Hypoxia-induced redox alterations and their correlation with 99mTc-MIBI and 99mTc-HL-91 uptake in colon cancer cells.
Colorectal cancer is one of the most common malignancies in the Western world and is an example of a solid tumour in which hypoxia is a common feature and develops because of the inability of the vascular system to supply adequate amounts of oxygen to growing tumours. Hypoxia effects on tumour cell biology can be detected and characterized using different methods. The use of imaging with gamma-emitting radionuclides to detect hypoxic tissue was first suggested by Chapman in 1979 [N Engl J Med 301 (1979) 1429-1432]. (99m)Tc-4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime, also known as (99m)Tc-HL-91, has been among the most studied hypoxia markers. The objective of this study was to correlate the uptake of (99m)Tc-HL-91 and (99m)Tc-MIBI in colon cancer cells under normoxic and hypoxic conditions and to compare this information with some parameters such as oxidative stress and mitochondrial dysfunction of the cells analyzed by flow cytometry. Our results show that the in vitro (99m)Tc-HL-91 uptake is higher in hypoxic conditions, which is confirmed by the decreased uptake of (99m)Tc-MIBI. Flow cytometry results demonstrate that hypoxic conditions used are not enough to induce cellular death, but are responsible for the alterations in the intracellular redox environment, namely, increase of ROS production, proteic pimonidazol-derived adduct formation and alteration in the mitochondrial membrane permeability. Therefore, these results confirm that (99m)Tc-HL-91 is a radiopharmaceutical with favourable characteristics for detecting hypoxia.
Biophysics/Biomathematics Institute, IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal. mabrantes@ibili.uc.pt
Ana Margarida
AM
Abrantes
Maria Elisa Silva
ME
Serra
Ana Cristina
AC
Gonçalves
Joana
J
Rio
Bárbara
B
Oliveiros
Mafalda
M
Laranjo
António Manuel
AM
Rocha-Gonsalves
Ana Bela
AB
Sarmento-Ribeiro
Maria Filomena
MF
Botelho
D000818:Animals; D001692:Biological Transport; D016923:Cell Death; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D015609:Organotechnetium Compounds / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010091:Oximes / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017256:Technetium Tc 99m Sestamibi / Q000378:metabolism*
D015609:Organotechnetium Compounds; D010091:Oximes; D017382:Reactive Oxygen Species; C105527:technetium Tc 99m 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime; D017256:Technetium Tc 99m Sestamibi