title: Nanographene oxide-based radioimmunoconstructs for in vivo targeting and SPECT imaging of HER2-positive tumors.
abstract: Nanographene oxide (NGO) is a novel nano-wall material that tracks to tumors in vivo, and which, as a consequence of its large surface area, has the capacity to carry a large payload. This study explores the use of anti-HER2 antibody (trastuzumab)-conjugated NGO, radiolabeled with (111)In-benzyl-diethylenetriaminepentaacetic acid (BnDTPA) via ππ-stacking, for functional imaging. In two HER2-overexpressing murine models of human breast cancer, high tumor-to-muscle ratio was achieved, resulting in clear visualization of tumor using single-photon emission computed tomography (SPECT). In the BALB/neuT model and in BALB/c nu/nu mice bearing 231/H2N xenografts, tumor accumulation amounted to 12.7 ± 0.67 and 15.0 ± 3.7% of the injected dose/g (%ID/g) of tumor tissue at 72 h, with tumor-to-muscle ratios of 35:1 and 7:1, respectively. Radiolabeled NGO-trastuzumab conjugates demonstrated superior pharmacokinetics compared to radiolabeled trastuzumab without NGO, with more rapid clearance from the circulation. The use of NGO as a scaffold to build radiolabeled nano-immunoconstructs holds promise for molecular imaging of tumors.
authors.affiliation: CR-UK/MRC Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Oxford OX3 7LE, UK.
authors.forename: Bart
authors.initials: B
authors.lastname: Cornelissen
authors.forename: Sarah
authors.initials: S
authors.lastname: Able
authors.forename: Veerle
authors.initials: V
authors.lastname: Kersemans
authors.forename: Philip A
authors.initials: PA
authors.lastname: Waghorn
authors.forename: Sverre
authors.initials: S
authors.lastname: Myhra
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jurkshat
authors.forename: Alison
authors.initials: A
authors.lastname: Crossley
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Vallis
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000627:therapeutic use*; D010087:Oxides / Q000737:chemistry; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D006108:Graphite; D053769:Nanocapsules; D010087:Oxides; D004369:Pentetic Acid; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C109600:indium benzyldiethylenetriaminepentaacetic acid; C508053:ERBB2 protein, human