Journal article
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
Center for Nuclear Technologies, Technical University of Denmark1
The Hevesy Laboratory, Center for Nuclear Technologies, Technical University of Denmark2
Department of Micro- and Nanotechnology, Technical University of Denmark3
University of Copenhagen4
Colloids and Biological Interfaces, Department of Micro- and Nanotechnology, Technical University of Denmark5
Department of Chemistry, Technical University of Denmark6
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.
Language: | English |
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Year: | 2018 |
Pages: | 100-109 |
ISSN: | 18734995 and 01683659 |
Types: | Journal article |
DOI: | 10.1016/j.jconrel.2017.11.006 |
ORCIDs: | Jensen, Andreas I. , Severin, Gregory W. , Hansen, Anders Elias , Andresen, Thomas Lars , Henriksen, Jonas Rosager and 0000-0002-2706-5547 |
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid Animals Cell Line, Tumor Chelating Agents Chelating Agents/administration & dosage Copper Radioisotopes Copper Radioisotopes/administration & dosage Heterocyclic Compounds, 1-Ring Heterocyclic Compounds, 1-Ring/administration & dosage Manganese Manganese/administration & dosage Mice, Inbred BALB C Neoplasms Neoplasms/diagnostic imaging Positron-Emission Tomography Radioisotopes Radioisotopes/administration & dosage Radiopharmaceuticals Radiopharmaceuticals/administration & dosage Tissue Distribution