Jensen, Andreas Tue Ingemann2; Binderup, Tina6; Ek, Pramod Kumar7; Kjær, Andreas6; Rasmussen, Palle3; Andresen, Thomas Lars1
1 Department of Micro- and Nanotechnology, Technical University of Denmark2 Center for Nuclear Technologies, Technical University of Denmark3 The Hevesy Laboratory, Center for Nuclear Technologies, Technical University of Denmark4 Center for Nanomedicine and Theranostics, Center, Technical University of Denmark5 Colloids and Biological Interfaces, Department of Micro- and Nanotechnology, Technical University of Denmark6 Copenhagen University Hospital7 Risø National Laboratory for Sustainable Energy, Technical University of Denmark
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 64Cu in micelle nanoparticles. The coumarin polymer (PCMA-block) micelle core was cross-linked by UV irradiation at 2 W/cm2 for 30 min. The cross-linked micelles were labeled with 64Cu 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). 64Cu-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 64Cu-chelates show similar in vivo stability for the studied micelle system.
Biomacromolecules, 2014, Vol 15, Issue 5, p. 1625-33