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

Abstract

BackgroundSingle 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.MethodsMicelles 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.ResultsThe 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.ConclusionsAn 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0167-x) contains supplementary material, which is available to authorized users.

Membrane Radiolabelling of Exosomes for Comparative Biodistribution Analysis in Immunocompetent and Immunodeficient Mice - A Novel and Universal Approach

“…Other cell types such as mesenchymal stem cells 53, 54 and endometrial cells 55 have also been successfully radiolabelled using [ 111 In] Trop. More recently, [ 111 In]Trop was used to label polymeric micelles 56. The orientation of exosomal transmembrane proteins is the same as their parent cells 15 and therefore provides the opportunity for them to be radiolabelled using the same principle.…”

Radiolabeled Nanoparticles in Nuclear Oncology

“…In a facile and robust method developed by Laan et al (2016), tropolone and 111 In were entrapped in the core of micelles, without the surface conjugation of the chelator that might lead to altered biological behavior and compromised stability. Ex vivo biodistribution studies in healthy mice demonstrated high liver and spleen accumulation and significant blood circulation even at 24h post-injection [69].…”

“…Ex vivo biodistribution studies in healthy mice demonstrated high liver and spleen accumulation and significant blood circulation even at 24h post-injection [69]. Micelles crosslinked with pluronic unimers and more specifically poly(ethylene oxide) and poly(propylene oxide) (PEO-PPO-PEO), and radiolabeled with 111 In via DTPA, were studied with respect to in vivo biodistribution using SPECT.…”

In vivo biodistribution of stable spherical and filamentous micelles probed by high-sensitivity SPECT

“…The method used to encapsulate the radioisotope 111 In in the core of the micelles is based on the method developed by Laan et al 30 where the isotope is complexed with the lipophilic chelator tropolone.…”