Radiolabeling polymeric micelles for in vivo evaluation: A novel, fast, and facile method

Radiolabeling polymeric micelles for in vivo evaluation: A novel, fast, and facile method

Laan, A.C.
Santini, C.
Jennings, L.
De Jong, M.
Bernsen, M.R.
Denkova, A.G.

Applied Sciences

RST/Radiation, Science and Technology

2016-02-09

Background Single photon emission computed tomography (SPECT) is an indispensable tool in the determination of the in vivo fate of polymeric micelles. However, for this purpose, the micelles need to be radiolabeled, and almost all radiolabeling procedures published to date involve the conjugation of a chelating agent to the constituting polymer, which could actually affect their biodistribution. In this paper, we report a new facile method for radiolabeling polystyrene-b-poly(ethylene oxide) diblock copolymer micelles without the necessity of any chemical modification. Instead, we entrap the radiolabel (i.e., 111In) in the micellar core during the formation of the micelles by using tropolone as lipophilic ligand. Methods Micelles were prepared by emulsifying a polymer solution in chloroform with a buffer containing 111In and lipophilic ligand tropolone, by stirring for about 2 h. The produced micelles were physically characterized by means of dynamic light scattering and transmission electron microscopy. The biological properties of the radiolabeled micelles were determined by means of in vivo and ex vivo evaluation. SPECT analysis was done on Balb/c-nu mice, after administration of 1 mg micelles containing 22 MBq of 111In. SPECT images were obtained over 24 h. Biodistribution of the micelles was assessed also ex vivo. Results The radiolabeling method is robust and reproducible with constant radiolabeling efficiency (~30 %) even at indium concentrations that are much higher than the necessary for in vivo studies, and the radiolabel retention is more than 80 % in mouse serum at 48 h. Radiolabeled micelles having hydrodynamic radius of 97?±?13 nm have been successfully evaluated in vivo and ex vivo in non-tumor-bearing mice, revealing significant blood circulation up to at least 24 h post injection, with low accumulation in most organs except for the liver and spleen, which are the natural organs for clearance of nanoparticles. Conclusions An easy and robust radiolabeling method has been developed, and its applicability is demonstrated in animal studies, showing its value for future investigation of polymeric micelles as nanocarriers in tumor-bearing mice.

radiolabeling
polymeric micelles
aAmphiphilic diblock copolymers
SPECT
OA-Fund TU Delft

http://resolver.tudelft.nl/uuid:fde4650e-7764-47e5-bb72-9e2dd8f6ada5

SpringerOpen

2191-219X

https://doi.org/10.1186/s13550-016-0167-x

EJNMMI Research, 6, 2016

Institutional Repository

journal article

© 2016 The Author(s)
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)