Graphene Nanoflake Antibody Conjugates for Multimodal Imaging of Tumors

Graphene-based materials are promising scaffolds for use in the design of tailored-made nanomedicines. Herein, the synthesis and characterization of a series of multifunctional carboxylated graphene nanoflakes (GNFs) conjugated to monoclonal antibodies (mAbs) for tumor-specific binding and modulation of pharmacokinetics is presented. GNF-mAb constructs are coupled to a fluorophore (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene [BODIPY]) for applications in optical imaging, a paramagnetic Gd3+ complex, [GdDOTAGA(H2O)](-), and the hexadentate chelate desferrioxamine B (DFO) for radiolabeling with Zr-89(4+) (t(1/2)=78.41h) ions and applications in dual-modality positron emission tomography/magnetic resonance imaging (PET/MRI). Experimental properties of [Zr-89]GdDOTAGA-ZrDFO-GNF-trastuzumab are tested in extensive chemical, spectroscopic, radiochemical, and cellular assays invitro, and assessment of the pharmacokinetics by PET imaging in mice bearing a human ovarian cancer model illustrates the potential of using GNF-mAbs to develop multifunctional PET/MRI probes.