Fast synthesis and bioconjugation of 68Ga core-doped extremely small iron oxide nanoparticles for PET/MR imaging

Combination of complementary imaging techniques, like hybrid PET/MRI, allows protocols to be developed that exploit the best features of both. In order to get the best of these combinations the use of dual probes is highly desirable. On this sense the combination of biocompatible iron oxide nanoparticles and 68Ga isotope is a powerful development for the new generation of hybrid systems and multimodality approaches. Our objective was the synthesis and application of a chelator-free 68Ga-iron oxide nanotracer with improved stability, radiolabeling yield and in vivo performance in dual PET/MRI. We carried out the core doping of iron oxide nanoparticles, without the use of any chelator, by a microwave-driven protocol. The synthesis allowed the production of extremely small (2.5 nm) 68Ga core-doped iron oxide nanoparticles. The microwave approach allowed an extremely fast synthesis with a 90% radiolabeling yield and T1 contrast in MRI. With the same microwave approach the nano-radiotracer was functionalized in a fast and efficient way. We finally evaluated these dual targeting nanoparticles in an angiogenesis murine model by PET/MR imaging.This work was supported by a grant from Spanish ministry of economy (MAT2013‐47303‐P and SAF2012‐1207), Fundació La Marató de TV3 (70/C/2012), by a grant from the Comunidad de Madrid (S2010/BMD‐2326, Inmunothercan‐CM and CAM/API1009). EA.hy926 cells were kindly provided by Dr. C‐J. S. Edgell, University of North Carolina. SC is recipient of a fellowship from the Marie Curie Actions – PEOPLE ‐ COFUND Programme. The CNIC is supported by the Ministerio de Economía y Competitividad and the Pro‐CNIC Foundation