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

Abstract

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. Copyright © 2016 John Wiley & Sons, Ltd.

Molecular Imaging with 68Ga Radio-Nanomaterials: Shedding Light on Nanoparticles

“…Therefore, reported examples of this methodology use microwave-assisted protocols to synthesize the core-doped iron oxide nanoradiotracers. In 2016, our group reported the synthesis of the first example of 68 Ga core-doped coated iron oxide nanoparticles for PET/MR imaging using microwave technology [72]. In a posterior study in 2017, the same approach was followed using citric acid as coating instead of dextran [73].…”

“…This drawback has focused research on finding methods for developing IONPs that serve as positive contrast agents for T1-weighted MRI. Studies have demonstrated that the downsizing of IONP core or coating thickness causes a shift on the NP magnetic behavior from superparamagnetic towards paramagnetic, thus creating T1-weighted MRI contrast agents [72,[87][88][89].…”

“…Radiochemical purity of the final radiolabeled nanoprobe was higher than 99%. Pellico et al [72] obtained via microwave-assisted synthesis a core-doped hybrid nanoradiotracer, 68 Ga core-doped dextran-coated IONPs, that was posteriorly conjugated to RGD peptide via 1,4-(butanediol) diglycidyl ether homobifunctional crosslinker, to target angiogenesis in a subcutaneous melanoma murine model. To core dope the nanoparticles, 68 GaCl 3 eluate was added to initial precursors and mixture introduced into the microwave for 10 min at 100 • C. Radiolabeling yield obtained was 93.4%.…”

Nanoparticle Functionalization and Its Potentials for Molecular Imaging

“…Therefore, before anatomical changes appear we can detect the formation of disease which is one great advantage over MR imaging. Pellico et al identified that core doping iron oxide particles with 68 gallium, a radioisotope, will make dual modality‐PET/MRI probes 87. NIR Fluorescence Imaging (NIRF) is highly desirable as auto fluorescence by normal tissue is low at that excitation wavelength.…”

Recent advances in the preparation and application of multifunctional iron oxide and liposome-based nanosystems for multimodal diagnosis and therapy

“…In this work, the authors described a microwave-driven synthesis of IONPs doped with 64 Cu. In this case, the radiolabelling yield was modest (33%) giving a low specific activity [63].…”