Conference paper
Gold Nanoparticles with Stably Embedded Cu-64 and Their Use in Nanoparticle Research
Technical University of Denmark1
Center for Nuclear Technologies, Technical University of Denmark2
The Hevesy Laboratory, Center for Nuclear Technologies, Technical University of Denmark3
University of Copenhagen4
Department of Micro- and Nanotechnology, Technical University of Denmark5
Colloids and Biological Interfaces, Department of Micro- and Nanotechnology, Technical University of Denmark6
64Cu is a popular radionuclide for PET imaging and when 64Cu2+ is mixed with gold nanoparticles (AuNPs) it adheres to the gold surface. Taking advantage of this, we developed methods to trap the 64Cu within the AuNPs by embedding under additional layers of gold. This resulted in radiolabeling efficiencies around 53 ± 6%.
EDTA challenge for two days revealed the embedded 64Cu to possess excellent stability with 94-98% of the radioactivity remaining associated with the AuNPs. Testing for two days against serum likewise showed no loss of 64Cu from the 64Cu-AuNPs. Accordingly, the technology was shown to yield a very stable radiolabel that can accurately trace AuNPs in vivo.
Such chelator-free radiolabeling removes traditional concerns over the use of chelators for 64Cu, notably instabilities of chelators, such as DOTA, and their ability to alter the surface and thus the biodistribution of the compounds onto which they are attached. Radiolabeled 64Cu-AuNPs were prepared in biomedically relevant sizes of 20-30 nm and decorated with three different coatings, in order to investigate their in vivo performance by PET imaging in a murine xenograft model.
We found the longest plasma half-life (T½ about 9 hours) to result from a polyethylene glycol (PEG) coating, while faster elimination from the bloodstream was observed for both a Tween-20 stabilized coating and a zwitterionic coating based on sulfonic acids and quaternary amines. Accordingly, our data concluded the PEG coating to be most benefical for long circulation in vivo.
In the in vivo model, the 64Cu was observed to closely follow the AuNPs for each coating, again attributing to the excellent stability of the radiolabel. Further, 64Cu-AuNPs were prepared in three different sizes ranging from 30 to 70 nm and injected intravenously (I.V.) or intratumorally (I.T.) in murine xenograft models, either coated with PEG or stabilized by citrate (only 30 nm).
In the I.T. experiments, citrate-stabilized 64Cu-AuNPs were retained best in the tumors with about 100 %ID/g after 24 hours. For the PEG-coated 64Cu-AuNPs, a tendency for increased retention as larger particles were injected was observed (30 nm: ~ 30 %ID/g, 70 nm: ~ 60%ID/g). In the I.V. experiments, the opposite tendency was observed, with smaller particles showing higher tumor accumulation and citrate stabilized 64Cu-AuNPs being rapidly taken up in liver and spleen.
Our group continues work with embedding of radionuclides in solid nanoparticles and further results will be presented as available.
Language: | English |
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Year: | 2016 |
Proceedings: | 29th Annual Congress of the European Association of Nuclear Medicine |
ISSN: | 16197089 and 16197070 |
Types: | Conference paper |
DOI: | 10.1007/s00259-016-3484-4 |
ORCIDs: | Severin, Gregory , Kempen, Paul and Andresen, Thomas Lars |