Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions

Abstract

The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron-oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T2 MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging.

Incorporation of gallium-68 into the crystal structure of Prussian blue to form K68GaxFe1−x[Fe(CN)6] nanoparticles: toward a novel bimodal PET/MRI imaging agent

“…In general, small molecule-based 68 Ga imaging agents lack the cell-membrane permeability if no carrier or cell-targeting agent is attached to the molecules. 27 This has hampered the progress made in the past two decades in the development of 68 Ga-based PET radiopharmaceuticals for cellular imaging applications. The surface functionalization of a fluorescent dye on these NPs was explored to visualize cellular uptake of Ga@PBNPs in HeLa cells by confocal fluorescence microscopy.…”

Positron emission tomography and nanotechnology: A dynamic duo for cancer theranostics

“…[32] Their inability to absorb wavelengths in the electromagnetic spectrum and non-interference with the magnetic fields has been utilized in complexing with other functional nanomaterials and drugs to design multifunctional agents (Table 2). [33–35] Moreover, high surface area-to-volume ratio, rigid and stable skeletal network and well-established, scalable synthetic procedures are added advantages, propelling their application as contrast agents in cancer theranostics.…”

“…Taking advantage of the easily tailorable chemistry of silica, Burke et al synthesized 68 Ga radiolabeled silica coated iron oxide nanorods to combine the high sensitivity of PET with MR contrast. [35] As with 89 Zr, 68 Ga is a hard Lewis acid that coordinates easily and stably with the Lewis base donor atoms like oxygen from the silanol groups. PEG modified nanoconjugates were further used for high sensitivity liver imaging.…”

Nanoparticles and radiotracers: advances toward radionanomedicine

“…This method is also effective for radiolabeling silica-coated IONP with 68 Ga, showing the versatility of the method. 39 An analogous method for radiolabeling the clinically approved IONP Feraheme, coined heat-induced radiolabeling (HIR) by the authors, was demonstrated and may be a route for radiolabeling other metal oxide NPs with oxophilic tracers. 38 Omitting the IONP core, chelator free loading of 89 Zr was also observed using various molecular weight dextran NPs for PET/CT imaging of lymph node drainage as well as Cerenkov-guided tumor resection.…”