title: Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP(®) Peptides) Conjugated with Different Fluorescent Dyes.
abstract: Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP(®) peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors.
  
  
  
  Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP(®) variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP(®) variants in multidimensional space of spectral parameters.
  
  
  
  The fluorescently labeled pHLIP(®) variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP(®) peptide.
  
  
  
  Different cargo molecules conjugated with pHLIP(®) peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP(®)-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions.
authors.affiliation: Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI, 02881, USA.
authors.forename: Ramona-Cosmina
authors.initials: RC
authors.lastname: Adochite
authors.affiliation: Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI, 02881, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Moshnikova
authors.affiliation: Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI, 02881, USA.
authors.forename: Jovana
authors.initials: J
authors.lastname: Golijanin
authors.affiliation: Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI, 02881, USA.
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Andreev
authors.affiliation: Department of Computer Sciences and Statistics, University of Rhode Island, 9 Greenhouse Road, Kingston, RI, 02881, USA.
authors.forename: Natallia V
authors.initials: NV
authors.lastname: Katenka
authors.affiliation: Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI, 02881, USA. reshetnyak@uri.edu.
authors.forename: Yana K
authors.initials: YK
authors.lastname: Reshetnyak
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000737:chemistry; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D015999:Multivariate Analysis; D010455:Peptides / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D010455:Peptides
keywords: Fluorescent-guided surgery; Imaging; Targeting of submillimeter metastatic lesions; Tumor acidity