title: Evaluation of 99mTc-glucarate as a breast cancer imaging agent in a xenograft animal model.
abstract: BACKGROUND
  The use of [(99m)Tc]glucarate has been reported as an infarct-avid agent with the potential for very early detection of myocardial infarction. [(99m)Tc]Glucarate has also been postulated as an agent for non-invasive detection of tumors. The aim of our study was to develop a Glucarate kit and evaluate [(99m)Tc]glucarate as a potential cancer imaging agent in female SCID mice bearing human MDA-MB-435 breast tumors.
  
  
  METHODS
  Glucarate in a kit formulation was labeled with (99m)Tc and evaluated for radiolabelling efficiency and radiochemical purity. The Glucarate kit stability was assessed by monthly quality controls. The pharmacokinetics of [(99m)Tc]glucarate were determined in female SCID mice bearing MDA-MB-435 human breast carcinoma tumors at 0.5, 1, 2, 4 and 24 h. Nuclear imaging studies were performed with a micro-single photon emission tomography (SPECT)/computed tomography (CT) system at 2 h post injection, while magnetic resonance imaging (MRI) was employed for tumor morphology analysis and metastatic deposit localization.
  
  
  RESULTS
  The Glucarate kits exhibited a stable shelf life of 6 months. [(99m)Tc]Glucarate was obtained with radiochemical purity greater than 95%. Biodistribution studies demonstrated moderate tumor uptake coupled with high renal clearance. Tumor-to-muscle ratios were 4.85 and 5.14 at 1 and 4 h post injection. MRI analysis showed tumors with dense cellular growth and moderate central necrosis. [(99m)Tc]Glucarate uptake in the primary MDA-MB-435 shoulder tumors and metastatic lesions were clearly visualized with micro-SPECT/CT imaging.
  
  
  CONCLUSIONS
  Selective tumor uptake and rapid clearance from nontarget organs makes [(99m)Tc]glucarate a potential agent for breast cancer imaging that awaits validation in a clinical trial.
authors.affiliation: Nuclear Medicine Center, Clinical Hospital, University of Uruguay, Montevideo, 11600 Uruguay.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Gambini
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabral
authors.forename: Omar
authors.initials: O
authors.lastname: Alonso
authors.forename: Eduardo
authors.initials: E
authors.lastname: Savio
authors.forename: Said Daibes
authors.initials: SD
authors.lastname: Figueroa
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.forename: Lixin
authors.initials: L
authors.lastname: Ma
authors.forename: Susan L
authors.initials: SL
authors.lastname: Deutscher
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Quinn
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D015609:Organotechnetium Compounds; C067171:technetium Tc 99m glucarate; D005937:Glucaric Acid