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In Vivo Targeting and Imaging of Tumor Vasculature with Radiolabeled, Antibody-Conjugated Nano-Graphene

Y Zhang

Y Zhang1*, K Yang2, H Hong1, J Engle1, L Feng2, C Theuer3, T Barnhart1, Z Liu2, W Cai1, (1) University of Wisconsin - Madison, Madison, WI, United States, (2) Soochow University, Suzhou, Jiangsu, China,(3) TRACON Pharmaceuticals, Inc., San Diego, CA, United States

WE-C-217BCD-6 Wednesday 10:30:00 AM - 12:30:00 PM Room: 217BCD

Purpose: Tour goal was to explore nano-graphene for in vivo tumor targeting and quantitatively evaluate the pharmacokinetics and tumor targeting efficacy through PET imaging, using 64Cu and 66Ga as the radiolabel.

Methods: Nano-graphene oxide (GO) sheets, with amino group-terminated PEG chains (10 kDa) covalently attached, were conjugated to NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid, a suitable chelator for 64Cu and 66Ga) and TRC105 (a mAb that binds to CD105, overexpressed on neovasculature). FACS analyses, size measurements, and serum stability studies were performed to characterize the GO conjugates before in vivo investigation (PET, biodistribution, blocking studies, etc.) in 4T1 murine breast tumor-bearing mice. Findings from imaging studies were then validated by histology.

Results: TRC105-conjugated GO, 20-30 nm in diameter, was specific for CD105 with little non-specific binding. Both 64Cu- and 66Ga- labled GO conjugates had excellent stability in mouse serum. Clearance of the GO conjugates in mice was via the hepatobiliary pathway. 64Cu/66Ga-NOTA-GO-TRC105 accumulated rapidly in the 4T1 tumor and tumor uptake remained stable over time (3.8±0.4, 4.5±0.4, 5.8±0.3, and 4.5±0.4 %ID/g at 0.5, 3, 7, and 24 h p.i. for 66Ga; 5.8±0.6, 5.3±0.6, 4.0±0.4, and 3.4±0.1 %ID/g at 0.5, 3, 24, and 48 h p.i. for 64Cu; n = 4). Blocking studies confirmed CD105 specificity of 64Cu/66Ga-NOTA-GOTRC105, which was corroborated by biodistribution studies. Furthermore, microscopy examination of GO in light view mode and immunofluorescence staining revealed that targeting of NOTA-GO-TRC105 is tumor vasculature CD105 specific with little extravasation.

Conclusions: For the first time, we demonstrated that GO can be specifically directed to the tumor neovasculature in vivo through targeting of CD105, a marker of tumor angiogenesis. The versatile chemistry of graphene-based nanomaterials makes them suitable nanoplatforms for future biomedical research, such as cancer theranostics.

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