99mTc-Labeled RGD-Polyethylenimine Conjugates with Entrapped Gold Nanoparticles in the Cavities for Dual-Mode SPECT/CT Imaging of Hepatic Carcinoma.

We report the construction and characterization of 99mTc-labeled arginine-glycine-aspartic acid (RGD)-polyethylenimine (PEI) conjugates with entrapped gold nanoparticles in the cavities (RGD-99mTc-Au PENPs) for dual-mode single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of an orthotopic hepatic carcinoma model. In this study, PEI was successively decorated with diethylenetriaminepentaacetic acid, poly(ethylene glycol) (PEG), and PEGylated RGD segments, and was utilized as an effective nanoplatform to entrap Au NPs and to be labeled with 99mTc. We showed that the designed RGD-99mTc-Au PENPs displayed desirable colloidal stability and radiostability, and cytocompatibility in the investigated concentration range, and could be specifically uptaken by αvβ3 integrin-overexpressing liver cancer cells in vitro. In vivo CT and SPECT imaging results indicated that the particles were able to be accumulated within an orthotopic hepatic carcinoma and displayed both CT and SPECT contrast enhancement in the tumor tissue. With the proven biocompatibility in vivo via histological examinations, the designed RGD-99mTc-Au PENPs may be potentially employed as an effective nanoprobe for a highly efficient dual-mode SPECT/CT imaging of various αvβ3 integrin-overexpressing tumors.