Tc-radiolabeled HER2 targeted exosome for tumor imaging.

Exosomes represent unique features including nontoxicity, non-immunogenicity, biodegradability, and targeting ability that make them suitable candidates for clinical applications. Therefore, in this study, Tc-radiolabel HER2 targeted exosomes (Tc-exosomes) were provided for tumor imaging. These exomes are obtained from genetically engineered cells and possessed DARPin G3 as a ligand for HER2 receptors. These exosomes were radiolabeled using fac-[Tc(CO)(HO)] synthon. The quality control showed high radiochemical purity (RCP) for Tc-exosomes (>96%). Tc-exosomes displayed a higher affinity toward SKOV-3 cells (higher HER2 expression) in comparison with MCF-7, HT29, U87-MG, A549 cell lines at different levels of HER2 expression. Trastuzumab (an antibody with a high affinity toward HER2) inhibited the binding of Tc-exosomes to SKOV-3 cells up to 40%. Biodistribution study in SKOV-3 tumor bearing nude mice confirmed the ability of Tc-exosomes for accumulation in the tumor. Tc-exosomes can visualize tumor in SKOV-3 tumor-bearing nude mouse. The blockage of HER2 receptors using trastuzumab (excessive amount) suggests the Tc-exosomes binding to the receptors and reduced the accumulation of Tc-exosomes in the tumor site. This suggest that Tc-exosomes interact with HER2 receptors and act through specific targeting.