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Laan AC, Santini C, Jennings L, et al. Radiolabeling polymeric micelles for in vivo evaluation: a novel, fast, and facile method. EJNMMI Res. 2016;6(1):12doi: 10.1186/s13550-016-0167-x.
Laan, A. C., Santini, C., Jennings, L., de Jong, M., Bernsen, M. R., & Denkova, A. G. (2016). Radiolabeling polymeric micelles for in vivo evaluation: a novel, fast, and facile method. EJNMMI research, 6(1), 12. https://doi.org/10.1186/s13550-016-0167-x
Laan, Adrianus C, et al. "Radiolabeling polymeric micelles for in vivo evaluation: a novel, fast, and facile method." EJNMMI research vol. 6,1 (2016): 12. doi: https://doi.org/10.1186/s13550-016-0167-x
Laan AC, Santini C, Jennings L, de Jong M, Bernsen MR, Denkova AG. Radiolabeling polymeric micelles for in vivo evaluation: a novel, fast, and facile method. EJNMMI Res. 2016 Dec;6(1):12. doi: 10.1186/s13550-016-0167-x. Epub 2016 Feb 09. PMID: 26860294; PMCID: PMC4747947.
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EJNMMI Res. 2016 Dec;6(1):12. doi: 10.1186/s13550-016-0167-x. Epub 2016 Feb 09.

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

EJNMMI research

Adrianus C Laan, Costanza Santini, Laurence Jennings, Marion de Jong, Monique R Bernsen, Antonia G Denkova

Affiliations

  1. Department of Radiation Science and Technology, Delft University of Technology, Mekelweg 15, 2629 JB, Delft, The Netherlands. [email protected].
  2. Department of Radiology, Erasmus Medical Center, Dr. Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands.
  3. Institut Charles Sadron (UPR22-CNRS), 23 Rue du Loess, 67034, Strasbourg Cedex 2, France.
  4. Department of Radiation Science and Technology, Delft University of Technology, Mekelweg 15, 2629 JB, Delft, The Netherlands.

PMID: 26860294 PMCID: PMC4747947 DOI: 10.1186/s13550-016-0167-x

Abstract

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., (111)In) 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 (111)In 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 (111)In. 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.

Keywords: Amphiphilic diblock copolymers; Polymeric micelles; Radiolabeling; SPECT

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