Noninvasive Cu-64-ATSM and PET/CT Assessment of Hypoxia in Rat Skeletal Muscles and Tendons During Muscle Contractions

D. Skovgaard; M. Kjaer; J. Madsen; A. Kjaer

Noninvasive Cu-64-ATSM and PET/CT Assessment of Hypoxia in Rat Skeletal Muscles and Tendons During Muscle Contractions

D. Skovgaard, M. Kjaer, J. Madsen, A. Kjaer

Damage and Repair

8 Citationer (Scopus)

Abstract

The purpose of the present study was to investigate exercise-related changes in oxygenation in rat skeletal muscles and tendons noninvasively with PET/CT and the hypoxia-selective tracer Cu-64-diacetyl bis(N-4-methylthiosemicarbazone) (ATSM) and to quantitatively study concomitant changes in gene expression of 2 hypoxia-related genes, hypoxia-inducible factor 1 alpha (HIF1 alpha) and carbonic anhydrase III (CAIII). Methods: Two groups of Wistar rats performed 1-leg contractions of the calf muscle by electrostimulation of the sciatic nerve. After 10 min of muscle contractions, Cu-64-ATSM was injected and contractions were continued for 20 min. PET/CT of both hind limbs was performed immediately and 1 h after the contractions. The exercise group (n = 8) performed only muscle contractions as described, whereas the other group, exercise plus cuff (n = 8), in addition underwent cuff-induced hypoxia during the first PET/CT scan. Standardized uptake values (SUVs) were calculated for the Achilles tendons and triceps surae muscles and were correlated to gene expression of HIF1 alpha and CAIII using real-time polymerase chain reaction. Results: Immediately after the contractions, uptake of Cu-64-ATSM was significantly increased, by approximately 1.5-fold in muscles and 1.3-fold in tendons, compared with resting conditions. The significant increase was maintained in late PET scans in stimulated muscles and tendons independently of cuff application. In muscles, SUV correlated significantly with gene expression of HIF1 alpha and CAIII, whereas this coherence was not found in tendons. Conclusion: We found enhanced uptake of Cu-64-ATSM in both early and late PET scans, thereby supporting the possibility that Cu-64-ATSM registers exercise-induced transient hypoxia in both skeletal muscles and force-transmitting tendons. The fact that skeletal muscles but not tendons showed upregulation of HIF1 alpha and CAIII could indicate that healthy tendons are less responsive than skeletal muscles to low levels of oxygen
Udgivelsesdato: 2009

Originalsprog	Engelsk
Tidsskrift	Journal of Nuclear Medicine
Vol/bind	50
Udgave nummer	6
Sider (fra-til)	950-958
Antal sider	9
ISSN	0161-5505
Status	Udgivet - 2009

Citationsformater

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title = "Noninvasive Cu-64-ATSM and PET/CT Assessment of Hypoxia in Rat Skeletal Muscles and Tendons During Muscle Contractions",

abstract = "The purpose of the present study was to investigate exercise-related changes in oxygenation in rat skeletal muscles and tendons noninvasively with PET/CT and the hypoxia-selective tracer Cu-64-diacetyl bis(N-4-methylthiosemicarbazone) (ATSM) and to quantitatively study concomitant changes in gene expression of 2 hypoxia-related genes, hypoxia-inducible factor 1 alpha (HIF1 alpha) and carbonic anhydrase III (CAIII). Methods: Two groups of Wistar rats performed 1-leg contractions of the calf muscle by electrostimulation of the sciatic nerve. After 10 min of muscle contractions, Cu-64-ATSM was injected and contractions were continued for 20 min. PET/CT of both hind limbs was performed immediately and 1 h after the contractions. The exercise group (n = 8) performed only muscle contractions as described, whereas the other group, exercise plus cuff (n = 8), in addition underwent cuff-induced hypoxia during the first PET/CT scan. Standardized uptake values (SUVs) were calculated for the Achilles tendons and triceps surae muscles and were correlated to gene expression of HIF1 alpha and CAIII using real-time polymerase chain reaction. Results: Immediately after the contractions, uptake of Cu-64-ATSM was significantly increased, by approximately 1.5-fold in muscles and 1.3-fold in tendons, compared with resting conditions. The significant increase was maintained in late PET scans in stimulated muscles and tendons independently of cuff application. In muscles, SUV correlated significantly with gene expression of HIF1 alpha and CAIII, whereas this coherence was not found in tendons. Conclusion: We found enhanced uptake of Cu-64-ATSM in both early and late PET scans, thereby supporting the possibility that Cu-64-ATSM registers exercise-induced transient hypoxia in both skeletal muscles and force-transmitting tendons. The fact that skeletal muscles but not tendons showed upregulation of HIF1 alpha and CAIII could indicate that healthy tendons are less responsive than skeletal muscles to low levels of oxygen Udgivelsesdato: 2009",

author = "D. Skovgaard and M. Kjaer and J. Madsen and A. Kjaer",

note = "Times Cited: 0ArticleEnglishSkovgaard, DBispebjerg Hosp, Inst Sports Med, Bispebjerg Bakke 23, DK-2400 Copenhagen, DenmarkCited References Count: 40529ALSOC NUCLEAR MEDICINE INC1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USARESTON",

year = "2009",

language = "English",

volume = "50",

pages = "950--958",

journal = "The Journal of Nuclear Medicine",

issn = "0161-5505",

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TY - JOUR

T1 - Noninvasive Cu-64-ATSM and PET/CT Assessment of Hypoxia in Rat Skeletal Muscles and Tendons During Muscle Contractions

AU - Skovgaard, D.

