Positron Emission Tomography Based Analysis of Long-Circulating Cross-Linked Triblock Polymeric Micelles in a U87MG Mouse Xenograft Model and Comparison of DOTA and CB-TE2A as Chelators of Copper-64

Andreas I Jensen, Tina Binderup, Pramod Kumar EK, Andreas Kjær, Palle H Rasmussen, Thomas L Andresen

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31 Citationer (Scopus)

Abstract

Copolymers of ABC-type (PEG-PHEMA-PCMA) architecture were prepared by atom transfer radical polymerization and formulated as micelles with functionalizable primary alcohols in the shell-region (PHEMA-block) to which the metal-ion chelators DOTA or CB-TE2A were conjugated. Using this micelle system we compared the in vivo stabilities of DOTA and CB-TE2A as chelators of (64)Cu in micelle nanoparticles. The coumarin polymer (PCMA-block) micelle core was cross-linked by UV irradiation at 2 W/cm(2) for 30 min. The cross-linked micelles were labeled with (64)Cu at room temperature for 2 h (DOTA) or 80 °C for 3 h (CB-TE2A), giving labeling efficiencies of 60-76% (DOTA) and 40-47% (CB-TE2A). (64)Cu-micelles were injected into tumor-bearing mice (8 mg/kg) and PET/CT scans were carried out at 1, 22, and 46 h postinjection. The micelles showed good blood stability (T1/2: 20-26 h) and tumor uptake that was comparable with other nanoparticle systems. The DOTA micelles showed a biodistribution similar to the CB-TE2A micelles and the tumor uptake was comparable for both micelle types at 1 h (1.9% ID/g) and 22 h (3.9% ID/g) but diverged at 46 h with 3.6% ID/g (DOTA) and 4.9% ID/g (CB-TE2A). On the basis of our data, we conclude that cross-linked PEG-PHEMA-PCMA micelles have long circulating properties resulting in tumor accumulation and that DOTA and CB-TE2A (64)Cu-chelates show similar in vivo stability for the studied micelle system.

OriginalsprogEngelsk
TidsskriftBiomacromolecules
Vol/bind15
Udgave nummer5
Sider (fra-til)1625-33
Antal sider9
ISSN1525-7797
DOI
StatusUdgivet - 2014

Emneord

  • Animals
  • Chelating Agents
  • Coordination Complexes
  • Copper Radioisotopes
  • Disease Models, Animal
  • Drug Carriers
  • Female
  • Glioblastoma
  • Heterocyclic Compounds, 1-Ring
  • Mice
  • Mice, Nude
  • Micelles
  • Nanoparticles
  • Neoplasms, Experimental
  • Organometallic Compounds
  • Polymers
  • Positron-Emission Tomography
  • Ultraviolet Rays

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