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 89Zr4+ (t1/2 = 78.41 h) ions and applications in dual‐modality positron emission tomography/magnetic resonance imaging (PET/MRI). Experimental properties of [89Zr]GdDOTAGA–ZrDFO–GNF–trastuzumab are tested in extensive chemical, spectroscopic, radiochemical, and cellular assays in vitro, 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. Pristine graphene nanoflakes with a carboxylated edge are functionalized with tumor‐specific antibodies and are used as scaffolds to develop multimodality agents for positron emission tomography/magnetic resonance imaging (PET/MRI). Antibody conjugation facilitates control over the tracer pharmacokinetics with increased circulation times, and enhanced drug delivery to the tumors.