title: In vivo bioimaging as a novel strategy to detect doxorubicin-induced damage to gonadal blood vessels.
abstract: BACKGROUND
  Chemotherapy may induce deleterious effects in normal tissues, leading to organ damage. Direct vascular injury is the least characterized side effect. Our aim was to establish a real-time, in vivo molecular imaging platform for evaluating the potential vascular toxicity of doxorubicin in mice.
  
  
  METHODS
  Mice gonads served as reference organs. Mouse ovarian or testicular blood volume and femoral arterial blood flow were measured in real-time during and after doxorubicin (8 mg/kg intravenously) or paclitaxel (1.2 mg/kg) administration. Ovarian blood volume was imaged by ultrasound biomicroscopy (Vevo2100) with microbubbles as a contrast agent whereas testicular blood volume and blood flow as well as femoral arterial blood flow was imaged by pulse wave Doppler ultrasound. Visualization of ovarian and femoral microvasculature was obtained by fluorescence optical imaging system, equipped with a confocal fiber microscope (Cell-viZio).
  
  
  RESULTS
  Using microbubbles as a contrast agent revealed a 33% (P<0.01) decrease in ovarian blood volume already 3 minutes after doxorubicin injection. Doppler ultrasound depicted the same phenomenon in testicular blood volume and blood flow. The femoral arterial blood flow was impaired in the same fashion. Cell-viZio imaging depicted a pattern of vessels' injury at around the same time after doxorubicin injection: the wall of the blood vessels became irregular and the fluorescence signal displayed in the small vessels was gradually diminished. Paclitaxel had no vascular effect.
  
  
  CONCLUSIONS
  We have established a platform of innovative high-resolution molecular imaging, suitable for in vivo imaging of vessels' characteristics, arterial blood flow and organs blood volume that enable prolonged real-time detection of chemotherapy-induced effects in the same individuals. The acute reduction in gonadal and femoral blood flow and the impairment of the blood vessels wall may represent an acute universal doxorubicin-related vascular toxicity, an initial event in organ injury.
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Bar-Joseph
authors.forename: Irit
authors.initials: I
authors.lastname: Ben-Aharon
authors.forename: Moran
authors.initials: M
authors.lastname: Tzabari
authors.forename: Galia
authors.initials: G
authors.lastname: Tsarfaty
authors.forename: Salomon M
authors.initials: SM
authors.lastname: Stemmer
authors.forename: Ruth
authors.initials: R
authors.lastname: Shalgi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001775:Blood Circulation / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D057054:Molecular Imaging / Q000379:methods*; D010053:Ovary / Q000098:blood supply* / Q000187:drug effects; D013737:Testis / Q000098:blood supply* / Q000187:drug effects; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin