title: Radiolabeling and biological evaluation of the GX1 and RGD-GX1 peptide sequence for angiogenesis targeting.
abstract: BACKGROUND
  Aiming to develop a novel (99m)Tc-labeled imaging agent, for angiogenesis and tumor receptors, two peptides obtained from phage display library, namely GX1 and the heterodimer RGD-GX1, were synthesized in a cyclic conformation. They were radiolabeled with (99m)Tc, employing the HYNIC chelator, for radiochemical evaluation and biological properties.
  
  
  METHODS
  Radiolabeling, radiochemical control, plasma protein binding, and partition coefficient were assessed for both radioconjugates. Biodistribution in healthy Balb/c mice was carried out, in order to evaluate the biological behaviour of the radiocomplexes.
  
  
  RESULTS
  The conjugates displayed a rather similar pharmacokinetic profile. They were prepared with high radiochemical purity (>96%), and both were hydrophilic (log P of -2.25 and -2.51 respectively). Preferential renal excretion was observed. Kidney uptake (42.31±5.35 %ID/g) for (99m)Tc-HYNIC-E-[c(RGDfk)-c(GX1)], 1h post-injection was about three times higher than the uptake of (99m)Tc-HYNIC-PEG4-c(GX1) (11.92±4.77%ID/g). Total blood, bone and muscle values revealed a slightly slower clearance for the RGD-GX1 radiocomplex.
  
  
  CONCLUSIONS
  The high radiochemical purity achieved, and the similar in vivo profile observed for both radioconjugates, make them potential candidates for radiopharmaceuticals for tumor imaging. Further investigations of binding affinity, and uptake of GX1 and RGD-GX1 peptides in tumor models, are warranted.
authors.affiliation: Radiopharmacy, Institute of Energy and Nuclear Research, Sao Paulo, SP, Brazil, Av. Prof. Lineu Prestes, 2242 05508-000 São Paulo, SP, Brazil. Electronic address: ericaoliveira@usp.br.
authors.forename: E A
authors.initials: EA
authors.lastname: Oliveira
authors.affiliation: Radiopharmacy, Institute of Energy and Nuclear Research, Sao Paulo, SP, Brazil, Av. Prof. Lineu Prestes, 2242 05508-000 São Paulo, SP, Brazil.
authors.forename: B L
authors.initials: BL
authors.lastname: Faintuch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002614:Chelating Agents / Q000737:chemistry; D019281:Dimerization; D004355:Drug Stability; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D009539:Nicotinic Acids / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D011854:Radiochemistry; D013667:Technetium; D014018:Tissue Distribution
chemical_list: C120392:6-hydrazinopyridine-3-carboxylic acid; D001798:Blood Proteins; D002614:Chelating Agents; D006834:Hydrazines; D009539:Nicotinic Acids; D009842:Oligopeptides; D013667:Technetium; C047981:arginyl-glycyl-aspartic acid
keywords: Angiogenesis; RGD and GX1 peptides; Technetium-99m