⁸⁹Zr- and Fe-labeled polymeric micelles for dual modality PET and T₁-weighted MR imaging

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.