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Remote-loading of liposomes with manganese-52 and in vivo evaluation of the stabilities of 52 Mn-DOTA and 64 Cu-DOTA using radiolabelled liposomes and PET imaging.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2018 Jan 10; Vol. 269, pp. 100-109. Date of Electronic Publication: 2017 Nov 06. - Publication Year :
- 2018
-
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 ( <superscript>52</superscript> Mn, T½=5.6days), allow the imaging of this biodistribution. We report optimized protocols for radiolabeling liposomes with <superscript>52</superscript> Mn, through both remote-loading and surface labeling. For comparison, liposomes were also remote-loaded and surface labeled with copper-64 ( <superscript>64</superscript> Cu, 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 <superscript>52</superscript> Mn-DOTA and <superscript>64</superscript> Cu-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 <superscript>52</superscript> Mn 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 <superscript>52</superscript> Mn-DOTA exhibited a significantly shorter plasma half-life (T <subscript>½</subscript> =14.4h) when compared to the remote-loaded counterpart (T <subscript>½</subscript> =21.3h), whereas surface-conjugated <superscript>64</superscript> Cu-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 <superscript>52</superscript> Mn, and furthermore that <superscript>52</superscript> Mn-DOTA may be unstable in vivo whereas <superscript>64</superscript> Cu-DOTA appears suitable for quantitative imaging.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cell Line, Tumor
Chelating Agents pharmacokinetics
Copper Radioisotopes pharmacokinetics
Heterocyclic Compounds, 1-Ring pharmacokinetics
Liposomes
Manganese pharmacokinetics
Mice, Inbred BALB C
Neoplasms diagnostic imaging
Positron-Emission Tomography
Radioisotopes pharmacokinetics
Radiopharmaceuticals pharmacokinetics
Tissue Distribution
Chelating Agents administration & dosage
Copper Radioisotopes administration & dosage
Heterocyclic Compounds, 1-Ring administration & dosage
Manganese administration & dosage
Radioisotopes administration & dosage
Radiopharmaceuticals administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 269
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 29122662
- Full Text :
- https://doi.org/10.1016/j.jconrel.2017.11.006