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. 2020 May 30:148:105312.
doi: 10.1016/j.ejps.2020.105312. Epub 2020 Mar 17.

99mTc-radiolabeled HER2 targeted exosome for tumor imaging

Sajjad Molavipordanjani  1 , Shabanali Khodashenas  2 , Seyed Mohammad Abedi  3 , Mehdi Forouzandeh Moghadam  4 , Alireza Mardanshahi  5 , Seyed Jalal Hosseinimehr  6
Affiliations

99mTc-radiolabeled HER2 targeted exosome for tumor imaging

Sajjad Molavipordanjani et al. Eur J Pharm Sci. .

Abstract

Exosomes represent unique features including nontoxicity, non-immunogenicity, biodegradability, and targeting ability that make them suitable candidates for clinical applications. Therefore, in this study, 99mTc-radiolabel HER2 targeted exosomes (99mTc-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-[99mTc(CO)3(H2O)3]+ synthon. The quality control showed high radiochemical purity (RCP) for 99mTc-exosomes (>96%). 99mTc-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 99mTc-exosomes to SKOV-3 cells up to 40%. Biodistribution study in SKOV-3 tumor bearing nude mice confirmed the ability of 99mTc-exosomes for accumulation in the tumor. 99mTc-exosomes can visualize tumor in SKOV-3 tumor-bearing nude mouse. The blockage of HER2 receptors using trastuzumab (excessive amount) suggests the 99mTc-exosomes binding to the receptors and reduced the accumulation of 99mTc-exosomes in the tumor site. This suggest that 99mTc-exosomes interact with HER2 receptors and act through specific targeting.

Keywords: (99m)Tc; HER2; Radiolabeling; Tumor targeting; exosome.

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