Remote-loading of liposomes with manganese-52 and in vivo evaluation of the stabilities of 52Mn-DOTA and 64Cu-DOTA using radiolabelled liposomes and PET imaging

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Remote-loading of liposomes with manganese-52 and in vivo evaluation of the stabilities of 52Mn-DOTA and 64Cu-DOTA using radiolabelled liposomes and PET imaging. / Jensen, Andreas I; Severin, Gregory W; Hansen, Anders E; Fliedner, Frederikke P; Eliasen, Rasmus; Parhamifar, Ladan; Kjær, Andreas; Andresen, Thomas L; Henriksen, Jonas R.

In: Journal of Controlled Release, Vol. 269, 2018, p. 100-109.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Jensen, AI, Severin, GW, Hansen, AE, Fliedner, FP, Eliasen, R, Parhamifar, L, Kjær, A, Andresen, TL & Henriksen, JR 2018, 'Remote-loading of liposomes with manganese-52 and in vivo evaluation of the stabilities of 52Mn-DOTA and 64Cu-DOTA using radiolabelled liposomes and PET imaging', Journal of Controlled Release, vol. 269, pp. 100-109. https://doi.org/10.1016/j.jconrel.2017.11.006

APA

Jensen, A. I., Severin, G. W., Hansen, A. E., Fliedner, F. P., Eliasen, R., Parhamifar, L., Kjær, A., Andresen, T. L., & Henriksen, J. R. (2018). Remote-loading of liposomes with manganese-52 and in vivo evaluation of the stabilities of 52Mn-DOTA and 64Cu-DOTA using radiolabelled liposomes and PET imaging. Journal of Controlled Release, 269, 100-109. https://doi.org/10.1016/j.jconrel.2017.11.006

Vancouver

Jensen AI, Severin GW, Hansen AE, Fliedner FP, Eliasen R, Parhamifar L et al. Remote-loading of liposomes with manganese-52 and in vivo evaluation of the stabilities of 52Mn-DOTA and 64Cu-DOTA using radiolabelled liposomes and PET imaging. Journal of Controlled Release. 2018;269:100-109. https://doi.org/10.1016/j.jconrel.2017.11.006

Author

Jensen, Andreas I ; Severin, Gregory W ; Hansen, Anders E ; Fliedner, Frederikke P ; Eliasen, Rasmus ; Parhamifar, Ladan ; Kjær, Andreas ; Andresen, Thomas L ; Henriksen, Jonas R. / Remote-loading of liposomes with manganese-52 and in vivo evaluation of the stabilities of 52Mn-DOTA and 64Cu-DOTA using radiolabelled liposomes and PET imaging. In: Journal of Controlled Release. 2018 ; Vol. 269. pp. 100-109.

Bibtex

@article{97c7bc15407b473a945dced040977d31,
title = "Remote-loading of liposomes with manganese-52 and in vivo evaluation of the stabilities of 52Mn-DOTA and 64Cu-DOTA using radiolabelled liposomes and PET imaging",
abstract = "Liposomes are nanoparticles used in drug delivery that distribute over several days in humans and larger animals. Radiolabeling with long-lived positron emission tomography (PET) radionuclides, such as manganese-52 (52Mn, T½=5.6days), allow the imaging of this biodistribution. We report optimized protocols for radiolabeling liposomes with 52Mn, through both remote-loading and surface labeling. For comparison, liposomes were also remote-loaded and surface labeled with copper-64 (64Cu, T½=12.7h) through conventional means. The chelator DOTA was used in all cases. The in vivo stability of radiometal chelates is widely debated but studies that mimic a realistic in vivo setting are lacking. Therefore, we employed these four radiolabeled liposome types as platforms to demonstrate a new concept for such in vivo evaluation, here of the chelates 52Mn-DOTA and 64Cu-DOTA. This was done by comparing {"}shielded{"} remote-loaded with {"}exposed{"} surface labeled variants in a CT26 tumor-bearing mouse model. Remote loading (90min at 55°C) and surface labeling (55°C for 2h) of 52Mn gave excellent radiolabeling efficiencies of 97-100% and 98-100% respectively, and the liposome biodistribution was imaged by PET for up to 8days. Liposomes with surface-conjugated 52Mn-DOTA exhibited a significantly shorter plasma half-life (T½=14.4h) when compared to the remote-loaded counterpart (T½=21.3h), whereas surface-conjugated 64Cu-DOTA cleared only slightly faster and non-significantly, when compared to remote-loaded (17.2±2.9h versus 20.3±1.2h). From our data, we conclude the successful remote-loading of liposomes with 52Mn, and furthermore that 52Mn-DOTA may be unstable in vivo whereas 64Cu-DOTA appears suitable for quantitative imaging.",
keywords = "Animals, Cell Line, Tumor, Chelating Agents/administration & dosage, Copper Radioisotopes/administration & dosage, Heterocyclic Compounds, 1-Ring/administration & dosage, Liposomes, Manganese/administration & dosage, Mice, Inbred BALB C, Neoplasms/diagnostic imaging, Positron-Emission Tomography, Radioisotopes/administration & dosage, Radiopharmaceuticals/administration & dosage, Tissue Distribution",
author = "Jensen, {Andreas I} and Severin, {Gregory W} and Hansen, {Anders E} and Fliedner, {Frederikke P} and Rasmus Eliasen and Ladan Parhamifar and Andreas Kj{\ae}r and Andresen, {Thomas L} and Henriksen, {Jonas R}",
note = "Copyright {\textcopyright} 2017 Elsevier B.V. All rights reserved.",
year = "2018",
doi = "10.1016/j.jconrel.2017.11.006",
language = "English",
volume = "269",
pages = "100--109",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Remote-loading of liposomes with manganese-52 and in vivo evaluation of the stabilities of 52Mn-DOTA and 64Cu-DOTA using radiolabelled liposomes and PET imaging

