title: In-vivo detection of the erythropoietin receptor in tumours using positron emission tomography.
abstract: OBJECTIVE
  Recombinant human erythropoietin (rhuEpo) is used clinically to treat anaemia. However, rhuEpo-treated cancer patients show decreased survival rates and erythropoietin receptor (EpoR) expression has been found in patient tumour tissue. Thus, rhuEpo application might promote EpoR(+) tumour progression. We therefore developed the positron emission tomography (PET)-probe (68)Ga-DOTA-rhuEpo and evaluated its performance in EpoR(+) A549 non-small-cell lung cancer (NSCLC) xenografts.
  
  
  METHODS
  (68)Ga-DOTA-rhuEpo was generated by coupling DOTA-hydrazide to carbohydrate side-chains of rhuEpo. Biodistribution was determined in tumour-bearing mice 0.5, 3, 6, and 9 h after probe injection. Competition experiments were performed by co-injecting (68)Ga-DOTA-rhuEpo and rhuEpo in five-fold excess. Probe specificity was further evaluated histologically using Epo-Cy5.5 stainings.
  
  
  RESULTS
  The blood half-life of (68)Ga-DOTA-rhuEpo was 2.6 h and the unbound fraction was cleared by the liver and kidney. After 6 h, the highest tumour to muscle ratio was reached. The highest (68)Ga-DOTA-rhuEpo accumulation was found in liver (10.06 ± 6.26%ID/ml), followed by bone marrow (1.87 ± 0.53%ID/ml), kidney (1.58 ± 0.39%ID/ml), and tumour (0.99 ± 0.16%ID/ml). EpoR presence in these organs was histologically confirmed. Competition experiments showed significantly (p < 0.05) lower PET-signals in tumour and bone marrow at 3 and 6 h.
  
  
  CONCLUSIONS
  (68)Ga-DOTA-rhuEpo shows favourable pharmacokinetic properties and detects EpoR specifically. Therefore, it might become a valuable radiotracer to monitor EpoR status in tumours and support decision-making in anaemia therapy.
  
  
  CONCLUSIONS
  • PET-probe (68) Ga-DOTA-rhuEpo was administered to assess the EpoR status in vivo • (68) Ga-DOTA-rhuEpo binds specifically to EpoR positive organs in vivo • Tumour EpoR status determination might enable decision-making in anaemia therapy with rhuEpo.
authors.affiliation: Department for Experimental Molecular Imaging (ExMI), Medical Faculty, RWTH Aachen University, Pauwelsstraße 20, 52074, Aachen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Fuge
authors.forename: Dennis
authors.initials: D
authors.lastname: Doleschel
authors.forename: Anne
authors.initials: A
authors.lastname: Rix
authors.forename: Felix
authors.initials: F
authors.lastname: Gremse
authors.forename: Axel
authors.initials: A
authors.lastname: Wessner
authors.forename: Oliver
authors.initials: O
authors.lastname: Winz
authors.forename: Felix
authors.initials: F
authors.lastname: Mottaghy
authors.forename: Wiltrud
authors.initials: W
authors.lastname: Lederle
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000000981:diagnostic imaging; D045744:Cell Line, Tumor; D000068817:Epoetin Alfa; D004921:Erythropoietin; D005260:Female; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry* / Q000000981:diagnostic imaging; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms; D009374:Neoplasms, Experimental / Q000737:chemistry* / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D011994:Recombinant Proteins; D014018:Tissue Distribution
chemical_list: D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa