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PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice.

Huda P, Binderup T, Pedersen MC, Midtgaard SR, Elema DR, Kjær A, Jensen M, Arleth L - PLoS ONE (2015)

Bottom Line: This makes them promising candidates for both drug delivery purposes and as advanced imaging agents.For the radiolabelling, a simple approach for 64Cu radiolabelling of proteins via a chelating agent, DOTA, was developed.The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold.

View Article: PubMed Central - PubMed

Affiliation: Structural Biophysics, Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, DK-2100 København Ø, Denmark.

ABSTRACT
64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model was used for the investigations, and it was found that the approximately 13 nm nanodiscs, due to their size, permeate deeply into cancer tissue. This makes them promising candidates for both drug delivery purposes and as advanced imaging agents. For the radiolabelling, a simple approach for 64Cu radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold.

No MeSH data available.


Related in: MedlinePlus

Biodistribution of nanodiscs from gamma detection.Assessed by gamma counting 48 hours post injection, n = 10. Dominating accumulation of 64Cu-nanodiscs was found in the kidneys. High accumulation was found in liver and tumor tissue as well.
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pone.0129310.g007: Biodistribution of nanodiscs from gamma detection.Assessed by gamma counting 48 hours post injection, n = 10. Dominating accumulation of 64Cu-nanodiscs was found in the kidneys. High accumulation was found in liver and tumor tissue as well.

Mentions: The nanodiscs were primarily cleared through renal excretion, but the liver and intestinal uptake also reveals some excretion through the hepato-billiary route (Fig 7). Generally, nanoparticles and in particular nanoparticles without PEGylation suffer from recognition by the mononuclear phagocyte system, which results in accumulation in spleen and liver. Despite the nanodisc system being non-PEGylated, only a modest accumulation in the liver and the spleen was observed throughout the 48 hour study period. Accumulation in muscle tissue was low and remained steadily so throughout the experiment. For liver and muscle tissue, no significant alteration was observed throughout the 48 hour observation period, and we did not observe splenic accumulation over time. In fact the splenic uptake was significantly lower 48 hour p.i. compared to 1 hour p.i (p = 0.031).


PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice.

Huda P, Binderup T, Pedersen MC, Midtgaard SR, Elema DR, Kjær A, Jensen M, Arleth L - PLoS ONE (2015)

Biodistribution of nanodiscs from gamma detection.Assessed by gamma counting 48 hours post injection, n = 10. Dominating accumulation of 64Cu-nanodiscs was found in the kidneys. High accumulation was found in liver and tumor tissue as well.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488450&req=5

pone.0129310.g007: Biodistribution of nanodiscs from gamma detection.Assessed by gamma counting 48 hours post injection, n = 10. Dominating accumulation of 64Cu-nanodiscs was found in the kidneys. High accumulation was found in liver and tumor tissue as well.
Mentions: The nanodiscs were primarily cleared through renal excretion, but the liver and intestinal uptake also reveals some excretion through the hepato-billiary route (Fig 7). Generally, nanoparticles and in particular nanoparticles without PEGylation suffer from recognition by the mononuclear phagocyte system, which results in accumulation in spleen and liver. Despite the nanodisc system being non-PEGylated, only a modest accumulation in the liver and the spleen was observed throughout the 48 hour study period. Accumulation in muscle tissue was low and remained steadily so throughout the experiment. For liver and muscle tissue, no significant alteration was observed throughout the 48 hour observation period, and we did not observe splenic accumulation over time. In fact the splenic uptake was significantly lower 48 hour p.i. compared to 1 hour p.i (p = 0.031).

Bottom Line: This makes them promising candidates for both drug delivery purposes and as advanced imaging agents.For the radiolabelling, a simple approach for 64Cu radiolabelling of proteins via a chelating agent, DOTA, was developed.The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold.

View Article: PubMed Central - PubMed

Affiliation: Structural Biophysics, Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, DK-2100 København Ø, Denmark.

ABSTRACT
64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model was used for the investigations, and it was found that the approximately 13 nm nanodiscs, due to their size, permeate deeply into cancer tissue. This makes them promising candidates for both drug delivery purposes and as advanced imaging agents. For the radiolabelling, a simple approach for 64Cu radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold.

No MeSH data available.


Related in: MedlinePlus