title: Hepato and Cardiotoxicity of Chemotherapeutic Treatment Evaluated by Means of Small Animal Imaging.
abstract: BACKGROUND
  Chemotherapy is one of the most common approaches for cancer treatment. Particularly Doxorubicin has been proven to be effective in the treatment of many soft and solid tumors for locally advanced and metastatic cancer. It is not easy to clinically evaluate the chemotoxic or chemoprotective effect of some drugs, even more when there is a subclinical toxicity.
  
  
  OBJECTIVE
  To determine the usefulness of the hepatobiliary, colloid and cardiac scintigraphies, employing99mTcdisida, 99mTc-phytate and 99mTc-sestamibi respectively, in the evaluation of the hepato and cardiotoxicity of two chemotherapeutic treatments assessed in rats.
  
  
  METHODS
  Two groups were submitted to doxorubicin (DOX) treatment and one was co-administered with histamine (DOX+HIS). Static 99mTc-phytate and 99mTc-sestamibi scintigraphies as well as a dynamic 99mTc-disida study were performed in a small field of view gamma camera at: 0 weeks (control), 1 week and 2 weeks of treatment. Imagenological parameters were calculated: Liver/Bone Marrow ratio (L/BM), Heart/Background ratio (H/B) and time to the maximum (Tmax) for 99mTc-phytate, 99mTc-sestamibi and 99mTc-disida extraction, respectively.
  
  
  RESULTS
  Control (L/BM= 98±3; H/B=2.3±0.4; Tmax=8±3), DOX (L/BM: 85±3, 80±3; H/B, 3.5±0.5, 3.3±0.5 and Tmax 6±1, 4±1) for 1 and 2 weeks respectively and DOX+HIS (L/BM: 99±0.3, 98±1; H/B 2.9±0.5, 2.9±0.5 and Tmax, 8±2, 9±2) for 1 and 2 weeks, respectively. Histological analysis showed cardio and hepatotoxicity induced by doxorubicin.
  
  
  CONCLUSIONS
  Imagenological parameters showed differences among treated and control groups and between both chemotherapy treatments. Thus, these radiopharmaceutical functional approaches were able to reflect heart and liver toxicity produced by doxorubicin.
authors.affiliation: Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, Universidad de Buenos Aires, Buenos Aires, Argentina, Junin 956, Buenos Aires 1113, Argentina.
authors.forename: Fiorella Carla
authors.initials: FC
authors.lastname: Tesan
authors.affiliation: Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Mariano Gaston
authors.initials: MG
authors.lastname: Portillo
authors.affiliation: Laboratory of Cellular and Molecular Biology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina, Argentina.
authors.forename: Diego
authors.initials: D
authors.lastname: Martinel-Lamas
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Vanina Araceli
authors.initials: VA
authors.lastname: Medina
authors.affiliation: Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Maria Jimena
authors.initials: MJ
authors.lastname: Salgueiro
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Marcela Beatriz
authors.initials: MB
authors.lastname: Zubillaga
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D066126:Cardiotoxicity; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006321:Heart / Q000187:drug effects*; D006632:Histamine / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D006632:Histamine
keywords: 99mTc-disida; 99mTc-phytate; 99mTc-sestamibi; Doxorubicin; cardiotoxicity; hepatotoxicity; small animal imaging