super(89)Zr- and Fe-Labeled Polymeric Micelles for Dual Modality PET and T sub(1)-Weighted MR Imaging

• Published in: Advanced healthcare materials Vol. 4; no. 14; pp. 2137 - 2145
• Main Authors: Starmans, Lucas WE, Hummelink, Marcus APM, Rossin, Raffaella, Kneepkens, Esther CM, Lamerichs, Rolf, Donato, Katia, Nicolay, Klaas, Gruell, Holger
• Format: Journal Article
• Language: English
• Published: 01-10-2015
• Subjects: Biocompatibility; Imaging; In vivo testing; Micelles; Nanostructure; Positron emission; Tomography; Tumors
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201500414

In this study, a new super(89)Zr- and Fe super(3+)-labeled micelle nanoplatform ( super(89)Zr/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 with super(89)Zr-deferoxamine ( super(89)Zr-DFO) and Fe super(3+)-deferoxamine (Fe-DFO) for PET and MR purposes, respectively. super(89)Zr 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 T sub(1)-contrast label instead of commonly used Gd super(3+)-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 of super(89)Zr/Fe-DFO-micelles through the enhanced permeability and retention (EPR) effect of tumors, yielding high tumor-to-blood (10.3 plus or minus 3.6) and tumor-to-muscle (15.3 plus or minus 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 the super(89)Zr/Fe-DFO-micelles at high resolution. In summary, the super(89)Zr/Fe-DFO-micelle nanoparticulate platform allows EPR-based tumor PET/MRI, and, furthermore, holds great potential for PET/MR image guided drug delivery. This study reports on a novel super(89)Zr- and Fe-labeled polymeric micelle nanoplatform ( super(89)Zr/Fe-DFO-micelles) for bimodal positron emission tomography/magnetic resonance (PET/MR) imaging. super(89)Zr/Fe-DFO-micelles clearly delineate tumor tissue in a tumor mouse model using PET/MR imaging. As the nanoparticles are modified with Fe-deferoxamine instead of commonly used Gd super(3+)-based chelates, any long term Gd-related toxicity such as nephrogenic systemic fibrosis is avoided.