title: Tumour hypoxia and technetium tracers: in vivo studies.
abstract: BACKGROUND
  Hypoxia is a biochemical condition where reduced oxygen partial pressure at tissue level occurs. This metabolic situation can lead to resistance to radio and chemotherapy. In malignant solid tumours, hypoxia is a common characteristic, having a great impact at biological level, being of tremendous importance for complete understanding of tumour progression.
  
  
  OBJECTIVE
  We studied the behavior of 99mTc-HL91 in vivo, using an animal model based on Balb-c nu/nu mice with a xenotransplant of the human colorectal adenocarcinoma cell line, WiDr.
  
  
  METHODS
  In vivo studies using an animal model of xenograft on Balb/c nu/nu nude mice were carried out. This model, allowed us to evaluate the radiopharmaceutical biodistribution and to calculate tumour/muscle ratio, acquired after 99mTc-HL91 injection. We also performed ex vivo studies, using the excised tumours to access viability and to characterize the intracellular production of reactive oxygen species and the status of mitochondrial membrane potential through flow cytometry.
  
  
  CONCLUSIONS
  The biodistribution after 99mTc-HL91 injection showed urinary and hepatobilliary excretion in similar proportions and tumour uptake around 4.4% of administered activity. This uptake was higher at the bigger tumours. Through flow cytometry we observed that larger tumours have a higher amount of reactive oxygen species and a decrease in mitochondrial membrane potential.
  
  
  CONCLUSIONS
  99mTc-HL91 allowed a non-invasive evaluation of the solid tumours oxidative state by nuclear medicine functional imaging. This information can be of high importance at the pre-treatment estimation of this type of tumours.
authors.affiliation: Biophysics/Biomatematics Institute, IBILI, Faculty of Medicine, University of Coimbra, Portugal. mabrantes@ibili.uc.pt
authors.forename: A M
authors.initials: AM
authors.lastname: Abrantes
authors.forename: E
authors.initials: E
authors.lastname: Serra
authors.forename: C
authors.initials: C
authors.lastname: Goncalves
authors.forename: B
authors.initials: B
authors.lastname: Oliveiros
authors.forename: M
authors.initials: M
authors.lastname: Laranjo
authors.forename: A B
authors.initials: AB
authors.lastname: Sarmento-Ribeiro
authors.forename: A
authors.initials: A
authors.lastname: Rocha-Gonsalves
authors.forename: M F
authors.initials: MF
authors.lastname: Botelho
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D010091:Oximes / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D015609:Organotechnetium Compounds; D010091:Oximes; D019275:Radiopharmaceuticals; D017382:Reactive Oxygen Species; C105527:technetium Tc 99m 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime