In vivo biodistribution of calcium phosphate nanoparticles after intravascular, intramuscular, intratumoral, and soft tissue administration in mice investigated by small animal PET/CT

Acta Biomater. 2020 Jun;109:244-253. doi: 10.1016/j.actbio.2020.03.031. Epub 2020 Apr 4.

Abstract

Calcium phosphate nanoparticles were covalently surface-functionalized with the ligand DOTA and loaded with the radioisotope 68Ga. The biodistribution of such 68Ga-labelled nanoparticles was followed in vivo in mice by positron emission tomography in combination with computer tomography (PET-CT). The biodistribution of 68Ga-labelled nanoparticles was compared for different application routes: intravenous, intramuscular, intratumoral, and into soft tissue. The particle distribution was measured in vivo by PET-CT after 5 min, 15 min, 30 min, 1 h, 2 h, and 4 h, and ex vivo after 5 h. After intravenous injection (tail vein), the nanoparticles rapidly entered the lungs with later redistribution into liver and spleen. The nanoparticles remained mostly at the injection site following intramuscular, intratumoral, or soft tissue application, with less than 10 percent being mobilized into the blood stream. STATEMENT OF SIGNIFICANCE: The in vivo biodistribution of DOTA-terminated calcium phosphate nanoparticles was followed by PET/CT. To our knowledge, this is the first study of this kind. Four different application routes of clinical relevance were pursued: Intravascular, intramuscular, intratumoral, and into soft tissue. Given the high importance of calcium phosphate as biomaterial and for nanoparticular drug delivery and immunization, this is most important to assess the biofate of calcium phosphate nanoparticles for therapeutic application and also judge biodistribution of nanoscopic calcium phosphate ceramics, including debris from endoprostheses and related implants.

Keywords: Biodistribution; Calcium phosphate; Computer tomography; Imaging; Nanoparticles; Positron-emission tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Phosphates / administration & dosage
  • Calcium Phosphates / chemistry
  • Calcium Phosphates / pharmacokinetics*
  • Cell Line, Tumor
  • Gallium Radioisotopes / administration & dosage
  • Gallium Radioisotopes / chemistry
  • Gallium Radioisotopes / pharmacokinetics
  • Heterocyclic Compounds, 1-Ring / administration & dosage
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics
  • Humans
  • Injections, Intramuscular
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Neoplasms / diagnostic imaging
  • Neoplasms / metabolism*
  • Positron Emission Tomography Computed Tomography

Substances

  • Calcium Phosphates
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • calcium phosphate
  • Gallium-68