title: Assessing p-glycoprotein (Pgp) activity in vivo utilizing 68Ga-Schiff base complexes.
abstract: OBJECTIVE
  The p-glycoprotein (Pgp) is the most prominent member of active drug transporters leading to a multidrug-resistant phenotype. For identification of tumors functionally overexpressing Pgp in vivo, non-invasive imaging techniques are needed.
  
  
  METHODS
  Six Schiff base compounds were synthesized and labeled with (68)Ge/(68)Ga generator-derived (68)Ga. The compounds were studied in vitro in Pgp-positive tumor cells. The property of being a Pgp substrate was tested by comparison of the tracers uptake in R-3327 Dunning prostate carcinoma AT1 cells in presence and absence of the Pgp-inhibitor verapamil. In vivo investigations were performed with tumor-bearing rats imaged with micro-positron emission tomography.
  
  
  RESULTS
  All ligands were labeled with (68)Ga in yields of >92% beside one (~55%). The tracers showed different accumulation within the cells in vitro (4-60%). In blocking experiments, the ratio (blocked to unblocked) varied from 1.8 to 1.0. For in vivo experiments, (68)Ga-ENBDMPI and (68)Ga-MFL6.MZ were selected. The tumors showed specific uptake of the tracer. Direct intratumoral injection of verapamil increased the tracer concentration by ~25% reflecting the functional Pgp activity.
  
  
  CONCLUSIONS
  Two (68)Ga-labeled ligands appear to be valuable for imaging non-invasively the intratumoral Pgp activity. On a long term, patients with multidrug-resistant tumors pre-therapeutically may be identified prior to treatment.
authors.affiliation: Institute of Nuclear Chemistry, University of Mainz, Mainz, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Fellner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dillenburg
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Buchholz
authors.forename: Nicole
authors.initials: N
authors.lastname: Bausbacher
authors.forename: Mathias
authors.initials: M
authors.lastname: Schreckenberger
authors.forename: Franz
authors.initials: F
authors.lastname: Renz
authors.forename: Frank
authors.initials: F
authors.lastname: Rösch
authors.forename: Oliver
authors.initials: O
authors.lastname: Thews
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D005708:Gallium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D012545:Schiff Bases
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012545:Schiff Bases; D005708:Gallium
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