AU - Jensen, Andreas I

AU - Severin, Gregory W

AU - Hansen, Anders E

AU - Fliedner, Frederikke P

AU - Eliasen, Rasmus

AU - Parhamifar, Ladan

AU - Kjær, Andreas

AU - Andresen, Thomas L

AU - Henriksen, Jonas R

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2018

Y1 - 2018

N2 - Liposomes are nanoparticles used in drug delivery that distribute over several days in humans and larger animals. Radiolabeling with long-lived positron emission tomography (PET) radionuclides, such as manganese-52 (52Mn, T½=5.6days), allow the imaging of this biodistribution. We report optimized protocols for radiolabeling liposomes with 52Mn, through both remote-loading and surface labeling. For comparison, liposomes were also remote-loaded and surface labeled with copper-64 (64Cu, T½=12.7h) through conventional means. The chelator DOTA was used in all cases. The in vivo stability of radiometal chelates is widely debated but studies that mimic a realistic in vivo setting are lacking. Therefore, we employed these four radiolabeled liposome types as platforms to demonstrate a new concept for such in vivo evaluation, here of the chelates 52Mn-DOTA and 64Cu-DOTA. This was done by comparing "shielded" remote-loaded with "exposed" surface labeled variants in a CT26 tumor-bearing mouse model. Remote loading (90min at 55°C) and surface labeling (55°C for 2h) of 52Mn gave excellent radiolabeling efficiencies of 97-100% and 98-100% respectively, and the liposome biodistribution was imaged by PET for up to 8days. Liposomes with surface-conjugated 52Mn-DOTA exhibited a significantly shorter plasma half-life (T½=14.4h) when compared to the remote-loaded counterpart (T½=21.3h), whereas surface-conjugated 64Cu-DOTA cleared only slightly faster and non-significantly, when compared to remote-loaded (17.2±2.9h versus 20.3±1.2h). From our data, we conclude the successful remote-loading of liposomes with 52Mn, and furthermore that 52Mn-DOTA may be unstable in vivo whereas 64Cu-DOTA appears suitable for quantitative imaging.

AB - Liposomes are nanoparticles used in drug delivery that distribute over several days in humans and larger animals. Radiolabeling with long-lived positron emission tomography (PET) radionuclides, such as manganese-52 (52Mn, T½=5.6days), allow the imaging of this biodistribution. We report optimized protocols for radiolabeling liposomes with 52Mn, through both remote-loading and surface labeling. For comparison, liposomes were also remote-loaded and surface labeled with copper-64 (64Cu, T½=12.7h) through conventional means. The chelator DOTA was used in all cases. The in vivo stability of radiometal chelates is widely debated but studies that mimic a realistic in vivo setting are lacking. Therefore, we employed these four radiolabeled liposome types as platforms to demonstrate a new concept for such in vivo evaluation, here of the chelates 52Mn-DOTA and 64Cu-DOTA. This was done by comparing "shielded" remote-loaded with "exposed" surface labeled variants in a CT26 tumor-bearing mouse model. Remote loading (90min at 55°C) and surface labeling (55°C for 2h) of 52Mn gave excellent radiolabeling efficiencies of 97-100% and 98-100% respectively, and the liposome biodistribution was imaged by PET for up to 8days. Liposomes with surface-conjugated 52Mn-DOTA exhibited a significantly shorter plasma half-life (T½=14.4h) when compared to the remote-loaded counterpart (T½=21.3h), whereas surface-conjugated 64Cu-DOTA cleared only slightly faster and non-significantly, when compared to remote-loaded (17.2±2.9h versus 20.3±1.2h). From our data, we conclude the successful remote-loading of liposomes with 52Mn, and furthermore that 52Mn-DOTA may be unstable in vivo whereas 64Cu-DOTA appears suitable for quantitative imaging.

KW - Animals

KW - Cell Line, Tumor

KW - Chelating Agents/administration & dosage

KW - Copper Radioisotopes/administration & dosage

KW - Heterocyclic Compounds, 1-Ring/administration & dosage

KW - Liposomes

KW - Manganese/administration & dosage

KW - Mice, Inbred BALB C

KW - Neoplasms/diagnostic imaging

KW - Positron-Emission Tomography

KW - Radioisotopes/administration & dosage

KW - Radiopharmaceuticals/administration & dosage

KW - Tissue Distribution

U2 - 10.1016/j.jconrel.2017.11.006

DO - 10.1016/j.jconrel.2017.11.006

M3 - Journal article

C2 - 29122662

VL - 269

SP - 100

EP - 109

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -

ID: 215369726