title: Neovascularization after ischemic injury: evaluation with ⁹⁹(m)Tc-HYNIC-RGD.
abstract: OBJECTIVE
  Angiogenesis involves many mediators including integrins, and the tripeptide RGD is a target amino acid recognition sequence for many of them. Hindlimb ischemia is a simple and convenient animal model however standardization of the injection procedures in the devascularized and control limb is lacking, thus rendering difficult the interpretation of results. The aim of this investigations was to evaluate neovascularization in a hindlimb murine model by means of ⁹⁹(m)Tc-HYNIC-ß-Ala-RGD.
  
  
  METHODS
  ⁹⁹(m)Tc-HYNIC-RGD analog was prepared using coligands. Ischemia was induced in Wistar rats by double- ligation of the common femoral artery. Radiolabeled RGD was injected after 2h, as well as 1, 3, 5, 7, 10 and 14 days. Uptake was evaluated by planar imaging and biodistribution studies.
  
  
  RESULTS
  The highest ratio between ischemia and control was achieved at the 7th day (2.62 ± 0.95), with substantial decrease by the 14th day. For pertechnetate the 7th day ratio was 0.87 ± 0.23. Scintigraphic image confirmed different uptakes.
  
  
  CONCLUSIONS
  ⁹⁹(m)Tc-HYNIC-RGD analog concentrated in ischemic tissue by the time of widespread angiogenesis and pertechnetate confirmed reduction in blood flow. In this sense, the protocol can be recommended for ischemic models.
authors.affiliation: Radiopharmacy Center, IPEN, University of Sao Paulo, SP, Brazil. blfaintuch@hotmail.com
authors.forename: Bluma Linkowski
authors.initials: BL
authors.lastname: Faintuch
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Teodoro
authors.forename: Erica Aparecida de
authors.initials: EA
authors.lastname: Oliveira
authors.forename: Eutimio Gustavo Fernández
authors.initials: EG
authors.lastname: Nuñez
authors.forename: Joel
authors.initials: J
authors.lastname: Faintuch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D006614:Hindlimb / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism; D007511:Ischemia / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009842:Oligopeptides; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D009842:Oligopeptides; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C561218:technetium 99m HYNIC-beta-Ala-RGD; C047981:arginyl-glycyl-aspartic acid