title: Technetium-99m-labeled doxorubicin as an imaging probe for murine breast tumor (4T1 cell line) identification.
abstract: OBJECTIVE
  Early diagnosis of malignant tumors is essential to successfully plan a radical and curative approach. In this study we describe the direct radiolabeling of doxorubicin (DOX) at physiological pH to identify murine breast tumor (4T1 cells)-bearing BALB/c mice.
  
  
  METHODS
  Technetium-99m (99mTc) DOX was prepared by adding 99mTc-pertechnetate to a PBS (pH 7.4) solution containing DOX in the presence of stannous chloride. Radiochemical purity and in-vitro stability were determined. The circulation time of 99mTc-DOX was determined by measuring blood radioactivity in healthy animals. Scintigraphic images and biodistribution studies were carried out in tumor-bearing mice at 1, 4, and 8 h after injection.
  
  
  RESULTS
  The 99mTc-DOX complex showed high radiochemical purity (99.27 ± 0.34%) and in-vitro stability until 8 h. Tc-DOX levels in blood declined in a biphasic manner, with an α half-life of 4.5 min and a β half-life of 277.2 min. High uptake was achieved in kidneys, liver, and spleen, because of the drug elimination routes. Moreover, tumor uptake was higher than that of control tissue, resulting in high tumor-to-muscle ratios.
  
  
  CONCLUSIONS
  DOX was successfully labeled with 99mTc-pertechnetate and showed high stability. Biodistribution and scintigraphic studies indicated high tumor-to-muscle ratios in breast tumor-bearing BALB/c mice. These results suggested the feasibility of 99mTc-DOX as a functional agent in tumor diagnosis.
authors.affiliation: aDepartments of Clinical and Toxicological Analyses bPharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil cDepartment of Nuclear Medicine, Radiology, NeuroRadiology, Medical Physics, Clinical Laboratory, Microbiology, Pathology, Santa Maria della Misericordia Hospital, Rovigo, Italy.
authors.forename: Renata S
authors.initials: RS
authors.lastname: Fernandes
authors.forename: Juliana de Oliveira
authors.initials: Jde O
authors.lastname: Silva
authors.forename: Savia C A
authors.initials: SC
authors.lastname: Lopes
authors.forename: Sotirios
authors.initials: S
authors.lastname: Chondrogiannis
authors.forename: Domenico
authors.initials: D
authors.lastname: Rubello
authors.forename: Valbert N
authors.initials: VN
authors.lastname: Cardoso
authors.forename: Mônica C
authors.initials: MC
authors.lastname: Oliveira
authors.forename: Lucas A M
authors.initials: LA
authors.lastname: Ferreira
authors.forename: André L B
authors.initials: AL
authors.lastname: de Barros
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D005260:Female; D006863:Hydrogen-Ion Concentration; D007553:Isotope Labeling; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000473:pathology*; D051379:Mice; D011854:Radiochemistry; D011877:Radionuclide Imaging; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D013667:Technetium; D004317:Doxorubicin