Abstract
Our goal was to explore nano-graphene for in vivo tumor targeting and quantitatively evaluate the pharmacokinetics and tumor targeting efficacy through PET imaging, using (6 4) Cu and (66) Ga as the radiolabel. Nano-graphene oxide (GO) sheets, with amino group- terminated PEG chains (10 kDa) covalently attached, were conjugated to NOTA (l,4,7-triazacyclononane-l,4,7-triacetic acid, a suitable chelator for (6 4) Cu and (6 6) Ga) and TRC105 (a mAb that binds to CD 105, overexpressed on neovasculature). FACS analyses, size measurements, and serum stability studies were performed to characterize the GO conjugates before in vivo investigation (PET, bio distribution, blocking studies, etc.) in 4T1 murine breast tumor-bearing mice. Findings from imaging studies were then validated by histology. TRC105-conjugated GO, 20-30 nm in diameter, was specific for CD105 with little non-specific binding. Both (64) Cu- and (66) Ga- labled GO conjugates had excellent stability in mouse serum. Clearance of the GO conjugates in mice was via the hepatobiliary pathway. (v) Cu/(6 6) Ga-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. ...Continue Reading