In Vivo Interrogation of Cell-Penetrating Peptide Function: Accumulation in Tumors and the Potential as a Specific PET Probe

体内研究细胞穿透肽的功能:在肿瘤中的积累及其作为特异性PET探针的潜力

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作者:Zhan Si ,Lulu Tian ,Hongxin Zhou ,Jiasheng Lin ,Jun Zhou

Abstract

We aimed to evaluate the biodistribution and specificity of 68Ga-DOTA-TAT and RHO-TAT using MGC-803 and HT-29 tumor cells as well as tumor-xenografted nude mice and to demonstrate its application in positron emission tomography (PET) imaging. The in vitro evaluation of 68Ga-DOTA-TAT was assessed in MGC-803 and HT-29 cell lines, and the in vivo evaluation of 68Ga-DOTA-TAT was also performed in mice bearing MGC-803 or HT-29 tumors, respectively. Fluorescence microscopy was also employed to evaluate the specificity of RHO-TAT in vitro in MGC-803 and HT-29 cells as well as ex vivo in tumor slices of the corresponding tumor models. The in vivo imaging differences between 68Ga-DOTA-TAT and 18F-FDG in MGC-803 and HT-29 tumors were also studied. The biodistribution and micro-PET results demonstrated significant uptake of 68Ga-DOTA-TAT in non-FDG-avid MGC-803 tumors, whereas there was negligible uptake in FDG-avid HT-29 tumors. RHO-TAT showed superior fluorescence microscopy imaging effects in MGC-803 cells and tumor slices but not in HT-29 cells and tumor slices, which were consistent with the in vivo results. 68Ga-DOTA-TAT combined with 18F-FDG can be applied noninvasively in cancers with PET imaging for potential patient selection and stratification. We demonstrated a higher binding of 68Ga-DOTA-TAT and RHO-TAT to MGC-803 cells as well as to non-FDG-avid MGC-803 xenografted tumors and a lower binding to HT-29 cells and FDG-avid xenografted tumors. These results suggest that TAT has the potential to be a ligand for targeting certain tumors.

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