title: 18F-labeled bombesin analog for specific and effective targeting of prostate tumors expressing gastrin-releasing peptide receptors.
abstract: Bombesin is a peptide exhibiting high affinity for the gastrin-releasing peptide receptor (GRPr), which is highly overexpressed on prostate cancer cells. In the present study, we developed an (18)F-labeled bombesin analog, (18)F-BAY 86-4367, which is currently being clinically tested for use in PET of prostate cancer.
  
  
  METHODS
  In vitro pharmacologic studies were performed to characterize the nonradioactive ((19)F) standard of the bombesin analog for binding affinity and selectivity for GRPr. The stability of (18)F-BAY 86-4367 was determined in murine and human plasma. In vivo, the tumor-targeting potential and pharmacokinetic profile of the (18)F tracer were analyzed with biodistribution experiments and PET studies of prostate tumor-bearing mice.
  
  
  RESULTS
  The nonradioactive ((19)F) standard of the bombesin analog showed subnanomolar and GRPr-selective binding affinity. The stability of the tracer in murine and human plasma was found to be high. In 2 prostate cancer xenograft models (PC-3 and LNCaP), (18)F-BAY 86-4367 showed more specific and effective GRPr-based targeting in vivo than the benchmark radiotracers (18)F-fluoroethylcholine and (18)F-FDG. In addition, rapid tumor targeting and fast renal excretion (∼70%) and hepatobiliary excretion (∼10%) were identified in both xenograft models. Furthermore, PET studies provided clear and specific visualization of PC-3 tumors in mice.
  
  
  CONCLUSIONS
  Favorable preclinical data showing specific and effective tumor targeting by (18)F-BAY 86-4367 suggest that a clinical trial be undertaken to test its diagnostic utility in PET for prostate carcinoma patients.
authors.affiliation: Department of Chemistry and Applied Biosciences, Center for Radiopharmaceutical Sciences of ETH, PSI, and USZ, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Honer
authors.forename: Linjing
authors.initials: L
authors.lastname: Mu
authors.forename: Timo
authors.initials: T
authors.lastname: Stellfeld
authors.forename: Keith
authors.initials: K
authors.lastname: Graham
authors.forename: Miljen
authors.initials: M
authors.lastname: Martic
authors.forename: Cindy R
authors.initials: CR
authors.lastname: Fischer
authors.forename: Lutz
authors.initials: L
authors.lastname: Lehmann
authors.forename: Pius A
authors.initials: PA
authors.lastname: Schubiger
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
authors.forename: Ludger
authors.initials: L
authors.lastname: Dinkelborg
authors.forename: Ananth
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Sandra
authors.initials: S
authors.lastname: Borkowski
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001839:Bombesin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D002460:Cell Line; D003544:Cysteic Acid / Q000737:chemistry; D004355:Drug Stability; D005462:Fluorine Radioisotopes; D006801:Humans; D007202:Indicators and Reagents; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D018004:Receptors, Bombesin / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C556307:BAY 86-4367; D005462:Fluorine Radioisotopes; D007202:Indicators and Reagents; D019275:Radiopharmaceuticals; D018004:Receptors, Bombesin; D003544:Cysteic Acid; D001839:Bombesin