Micro Regional Heterogeneity of 64Cu-ATSM and 18F-FDG Uptake in Canine Soft Tissue Sarcomas: Relation to Cell Proliferation, Hypoxia and Glycolysis

• Published in: PloS one 2015, Vol.10 (10), p.e0141379-e0141379
• Main Authors: Zornhagen, Kamilla Westarp, Hansen, Anders E, Oxboel, Jytte, Clemmensen, Andreas E, El Ali, Henrik H, Kristensen, Annemarie T, Kjær, Andreas
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animal sciences; Animals; Autoradiography; Cancer; Cell growth; Cell proliferation; Cell Proliferation - physiology; Copper Radioisotopes; Correlation; Developmental biology; Dogs; Fluorodeoxyglucose F18; Gene expression; Glycolysis; Glycolysis - physiology; Heterogeneity; Hypoxia; Hypoxia - physiopathology; Immunohistochemistry; Ki-67 gene; Lung cancer; Markers; Medical imaging; Medical prognosis; Nuclear medicine; Physiology; Pixels; Positron-Emission Tomography; Radioactivity; Sarcoma; Sarcoma - diagnosis; Solid tumors; Spatial distribution; Tissue; Tissues; Tracers; Tumor microenvironment; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0141379

Tumour microenvironment heterogeneity is believed to play a key role in cancer progression and therapy resistance. However, little is known about micro regional distribution of hypoxia, glycolysis and proliferation in spontaneous solid tumours. The overall aim was simultaneous investigation of micro regional heterogeneity of 64Cu-ATSM (hypoxia) and 18F-FDG (glycolysis) uptake and correlation to endogenous markers of hypoxia, glycolysis, proliferation and angiogenesis to better therapeutically target aggressive tumour regions and prognosticate outcome. Exploiting the different half-lives of 64Cu-ATSM (13 h) and 18F-FDG (2 h) enabled simultaneous investigation of micro regional distribution of hypoxia and glycolysis in 145 tumour pieces from four spontaneous canine soft tissue sarcomas. Pairwise measurements of radioactivity and gene expression of endogenous markers of hypoxia (HIF-1α, CAIX), glycolysis (HK2, GLUT1 and GLUT3), proliferation (Ki-67) and angiogenesis (VEGFA and TF) were performed. Dual tracer autoradiography was compared with Ki-67 immunohistochemistry. Micro regional heterogeneity in hypoxia and glycolysis within and between tumour sections of each tumour piece was observed. The spatial distribution of 64Cu-ATSM and 18F-FDG was rather similar within each tumour section as reflected in moderate positive significant correlations between the two tracers (ρ = 0.3920-0.7807; p = 0.0180 -