Synthesis and in vitro cellular uptake of 11C-labeled 5-aminolevulinic acid derivative to estimate the induced cellular accumulation of protoporphyrin IX

Bioorg Med Chem Lett. 2013 Aug 15;23(16):4567-70. doi: 10.1016/j.bmcl.2013.06.025. Epub 2013 Jun 20.

Abstract

Protoporphyrin IX (PpIX) accumulation induced by exogenous 5-aminolevulinic acid (ALA) in tumors affects the therapeutic efficacy of ALA-based photodynamic and sonodynamic therapies. To develop a new imaging probe to estimate the ALA-induced PpIX accumulation, (11)C-labeled ALA analog (4), an ALA-dehydratase inhibitor, was radiosynthesized via (11)C-methylation of a Schiff-base-activated precursor in the presence of tetrabutylammonium fluoride, followed by the hydrolysis of ester and imine groups. The cellular uptake of 4 linearly increased with time and was inhibited by ALA and other transporter competitors. Monitoring analog 4 with positron emission tomography might be useful to estimate the ALA-induced PpIX accumulation in tumors.

Keywords: 5-Aminolevulinic acid (ALA); Photodynamic therapy (PDT); Positron emission tomography (PET); Radiosynthesis; Sonodynamic therapy (SDT).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminolevulinic Acid / chemical synthesis
  • Aminolevulinic Acid / chemistry
  • Aminolevulinic Acid / pharmacokinetics*
  • Binding, Competitive
  • Carbon Radioisotopes / metabolism
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Humans
  • Molecular Structure
  • Neoplasms / chemistry*
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacokinetics
  • Positron-Emission Tomography
  • Protoporphyrins / analysis
  • Protoporphyrins / metabolism*
  • Time Factors

Substances

  • Carbon Radioisotopes
  • Photosensitizing Agents
  • Protoporphyrins
  • Aminolevulinic Acid
  • protoporphyrin IX