Synthesis, biodistribution and excretion of radiolabeled poly(2-alkyl-2-oxazoline)s

J Control Release. 2007 Jun 22;119(3):291-300. doi: 10.1016/j.jconrel.2007.02.015. Epub 2007 Mar 2.

Abstract

Here we report on the preparation of well defined water-soluble poly(2-methyl-2-oxazoline) and poly(2-ethyl-2-oxazoline) terminally equipped with a chelator (N,N',N'',N'''-tetraazacylododecane-1,4,7,10-tetraacetic acid (DOTA)) for radionuclide labeling. The tissue distribution and excretion of (111)In-labeled poly(2-alkyl-2-oxazoline)s were studied in mice. We found that the hydrophilic polymers do not accumulate in tissues and are rapidly cleared from the blood pool, predominantly by glomerular filtration in the kidneys. In contrast only a small fraction is excreted via the hepatobiliary tract. Only minimal amounts of poly(2-alkyl-2-oxazoline)s are taken up by the reticuloendothelial system (RES). Scintigraphic studies revealed the feasibility of in vivo imaging of (111)In-labeled poly(2-oxazoline)s. Since additional functionalities for targeting can readily be introduced into poly(2-oxazoline)s via functional monomer units, these compounds fulfill fundamental requirements for an application as carrier molecules in radionuclide therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Biological Availability
  • Chitin / analogs & derivatives*
  • Chitin / chemical synthesis
  • Chitin / chemistry
  • Chitin / pharmacokinetics
  • Drug Carriers* / chemical synthesis
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacokinetics
  • Female
  • Heterocyclic Compounds, 1-Ring / chemistry*
  • Indium Radioisotopes / chemistry
  • Indium Radioisotopes / pharmacokinetics*
  • Indium Radioisotopes / therapeutic use
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred Strains
  • Oxazoles* / chemical synthesis
  • Oxazoles* / chemistry
  • Oxazoles* / pharmacokinetics
  • Polyamines
  • Polymers* / chemical synthesis
  • Polymers* / chemistry
  • Polymers* / pharmacokinetics
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Solubility
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Heterocyclic Compounds, 1-Ring
  • Indium Radioisotopes
  • Oxazoles
  • Polyamines
  • Polymers
  • Radiopharmaceuticals
  • poly(2-ethyl-2-oxazoline)
  • poly(2-methyl-2-oxazoline)
  • Chitin
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid