Efficient Radiolabeling of Block Copolymer Micelles through Radiometal Salt Precipitation for Theranostic Applications

Efficient Radiolabeling of Block Copolymer Micelles through Radiometal Salt Precipitation for Theranostic Applications

Liu, H. (TU Delft RST/Applied Radiation & Isotopes)
de Kruijff, R.M. (TU Delft RST/Applied Radiation & Isotopes)
Laan, A.C. (TU Delft RST/Technici Pool)
Beekman, F.J. (TU Delft RST/Biomedical Imaging; MILabs B.V.; University Medical Center Utrecht)
van den Heuvel, E.J. (TU Delft RST/Technici Pool)
Ramakers, R.M. (TU Delft RST/Technici Pool; MILabs B.V.; University Medical Center Utrecht)
Eelkema, R. (TU Delft ChemE/Advanced Soft Matter)
Denkova, A.G. (TU Delft RST/Applied Radiation & Isotopes)

2022

A variety of polymer micelles are designed for the delivery of chemotherapeutic drugs to tumors. Although the promise of these nanocarriers is very high, in the clinic the effectivity is rather limited. Determining the in vivo fate of the micelles can greatly help to improve this treatment. Here, a simple and fast chelator-free method for radiolabeling of polymer micelles composed of different block copolymers is presented, which can allow evaluating the behavior of the nanocarriers in vivo using noninvasive nuclear imaging techniques (e.g., single photon computed tomography, SPECT). The radiolabeling method consists of adding the radioisotope ions, i.e., ¹¹¹In(III), resulting in a high radiolabeling efficiencies up to 90%. The results suggest that the radiolabeling efficiency depends on two important factors: the properties of the hydrophobic block in the block copolymer composing the micelle core, and the speciation of the radiometal salts. The formation of metal hydroxides and their precipitation in the core of the micelles appears to be a key factor for high stability. Moreover, the method can be applied to radiolabel the micelles in the presence of chemotherapeutic drugs. Finally, a SPECT study shows that the radiolabeled samples are stable in vivo without any evident loss of ¹¹¹In(III).

biodistribution
block copolymer
hydrophobicity
radiolabeling
SPECT imaging

http://resolver.tudelft.nl/uuid:a8ddc0e5-f9e2-45ed-9e1d-c696e9cda5b4

https://doi.org/10.1002/adtp.202200077

Advanced Therapeutics, 5 (9)

Institutional Repository

journal article

© 2022 H. Liu, R.M. de Kruijff, A.C. Laan, F.J. Beekman, E.J. van den Heuvel, R.M. Ramakers, R. Eelkema, A.G. Denkova