title: Structural modifications of ⁹⁹mTc-labelled bombesin-like peptides for optimizing pharmacokinetics in prostate tumor targeting.
abstract: OBJECTIVE
  The main goal of the present study was to investigate the importance of the addition of a positively charged aa in the naturally occurring bombesin (BN) peptide for its utilization as radiodiagnostic agent, taking into consideration the biodistribution profile, the pharmacokinetic characteristics and the tumor targeting ability.
  
  
  METHODS
  Two BN-derivatives of the general structure [M-chelator]-(spacer)-BN(2-14)-NH(2), where M: (99m)Tc or (185/187)Re, chelator: Gly-Gly-Cys-, spacer: -(arginine)(3)-, M-BN-A; spacer: -(ornithine)(3)-, M-BN-O; have been prepared and evaluated as tumor imaging agents.
  
  
  RESULTS
  The peptides under study presented high radiolabelling efficiency (>98%), significant stability in human plasma (>60% intact radiolabelled peptide after 1h incubation) and comparable receptor binding affinity with the standard [(125)I-Tyr(4)]-BN. Their internalization rates in the prostate cancer PC-3 cells differed, although the amount of internalized peptide was the same. The biodistribution and the dynamic γ-camera imaging studies in normal and PC-3 tumor-bearing SCID mice have shown significant tumor uptake, combined with fast blood clearance, through the urinary pathway.
  
  
  CONCLUSIONS
  The addition of the charged aa spacer in the BN structure was advantageous for biodistribution, pharmacokinetics and tumor targeting ability, because it reduced the upper abdominal radioactivity levels and increased tumor/normal tissue contrast ratios.
authors.affiliation: Institute of Radioisotopes & Radiodiagnostic Products, NCSR Demokritos, 15310 Athens, Greece. xliolios@upatras.gr
authors.forename: Christos C
authors.initials: CC
authors.lastname: Liolios
authors.forename: Eirini A
authors.initials: EA
authors.lastname: Fragogeorgi
authors.forename: Christos
authors.initials: C
authors.lastname: Zikos
authors.forename: George
authors.initials: G
authors.lastname: Loudos
authors.forename: Stavros
authors.initials: S
authors.lastname: Xanthopoulos
authors.forename: Penelope
authors.initials: P
authors.lastname: Bouziotis
authors.forename: Maria
authors.initials: M
authors.lastname: Paravatou-Petsotas
authors.forename: Evangelia
authors.initials: E
authors.lastname: Livaniou
authors.forename: Alexandra D
authors.initials: AD
authors.lastname: Varvarigou
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Sivolapenko
mesh_terms: D000818:Animals; D001692:Biological Transport; D001839:Bombesin / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010455:Peptides / Q000097:blood / Q000493:pharmacokinetics*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D055550:Protein Stability; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics*; D018004:Receptors, Bombesin / Q000378:metabolism; D013667:Technetium / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014741:Video Recording
chemical_list: D008024:Ligands; D010455:Peptides; D019275:Radiopharmaceuticals; D018004:Receptors, Bombesin; D013667:Technetium; D001839:Bombesin