title: Tumor targeting and SPECT imaging properties of an (111)In-labeled galectin-3 binding peptide in prostate carcinoma.
abstract: BACKGROUND
  Galectin-3 (gal-3) is a carbohydrate binding protein that has been implicated in cell adhesion, tumor invasion and metastasis. The objective of this study was to evaluate the tumor targeting and imaging properties of a gal-3 binding peptide selected by phage display in a mouse model of metastatic human prostate carcinoma expressing gal-3.
  
  
  METHODS
  A gal-3 binding peptide, ANTPCGPYTHDCPVKR, was synthesized with a Gly-Ser-Gly (GSG) spacer and 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) and then radiolabeled with (111)In. The in vitro cell binding properties of (111)In-DOTA-(GSG)-ANTPCGPYTHDCPVKR were determined in metastatic human PC3-M prostate carcinoma cells. The pharmacokinetics and single-photon emission computed tomographic (SPECT/CT) imaging with the radiolabeled peptide were evaluated in SCID mice bearing human PC3-M prostate carcinoma tumor xenografts.
  
  
  RESULTS
  The radiolabeled peptide bound with a 50% inhibitory concentration of 191+/-10.2 nM to cultured PC3-M prostate carcinoma cells. In vivo tumor uptake and retention coupled with fast whole-body clearance of the peptide were demonstrated in PC3-M tumor-bearing SCID mice. The tumor uptake rates of the radiolabeled peptide were 1.27+/-0.10%ID/g at 30 min, 0.82+/-0.15%ID/g at 1 h and 0.57+/-0.09%ID/g at 2 h. MicroSPECT/CT studies revealed good tumor uptake of (111)In-DOTA-(GSG)-ANTPCGPYTHDCPVKR 2 h postinjection, while uptake in normal organs was low, with the exception of the kidneys.
  
  
  CONCLUSIONS
  In vitro cell binding along with tumor uptake of (111)In-DOTA-(GSG)-ANTPCGPYTHDCPVKR in PC3-M human prostate carcinoma tumor-bearing SCID mice suggests the potential of this peptide as a radiopharmaceutical for imaging of gal-3-expressing prostate tumors.
authors.affiliation: Department of Biochemistry, University of Missouri-Columbia School of Medicine, Columbia, MO 65211, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Deutscher
authors.forename: Said D
authors.initials: SD
authors.lastname: Figueroa
authors.forename: Senthil R
authors.initials: SR
authors.lastname: Kumar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm; D001667:Binding, Competitive; D014408:Biomarkers, Tumor; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D037502:Galectin 3 / Q000032:analysis; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007205:Indium Radioisotopes; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D016326:Extracellular Matrix Proteins
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D037502:Galectin 3; D006023:Glycoproteins; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins