期刊
ADVANCED HEALTHCARE MATERIALS
卷 4, 期 14, 页码 2137-2145出版社
WILEY
DOI: 10.1002/adhm.201500414
关键词
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资金
- Center for Translational Molecular Medicine
- Dutch Heart Foundation (PARISK) [01C-202]
- NanoNextNL [FES0901:FES HTSM]
In this study, a new Zr-89- and Fe3+-labeled micelle nanoplatform (Zr-89/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 Zr-89-deferoxamine (Zr-89-DFO) and Fe3+-deferoxamine (Fe-DFO) for PET and MR purposes, respectively. Zr-89 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-1-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 of Zr-89/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 the Zr-89/Fe-DFO-micelles at high resolution. In summary, the Zr-89/Fe-DFO-micelle nanoparticulate platform allows EPR-based tumor PET/MRI, and, furthermore, holds great potential for PET/MR image guided drug delivery.
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