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Use of cis-[18F]fluoro-proline for assessment of exercise-related collagen synthesis in musculoskeletal connective tissue.

Skovgaard D, Kjaer A, Heinemeier KM, Brandt-Larsen M, Madsen J, Kjaer M - PLoS ONE (2011)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Sports Medicine Copenhagen, Bispebjerg Hospital and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. dskovgaard@dadlnet.dk

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.

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SUV of Cis-Fpro in the Exercise group in each of the musculoskeletal tissues.The SUV 60 minutes post injection did not change in any of the investigated tissues, when comparing pre- (open bars) and post-exercise (filled bars) PET scans. Likewise, no changes were found in the uptake of cis-Fpro 240 minutes post injection from the pre-exercise PET scan (open bars) to the post-exercise PETscan (filled bars). Values are mean ± SEM.
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pone-0016678-g003: SUV of Cis-Fpro in the Exercise group in each of the musculoskeletal tissues.The SUV 60 minutes post injection did not change in any of the investigated tissues, when comparing pre- (open bars) and post-exercise (filled bars) PET scans. Likewise, no changes were found in the uptake of cis-Fpro 240 minutes post injection from the pre-exercise PET scan (open bars) to the post-exercise PETscan (filled bars). Values are mean ± SEM.

Mentions: Cis-Fpro PET was obtained both before the three days of endurance exercise and 24 hours after the last exercise bout. Exercise did not change SUV in any of the investigated tissues, neither at one hour post injection (“cis-Fpro transport”), nor at four hours post injection (“cis-Fpro incorporation”) (figure 3). Likewise, SUV were constant in control group that were scanned twice interspersed with 8 days of normal cage activity. Furthermore, the image-derived results were confirmed by well counting on weighed tissue samples (based on tissues samples placed in RNAlater) from each rat. Also when relating counts/minute to tissue weight and injected dose no differences were found between the two groups (data not shown).


Use of cis-[18F]fluoro-proline for assessment of exercise-related collagen synthesis in musculoskeletal connective tissue.

Skovgaard D, Kjaer A, Heinemeier KM, Brandt-Larsen M, Madsen J, Kjaer M - PLoS ONE (2011)

SUV of Cis-Fpro in the Exercise group in each of the musculoskeletal tissues.The SUV 60 minutes post injection did not change in any of the investigated tissues, when comparing pre- (open bars) and post-exercise (filled bars) PET scans. Likewise, no changes were found in the uptake of cis-Fpro 240 minutes post injection from the pre-exercise PET scan (open bars) to the post-exercise PETscan (filled bars). Values are mean ± SEM.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3037959&req=5

pone-0016678-g003: SUV of Cis-Fpro in the Exercise group in each of the musculoskeletal tissues.The SUV 60 minutes post injection did not change in any of the investigated tissues, when comparing pre- (open bars) and post-exercise (filled bars) PET scans. Likewise, no changes were found in the uptake of cis-Fpro 240 minutes post injection from the pre-exercise PET scan (open bars) to the post-exercise PETscan (filled bars). Values are mean ± SEM.
Mentions: Cis-Fpro PET was obtained both before the three days of endurance exercise and 24 hours after the last exercise bout. Exercise did not change SUV in any of the investigated tissues, neither at one hour post injection (“cis-Fpro transport”), nor at four hours post injection (“cis-Fpro incorporation”) (figure 3). Likewise, SUV were constant in control group that were scanned twice interspersed with 8 days of normal cage activity. Furthermore, the image-derived results were confirmed by well counting on weighed tissue samples (based on tissues samples placed in RNAlater) from each rat. Also when relating counts/minute to tissue weight and injected dose no differences were found between the two groups (data not shown).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Sports Medicine Copenhagen, Bispebjerg Hospital and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. dskovgaard@dadlnet.dk

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.

Show MeSH
Related in: MedlinePlus