AU - Kjaer, M.

AU - Madsen, J.

AU - Kjaer, A.

N1 - Times Cited: 0ArticleEnglishSkovgaard, DBispebjerg Hosp, Inst Sports Med, Bispebjerg Bakke 23, DK-2400 Copenhagen, DenmarkCited References Count: 40529ALSOC NUCLEAR MEDICINE INC1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USARESTON

PY - 2009

Y1 - 2009

N2 - The purpose of the present study was to investigate exercise-related changes in oxygenation in rat skeletal muscles and tendons noninvasively with PET/CT and the hypoxia-selective tracer Cu-64-diacetyl bis(N-4-methylthiosemicarbazone) (ATSM) and to quantitatively study concomitant changes in gene expression of 2 hypoxia-related genes, hypoxia-inducible factor 1 alpha (HIF1 alpha) and carbonic anhydrase III (CAIII). Methods: Two groups of Wistar rats performed 1-leg contractions of the calf muscle by electrostimulation of the sciatic nerve. After 10 min of muscle contractions, Cu-64-ATSM was injected and contractions were continued for 20 min. PET/CT of both hind limbs was performed immediately and 1 h after the contractions. The exercise group (n = 8) performed only muscle contractions as described, whereas the other group, exercise plus cuff (n = 8), in addition underwent cuff-induced hypoxia during the first PET/CT scan. Standardized uptake values (SUVs) were calculated for the Achilles tendons and triceps surae muscles and were correlated to gene expression of HIF1 alpha and CAIII using real-time polymerase chain reaction. Results: Immediately after the contractions, uptake of Cu-64-ATSM was significantly increased, by approximately 1.5-fold in muscles and 1.3-fold in tendons, compared with resting conditions. The significant increase was maintained in late PET scans in stimulated muscles and tendons independently of cuff application. In muscles, SUV correlated significantly with gene expression of HIF1 alpha and CAIII, whereas this coherence was not found in tendons. Conclusion: We found enhanced uptake of Cu-64-ATSM in both early and late PET scans, thereby supporting the possibility that Cu-64-ATSM registers exercise-induced transient hypoxia in both skeletal muscles and force-transmitting tendons. The fact that skeletal muscles but not tendons showed upregulation of HIF1 alpha and CAIII could indicate that healthy tendons are less responsive than skeletal muscles to low levels of oxygen Udgivelsesdato: 2009

AB - The purpose of the present study was to investigate exercise-related changes in oxygenation in rat skeletal muscles and tendons noninvasively with PET/CT and the hypoxia-selective tracer Cu-64-diacetyl bis(N-4-methylthiosemicarbazone) (ATSM) and to quantitatively study concomitant changes in gene expression of 2 hypoxia-related genes, hypoxia-inducible factor 1 alpha (HIF1 alpha) and carbonic anhydrase III (CAIII). Methods: Two groups of Wistar rats performed 1-leg contractions of the calf muscle by electrostimulation of the sciatic nerve. After 10 min of muscle contractions, Cu-64-ATSM was injected and contractions were continued for 20 min. PET/CT of both hind limbs was performed immediately and 1 h after the contractions. The exercise group (n = 8) performed only muscle contractions as described, whereas the other group, exercise plus cuff (n = 8), in addition underwent cuff-induced hypoxia during the first PET/CT scan. Standardized uptake values (SUVs) were calculated for the Achilles tendons and triceps surae muscles and were correlated to gene expression of HIF1 alpha and CAIII using real-time polymerase chain reaction. Results: Immediately after the contractions, uptake of Cu-64-ATSM was significantly increased, by approximately 1.5-fold in muscles and 1.3-fold in tendons, compared with resting conditions. The significant increase was maintained in late PET scans in stimulated muscles and tendons independently of cuff application. In muscles, SUV correlated significantly with gene expression of HIF1 alpha and CAIII, whereas this coherence was not found in tendons. Conclusion: We found enhanced uptake of Cu-64-ATSM in both early and late PET scans, thereby supporting the possibility that Cu-64-ATSM registers exercise-induced transient hypoxia in both skeletal muscles and force-transmitting tendons. The fact that skeletal muscles but not tendons showed upregulation of HIF1 alpha and CAIII could indicate that healthy tendons are less responsive than skeletal muscles to low levels of oxygen Udgivelsesdato: 2009

M3 - Journal article

SN - 0161-5505

VL - 50

SP - 950

EP - 958

JO - The Journal of Nuclear Medicine

JF - The Journal of Nuclear Medicine

IS - 6

ER -