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

Journal of Nuclear Medicine

Andreas Kjaer¹  Michael Kjaer¹  Jacob Madsen¹  Dorthe Skovgaard¹ 

关键词: hypoxia;    ⁶⁴Cu-ATSM;    tendon;    skeletal muscle;    exercise;   

DOI  :  10.2967/jnumed.109.062216

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 64Cu-diacetyl bis(N4-methylthiosemicarbazone) (ATSM) and to quantitatively study concomitant changes in gene expression of 2 hypoxia-related genes, hypoxia-inducible factor 1α (HIF1α) 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, 64Cu-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 HIF1α and CAIII using real-time polymerase chain reaction. Results: Immediately after the contractions, uptake of 64Cu-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 HIF1α and CAIII, whereas this coherence was not found in tendons. Conclusion: We found enhanced uptake of 64Cu-ATSM in both early and late PET scans, thereby supporting the possibility that 64Cu-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 HIF1α and CAIII could indicate that healthy tendons are less responsive than skeletal muscles to low levels of oxygen.

【 授权许可】

Unknown