title: Dual in vivo quantification of integrin-targeted and protease-activated agents in cancer using fluorescence molecular tomography (FMT).
abstract: OBJECTIVE
  Integrins, especially α(v)β(3) and α(v)β(5), are upregulated in tumor cells and activated endothelial cells and as such, serve as cancer biomarkers. We developed a novel near-infrared-labeled optical agent for the in vivo detection and quantification of α(v)β(3)/α(v)β(5).
  
  
  METHODS
  A small peptidomimetic α(v)β(3) antagonist was synthesized, coupled to a near-infrared fluorescent (NIRF) dye, and tested for binding specificity using integrin-overexpressing cells, inhibition of vitronectin-mediated cell attachment, binding to tumor and endothelial cells in vitro, and competition studies. Pharmacokinetics, biodistribution, specificity of tumor targeting, and the effect of an antiangiogenic treatment were assessed in vivo.
  
  
  RESULTS
  The integrin NIRF agent showed strong selectivity towards α(v)β(3/)α(v)β(5) in vitro and predominant tumor distribution in vivo, allowing noninvasive and real-time quantification of integrin signal in tumors. Antiangiogenic treatment significantly inhibited integrin signal in vivo but had no effect on a cathepsin-cleavable NIR agent. Simultaneous imaging revealed different patterns of distribution reflecting the underlying differences in integrin and cathepsin biology during tumor progression.
  
  
  CONCLUSIONS
  NIRF-labeled integrin antagonists allow noninvasive molecular fluorescent imaging and quantification of tumors in vivo, improving and providing more refined approaches for cancer detection and treatment monitoring.
authors: VisEn Medical, Bedford, MA, USA. skossodo@visenmedical.com
authors: Sylvie
authors: S
authors: Kossodo
authors: Maureen
authors: M
authors: Pickarski
authors: Shu-An
authors: SA
authors: Lin
authors: Alexa
authors: A
authors: Gleason
authors: Renee
authors: R
authors: Gaspar
authors: Chiara
authors: C
authors: Buono
authors: Guojie
authors: G
authors: Ho
authors: Agnieszka
authors: A
authors: Blusztajn
authors: Garry
authors: G
authors: Cuneo
authors: Jun
authors: J
authors: Zhang
authors: Jayme
authors: J
authors: Jensen
authors: Richard
authors: R
authors: Hargreaves
authors: Paul
authors: P
authors: Coleman
authors: George
authors: G
authors: Hartman
authors: Milind
authors: M
authors: Rajopadhye
authors: Le Thi
authors: LT
authors: Duong
authors: Cyrille
authors: C
authors: Sur
authors: Wael
authors: W
authors: Yared
authors: Jeffrey
authors: J
authors: Peterson
authors: Bohumil
authors: B
authors: Bednar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D005453:Fluorescence; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D010447:Peptide Hydrolases / Q000378:metabolism*; D014018:Tissue Distribution; D014054:Tomography / Q000379:methods*; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D016023:Integrins; D010447:Peptide Hydrolases