendon, calf muscle and tibial bone. The PET-derived results were compared to mRNA expression of collagen type I and III. Tibial bone had the highest SUV that increased significantly (p<0.001) from the early (60 min) to the late (240 min) PET scan, while SUV in tendon and muscle decreased (p<0.001). Exercise had no influence on SUV, which was contradicted by an increased gene expression of collagen type I and III in muscle and tendon. The clearly, visible uptake of cis-Fpro in the collagen-rich musculoskeletal tissues is promising for multi-tissue studies in vivo. The tissue-specific differences with the highest basal uptake in bone are in accordance with earlier studies relying on tissue incorporation of isotopic-labelled proline. A possible explanation of the failure to demonstrate enhanced collagen synthesis following exercise, despite augmented collagen type I and III transcription, is that SUV calculations are not sensitive enough to detect minor changes in collagen synthesis. Further studies including kinetic compartment modeling must be performed to establish whether cis-Fpro can be used for non-invasive in-vivo assessment of exercise-induced changes in musculoskeletal collagen synthesis.
authors.affiliation: Institute of Sports Medicine Copenhagen, Bispebjerg Hospital and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. dskovgaard@dadlnet.dk
authors.forename: Dorthe
authors.initials: D
authors.lastname: Skovgaard
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjaer
authors.forename: Katja Maria
authors.initials: KM
authors.lastname: Heinemeier
authors.forename: Malene
authors.initials: M
authors.lastname: Brandt-Larsen
authors.forename: Jacob
authors.initials: J
authors.lastname: Madsen
authors.forename: Michael
authors.initials: M
authors.lastname: Kjaer
mesh_terms: D000818:Animals; D001692:Biological Transport; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D003238:Connective Tissue / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D049268:Positron-Emission Tomography / Q000379:methods*; D011392:Proline / Q000031:analogs & derivatives*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D012146:Rest; D013710:Tendons / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D012333:RNA, Messenger; C431803:fluoro-proline; D003094:Collagen; D011392:Proline