title: Measuring tumor aggressiveness and targeting metastatic lesions with fluorescent pHLIP.
abstract: OBJECTIVE
  Malignant cancer foci develop acidic extracellular environments. Mild acidic conditions trigger insertion and folding of the pH (low) insertion peptide (pHLIP(TM)) across a cellular membrane, enabling targeting of such lesions.
  
  
  METHODS
  We employed optical imaging to follow targeting by fluorescent pHLIP given i.v. in mice. For visualization, Cy5.5 and Alexa750 were covalently attached to the N terminus of pHLIP, which stays outside of a cell membrane after transmembrane insertion.
  
  
  RESULTS
  We demonstrate that pHLIP targets: (a) tumors of different origins established by subcutaneous injection of cancer cells, (b) spontaneous prostate tumors in TRAMP mice and (c) metastatic lesions in lung pHLIP accumulation in tumors correlates with tumor aggressiveness. Within a tumor, it stains extracellular spaces and cellular membranes.
  
  
  CONCLUSIONS
  Tissue acidity can be detected by pHLIP peptide insertion and used to diagnose primary tumors, metastatic lesions, and lipid bodies in necrotic tissues. The ability of pHLIP to differentially bind metastatic and non-metastatic tumors may provide a new approach for evaluating cancer prognosis.
authors.affiliation: Physics Department, University of Rhode Island, Kingston, RI 02881, USA.
authors.forename: Yana K
authors.initials: YK
authors.lastname: Reshetnyak
authors.forename: Lan
authors.initials: L
authors.lastname: Yao
authors.forename: Sida
authors.initials: S
authors.lastname: Zheng
authors.forename: Sergey
authors.initials: S
authors.lastname: Kuznetsov
authors.forename: Donald M
authors.initials: DM
authors.lastname: Engelman
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Andreev
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005453:Fluorescence; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007267:Injections; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D009361:Neoplasm Invasiveness / Q000175:diagnosis* / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000175:diagnosis* / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*; D013194:Staining and Labeling; D013388:Succinimides; D051598:Whole Body Imaging
chemical_list: C502599:Alexa Fluor 750; D008565:Membrane Proteins; D013388:Succinimides; C533201:pHLIP protein; D005947:Glucose