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89 Zr‐ and Fe‐Labeled Polymeric Micelles for Dual Modality PET and T 1 ‐Weighted MR Imaging
Author(s) -
Starmans Lucas W. E.,
Hummelink Marcus A. P. M.,
Rossin Raffaella,
Kneepkens Esther C. M.,
Lamerichs Rolf,
Donato Katia,
Nicolay Klaas,
Grüll Holger
Publication year - 2015
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201500414
Subject(s) - micelle , in vivo , biodistribution , magnetic resonance imaging , materials science , ex vivo , spect imaging , positron emission tomography , preclinical imaging , drug delivery , chemistry , nuclear magnetic resonance , biomedical engineering , nuclear medicine , medicine , nanotechnology , radiology , aqueous solution , physics , microbiology and biotechnology , biology
In this study, a new 89 Zr‐ and Fe 3+ ‐labeled micelle nanoplatform ( 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 89 Zr‐deferoxamine ( 89 Zr‐DFO) and Fe 3+ ‐deferoxamine (Fe‐DFO) for PET and MR purposes, respectively. 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 1 ‐contrast label instead of commonly used Gd 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 89 Zr/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 89 Zr/Fe‐DFO‐micelles at high resolution. In summary, the 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.