89Zr- and Fe-Labeled Polymeric Micelles for Dual Modality PET and T1-Weighted MR Imaging.
In this study, a new89Zr- and Fe3+-labeled micelle nanoplatform (89Zr/Fe-DFO-micelles) for dual modality position emission tomography/magnetic resonance (PET/MR) imaging is investigated. The nanoplatform consists of self-assembling amphiphilic diblock copolymers that are functionalized with89Zr-deferoxamine (89Zr-DFO) and Fe3+-deferoxamine (Fe-DFO) for PET and MR purposes, respectively.89Zr displays favorable PET imaging characteristics with a 3.3 d half-life suitable for imaging long circulating nanoparticles. The nanoparticles are modified with Fe-DFO as MR T1-contrast label instead of commonly used Gd3+-based chelates. As these micelles are cleared by liver and spleen, any long term Gd- related toxicity such as nephrogenic systemic fibrosis is avoided. As a proof of concept, an in vivo PET/MR study in mice is presented showing tumor targeting of89Zr/Fe-DFO-micelles through the enhanced permeability and retention (EPR) effect of tumors, yielding high tumor-to-blood (10.3 ± 3.6) and tumor-to-muscle (15.3 ± 8.1) ratios at 48 h post injection. In vivo PET images clearly delineate the tumor tissue and show good correspondence with ex vivo biodistribution results. In vivo magnetic resonance imaging (MRI) allows visualization of the intratumoral distribution of the89Zr/Fe-DFO-micelles at high resolution. In summary, the89Zr/Fe-DFO-micelle nanoparticulate platform allows EPR-based tumor PET/MRI, and, furthermore, holds great potential for PET/MR image guided drug delivery.
Biomedical Engineering, Eindhoven University of Technology, 5656, AE Eindhoven, The Netherlands.
Lucas W E
LWE
Starmans
Biomedical Engineering, Eindhoven University of Technology, 5656, AE Eindhoven, The Netherlands.
Marcus A P M
MAPM
Hummelink
Oncology Solutions, Philips Research, 5656, AE Eindhoven, The Netherlands.
Raffaella
R
Rossin
Biomedical Engineering, Eindhoven University of Technology, 5656, AE Eindhoven, The Netherlands.
Esther C M
ECM
Kneepkens
Oncology Solutions, Philips Research, 5656, AE Eindhoven, The Netherlands.
Rolf
R
Lamerichs
Oncology Solutions, Philips Research, 5656, AE Eindhoven, The Netherlands.
Katia
K
Donato
Biomedical Engineering, Eindhoven University of Technology, 5656, AE Eindhoven, The Netherlands.
Klaas
K
Nicolay
Biomedical Engineering, Eindhoven University of Technology, 5656, AE Eindhoven, The Netherlands.|Oncology Solutions, Philips Research, 5656, AE Eindhoven, The Netherlands.
Holger
H
Grüll
MRI; PET; PET/MR imaging, polymeric micelles; iron; zirconium-89