title: Radiolabeled nano-peptides show specificity for an animal model of human PC3 prostate cancer cells.
abstract: OBJECTIVE
  Cancer has been investigated using various pre-targeting techniques or models focusing on radiobombesin analogues; however, both are not offered together. In this study, nano-bombesin labeling by a pre-targeting system was undertaken to develop an alternative approach for prostate tumor treatment.
  
  
  METHODS
  A two-step pre-targeting system utilizing a combination of streptavidin (SA), biotinylated morpholino (B-MORF), biotinylated BBN (B-BBN) with two different spacers (b-Ala and PEG), and a radiolabeled cMORF was evaluated in vitro and in vivo.
  
  
  RESULTS
  Final conjugation conditions consisted of a 1:1:2 ratio of SA:B-MORF:B-BBN, followed by addition of 99mTc-cMORF to compensate for free MORF. In vitro binding experiments with prostate cancer cells (PC-3) revealed that total binding was time-dependent for the Ala spacer but not for the PEG spacer. The highest accumulation (5.06 ± 1.98 %) was achieved with 1 hour of incubation, decreasing as time progressed. Specific binding fell to 1.05 ± 0.35 %. The pre-targeting biodistribution in healthy Swiss mice was measured at different time points, with the best responses observed for 7-h and 15-h incubations. The effector, 99mTc-MAG3-cMORF, was administered 2 h later. Strong kidney excretion was always documented. The greatest tumor uptake was 2.58 ± 0.59 %ID/g at 7 h for B-bAla-BBN, with a region of interest (ROI) value of 3.9 % during imaging. The tumor/blood ratio was low due to the slow blood clearance; however, the tumor/muscle ratio was 5.95.
  
  
  CONCLUSIONS
  The pre-targeting approach with a peptide was a viable concept. Further evaluation with modified sequences of MORF, including less cytosine, and additional test intervals could be worthwhile.
authors.affiliation: Centro de Radiofarmácia, Instituto de Pesquisas Energéticas e Nucleares, São Paulo, Brazil.
authors.forename: Bluma Linkowski
authors.initials: BL
authors.lastname: Faintuch
authors.forename: Gustavo Eutimio Fernandez
authors.initials: GE
authors.lastname: Núñez
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Teodoro
authors.forename: Ana M
authors.initials: AM
authors.lastname: Moro
authors.forename: Jair
authors.initials: J
authors.lastname: Mengatti
mesh_terms: D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000378:metabolism*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D009025:Morpholines / Q000493:pharmacokinetics*; D053758:Nanoparticles; D015609:Organotechnetium Compounds; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D011868:Radioisotopes / Q000737:chemistry; D011877:Radionuclide Imaging; D011897:Random Allocation; D019809:Streptavidin / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D009025:Morpholines; D015609:Organotechnetium Compounds; D011868:Radioisotopes; C531054:technetium 99m HYNIC-bombesin; D019809:Streptavidin; D001839:Bombesin