title: Targeted radionuclide therapy with RAFT-RGD radiolabelled with (90)Y or (177)Lu in a mouse model of αvβ3-expressing tumours.
abstract: OBJECTIVE
  The αvβ3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets the αvβ3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with β(-) emitters in a nude mouse model of αvβ3 integrin-expressing tumours.
  
  
  METHODS
  Biodistribution and SPECT/CT imaging studies were performed after injection of (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvβ3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD and (90)Y-RAFT-RAD or (177)Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvβ3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvβ3. Tumour volume doubling time was used to evaluate the efficacy of each treatment.
  
  
  RESULTS
  Injection of 37 MBq of (90)Y-RAFT-RGD into mice with large αvβ3-positive tumours or 37 MBq of (177)Lu-RAFT-RGD into mice with small αvβ3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of (90)Y-RAFT-RAD or 37 MBq of (177)Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of (90)Y-RAFT-RGD had no effect on the growth of αvβ3-negative tumours.
  
  
  CONCLUSIONS
  (90)Y-RAFT-RGD and (177)Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy.
authors.affiliation: INSERM, U1039, Grenoble, 38000, France.
authors.forename: A
authors.initials: A
authors.lastname: Bozon-Petitprin
authors.forename: S
authors.initials: S
authors.lastname: Bacot
authors.forename: A S
authors.initials: AS
authors.lastname: Gauchez
authors.forename: M
authors.initials: M
authors.lastname: Ahmadi
authors.forename: J C
authors.initials: JC
authors.lastname: Bourre
authors.forename: D
authors.initials: D
authors.lastname: Marti-Batlle
authors.forename: P
authors.initials: P
authors.lastname: Perret
authors.forename: A
authors.initials: A
authors.lastname: Broisat
authors.forename: L M
authors.initials: LM
authors.lastname: Riou
authors.forename: M
authors.initials: M
authors.lastname: Claron
authors.forename: D
authors.initials: D
authors.lastname: Boturyn
authors.forename: D
authors.initials: D
authors.lastname: Fagret
authors.forename: Catherine
authors.initials: C
authors.lastname: Ghezzi
authors.forename: J P
authors.initials: JP
authors.lastname: Vuillez
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D008187:Lutetium / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics / Q000532:radiotherapy; D010456:Peptides, Cyclic / Q000009:adverse effects / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; C574552:RAFT-RGD; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D008187:Lutetium