Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP(®) Peptides) Conjugated with Different Fluorescent Dyes

Mol Imaging Biol. 2016 Oct;18(5):686-96. doi: 10.1007/s11307-016-0949-6.

Abstract

Purpose: 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.

Procedures: 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.

Results: 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.

Conclusions: 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.

Keywords: Fluorescent-guided surgery; Imaging; Targeting of submillimeter metastatic lesions; Tumor acidity.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Contrast Media / chemistry
  • Female
  • Fluorescent Dyes / metabolism*
  • Hydrogen-Ion Concentration
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / secondary
  • Mammary Neoplasms, Animal / pathology*
  • Mice, Inbred BALB C
  • Molecular Weight
  • Multivariate Analysis
  • Peptides / metabolism*
  • Time Factors
  • Tissue Distribution

Substances

  • Contrast Media
  • Fluorescent Dyes
  • Peptides