title: Radiolabeled RGD tracer kinetics annotates differential αvβ 3 integrin expression linked to cell intrinsic and vessel expression.
abstract: OBJECTIVE
  The purpose of this paper is to study the association between RGD binding kinetics and αvβ3 integrin receptor density in the complex tumor milieu.
  
  
  METHODS
  We assessed αvβ3 in vitro and by (68)Ga-DOTA-[c(RGDfK)]2 positron emission tomography (PET) in tumors with varying αvβ3.
  
  
  RESULTS
  Intrinsic αvβ3 expression decreased in the order of M21 >>> MDA-MB-231 > M21L in cells. Tumor volume of distribution by PET, V T, was significantly higher in M21 compared to isogenic M21L tumors (0.40 ± 0.01 versus 0.25 ± 0.02; p < 0.01) despite similar microvessel density (MVD) likely due to higher αvβ3. V T for MDA-MB-231 (0.40 ± 0.04) was comparable to M21 despite lower αvβ3 but in keeping with the higher MVD, suggesting superior tracer distribution.
  
  
  CONCLUSIONS
  This study demonstrates that radioligand binding kinetics of PET data can be used to discriminate tumors with different αvβ3 integrin expression-a key component of the angiogenesis phenotype-in vivo.
authors: Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, London, W12 0NN, UK.
authors: Israt S
authors: IS
authors: Alam
authors: Timothy H
authors: TH
authors: Witney
authors: Giampaolo
authors: G
authors: Tomasi
authors: Laurence
authors: L
authors: Carroll
authors: Frazer J
authors: FJ
authors: Twyman
authors: Quang-Dé
authors: QD
authors: Nguyen
authors: Eric O
authors: EO
authors: Aboagye
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D007700:Kinetics; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D009942:Organometallic Compounds; D010456:Peptides, Cyclic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers
chemical_list: C532505:68Ga-DOTA-cyclo(arginyl-glycyl-aspartyl-phenylalanyl-lysyl); D039302:Integrin alphaVbeta3; D009942:Organometallic Compounds; D010456:Peptides, Cyclic; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011849:Radioactive Tracers