PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice

PLoS One. 2015 Jul 1;10(7):e0129310. doi: 10.1371/journal.pone.0129310. eCollection 2015.

Abstract

64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model was used for the investigations, and it was found that the approximately 13 nm nanodiscs, due to their size, permeate deeply into cancer tissue. This makes them promising candidates for both drug delivery purposes and as advanced imaging agents. For the radiolabelling, a simple approach for 64Cu radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Copper Radioisotopes*
  • Disease Models, Animal
  • Heterocyclic Compounds, 1-Ring
  • Heterografts
  • Humans
  • Mice
  • Nanostructures* / chemistry
  • Neoplasms / diagnosis*
  • Particle Size
  • Phosphatidylcholines
  • Positron-Emission Tomography* / methods
  • Radiopharmaceuticals*
  • Tissue Distribution
  • Tomography, X-Ray Computed* / methods

Substances

  • Copper Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Phosphatidylcholines
  • Radiopharmaceuticals
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • 1-palmitoyl-2-oleoylphosphatidylcholine

Grants and funding

This work was supported by the University of Copenhagen and Danish Ministry of Science, Innovation and Higher Education. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.