A Mouse Positron Emission Tomography Study of the Biodistribution of Gold Nanoparticles with Different Surface Coatings Using Embedded Copper-64

Research output: Contribution to journalJournal article – Annual report year: 2016Researchpeer-review

Standard

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{fe4705512a5b4aa0b3a0ed9fc481f916,
title = "A Mouse Positron Emission Tomography Study of the Biodistribution of Gold Nanoparticles with Different Surface Coatings Using Embedded Copper-64",
abstract = "By taking advantage of the ability of (64)Cu to bind non-specifically to gold surfaces, we have developed a new methodology to embed this radionuclide inside gold nanoparticles (AuNPs). (64)Cu enables the in vivo imaging of AuNPs by positron emission tomography (PET). AuNPs have a multitude of uses within health technology and are useful tools for general nanoparticle research. (64)Cu-AuNPs were prepared by incubating AuNP seeds with (64)Cu(2+), followed by the entrapment of the radionuclide by grafting a second layer of gold on the surface. This resulted in radiolabeling efficiencies of 53 ± 6{\%}. The radiolabel showed excellent stability when challenging with EDTA for two days (>95{\%} radioactivity retention) and showed no loss of (64)Cu when incubated with 50{\%} mouse serum for two days. The methodology was chelator-free, and circumvents traditional concerns over chelator instability and altered AuNP properties due to surface modification. Radiolabeled (64)Cu-AuNP cores were prepared in a biomedically relevant size of 30 nm and used to investigate the in vivo stability of three different AuNP coatings by PET imaging in a murine xenograft tumor model. We found the longest plasma half-life (T½ = 9 hours) and highest tumor accumulation (3.9 {\%}ID/g) by using polyethylene glycol (PEG) coating, while faster elimination from the bloodstream was observed with both a Tween 20-stabilized coating and a zwitterionic coating based on a mixture of sulfonic acids and quaternary amines, which has previously been reported to be superior to PEG. The new embedding method provides the utilization of PET imaging in combination with the multituide of uses that AuNPs have found in health technology, and the method can equally well be utilized for therapeutic copper radioisotopes for use in radiotherapy.",
keywords = "Gold Nanoparticles, Copper-64, PET, Intrinsic Radiolabeling, Coating Materials",
author = "Frellsen, {Anders Floor} and Hansen, {Anders Elias} and J{\o}lck, {Rasmus Irming} and Paul Kempen and Severin, {Gregory W} and Rasmussen, {Palle H} and Andreas Kj{\ae}r and Jensen, {Andreas Tue Ingemann} and Andresen, {Thomas Lars}",
year = "2016",
doi = "10.1021/acsnano.6b03144",
language = "English",
journal = "A C S Nano",
issn = "1936-0851",
publisher = "American Chemical Society",

}

RIS

TY - JOUR

T1 - A Mouse Positron Emission Tomography Study of the Biodistribution of Gold Nanoparticles with Different Surface Coatings Using Embedded Copper-64

AU - Frellsen, Anders Floor

AU - Hansen, Anders Elias

AU - Jølck, Rasmus Irming

AU - Kempen, Paul

AU - Severin, Gregory W

AU - Rasmussen, Palle H

AU - Kjær, Andreas

AU - Jensen, Andreas Tue Ingemann

AU - Andresen, Thomas Lars

PY - 2016

Y1 - 2016

N2 - By taking advantage of the ability of (64)Cu to bind non-specifically to gold surfaces, we have developed a new methodology to embed this radionuclide inside gold nanoparticles (AuNPs). (64)Cu enables the in vivo imaging of AuNPs by positron emission tomography (PET). AuNPs have a multitude of uses within health technology and are useful tools for general nanoparticle research. (64)Cu-AuNPs were prepared by incubating AuNP seeds with (64)Cu(2+), followed by the entrapment of the radionuclide by grafting a second layer of gold on the surface. This resulted in radiolabeling efficiencies of 53 ± 6%. The radiolabel showed excellent stability when challenging with EDTA for two days (>95% radioactivity retention) and showed no loss of (64)Cu when incubated with 50% mouse serum for two days. The methodology was chelator-free, and circumvents traditional concerns over chelator instability and altered AuNP properties due to surface modification. Radiolabeled (64)Cu-AuNP cores were prepared in a biomedically relevant size of 30 nm and used to investigate the in vivo stability of three different AuNP coatings by PET imaging in a murine xenograft tumor model. We found the longest plasma half-life (T½ = 9 hours) and highest tumor accumulation (3.9 %ID/g) by using polyethylene glycol (PEG) coating, while faster elimination from the bloodstream was observed with both a Tween 20-stabilized coating and a zwitterionic coating based on a mixture of sulfonic acids and quaternary amines, which has previously been reported to be superior to PEG. The new embedding method provides the utilization of PET imaging in combination with the multituide of uses that AuNPs have found in health technology, and the method can equally well be utilized for therapeutic copper radioisotopes for use in radiotherapy.

AB - By taking advantage of the ability of (64)Cu to bind non-specifically to gold surfaces, we have developed a new methodology to embed this radionuclide inside gold nanoparticles (AuNPs). (64)Cu enables the in vivo imaging of AuNPs by positron emission tomography (PET). AuNPs have a multitude of uses within health technology and are useful tools for general nanoparticle research. (64)Cu-AuNPs were prepared by incubating AuNP seeds with (64)Cu(2+), followed by the entrapment of the radionuclide by grafting a second layer of gold on the surface. This resulted in radiolabeling efficiencies of 53 ± 6%. The radiolabel showed excellent stability when challenging with EDTA for two days (>95% radioactivity retention) and showed no loss of (64)Cu when incubated with 50% mouse serum for two days. The methodology was chelator-free, and circumvents traditional concerns over chelator instability and altered AuNP properties due to surface modification. Radiolabeled (64)Cu-AuNP cores were prepared in a biomedically relevant size of 30 nm and used to investigate the in vivo stability of three different AuNP coatings by PET imaging in a murine xenograft tumor model. We found the longest plasma half-life (T½ = 9 hours) and highest tumor accumulation (3.9 %ID/g) by using polyethylene glycol (PEG) coating, while faster elimination from the bloodstream was observed with both a Tween 20-stabilized coating and a zwitterionic coating based on a mixture of sulfonic acids and quaternary amines, which has previously been reported to be superior to PEG. The new embedding method provides the utilization of PET imaging in combination with the multituide of uses that AuNPs have found in health technology, and the method can equally well be utilized for therapeutic copper radioisotopes for use in radiotherapy.

KW - Gold Nanoparticles

KW - Copper-64

KW - PET

KW - Intrinsic Radiolabeling

KW - Coating Materials

U2 - 10.1021/acsnano.6b03144

DO - 10.1021/acsnano.6b03144

M3 - Journal article

JO - A C S Nano

JF - A C S Nano

SN - 1936-0851

ER -