title: Novel series of (177)Lu-labeled bombesin derivatives with amino acidic spacers for selective targeting of human PC-3 prostate tumor cells.
abstract: OBJECTIVE
  Bombesin (BBN) has demonstrated the ability to bind with high affinity and specificity to GRP receptor, overexpressed on human prostate cancer. A large number of BBN derivatives have been synthesized for this purpose but most of them exhibit high abdominal accumulation, which may represent a problem in their clinical use due to serious side effects to patients. In this study we describe the results of radiolabeling with lutetium-177, stability and in vivo studies of novel phenyl-glycine-extended bombesin derivatives. The spacers were inserted to improve bombesin in vivo properties and to reduce its target to non-tumor sites.
  
  
  METHODS
  Preliminary studies were done to establish the ideal conditions for labeling bombesin derivatives. Chromatography systems were applied to determine free lutetium and the stability of the preparations was evaluated either after storing at 2-8 ºC or incubation in human serum at 37 ºC. In vivo experiments included biodistribution, pharmacokinetics and SPECT images and were performed in Balb-c and Nude mice bearing PC-3 xenografts.
  
  
  RESULTS
  The derivatives were labeled with high yield and kept stable at 2-8 ºC and are metabolized by human serum enzymes. In vivo studies showed fast blood clearance of labeled peptides and rapid excretion, performed mainly by renal pathway. In addition, biodistribution and imaging studies showed low abdominal accumulation and significant and specific tumor uptake of (177)Lu-labeled derivatives.
  
  
  CONCLUSIONS
  The derivative with longer spacer holds a higher potential as radiopharmaceutical for prostate tumor diagnosis and the derivatives with shorter spacers are potential radiopharmaceuticals for prostate tumor treatment.
authors.affiliation: Radiopharmacy Directory, Nuclear and Energy Research Institute (IPEN/CNEN), São Paulo, Brazil. priscillapujatti@yahoo.com.br
authors.forename: P B
authors.initials: PB
authors.lastname: Pujatti
authors.forename: J S
authors.initials: JS
authors.lastname: Santos
authors.forename: R M
authors.initials: RM
authors.lastname: Couto
authors.forename: L T U H
authors.initials: LT
authors.lastname: Melero
authors.forename: M F
authors.initials: MF
authors.lastname: Suzuki
authors.forename: C R J
authors.initials: CR
authors.lastname: Soares
authors.forename: S R M
authors.initials: SR
authors.lastname: Grallert
authors.forename: J
authors.initials: J
authors.lastname: Mengatti
authors.forename: E B
authors.initials: EB
authors.lastname: De Araújo
mesh_terms: D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004355:Drug Stability; D006801:Humans; D008187:Lutetium / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging*; D011868:Radioisotopes / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon; D014183:Transplantation, Heterologous
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium; D001839:Bombesin