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.
Originalsprog | Engelsk |
---|---|
Tidsskrift | Biomacromolecules |
Vol/bind | 15 |
Udgave nummer | 5 |
Sider (fra-til) | 1625-33 |
Antal sider | 9 |
ISSN | 1525-7797 |
DOI | |
Status | Udgivet - 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