TY - JOUR
T1 - 89Zr- and Fe-labeled polymeric micelles for dual modality PET and T1-weighted MR imaging
AU - Starmans, Lucas W.E.
AU - Hummelink, Marcus A.P.M.
AU - Rossin, Raffaella
AU - Kneepkens, Esther C.M.
AU - Lamerichs, Rolf
AU - Donato, Katia
AU - Nicolay, Klaas
AU - Grüll, Holger
PY - 2015/9/1
Y1 - 2015/9/1
N2 - In this study, a new 89Zr- 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 with 89Zr-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 of 89Zr/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 89Zr/Fe-DFO-micelles at high resolution. In summary, the 89Zr/Fe-DFO-micelle nanoparticulate platform allows EPR-based tumor PET/MRI, and, furthermore, holds great potential for PET/MR image guided drug delivery.
AB - In this study, a new 89Zr- 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 with 89Zr-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 of 89Zr/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 89Zr/Fe-DFO-micelles at high resolution. In summary, the 89Zr/Fe-DFO-micelle nanoparticulate platform allows EPR-based tumor PET/MRI, and, furthermore, holds great potential for PET/MR image guided drug delivery.
KW - Iron
KW - MRI
KW - PET
KW - PET/MR imaging, polymeric micelles
KW - Zirconium-89
UR - http://www.scopus.com/inward/record.url?scp=84943449177&partnerID=8YFLogxK
U2 - 10.1002/adhm.201500414
DO - 10.1002/adhm.201500414
M3 - Article
AN - SCOPUS:84943449177
SN - 2192-2640
VL - 4
SP - 2137
EP - 2145
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 14
ER -