Construction and Evaluation of the Tumor-Targeting, Cell-Penetrating Multifunctional Molecular Probe iCREKA

Abstract EN

A novel tumor stroma targeting and membrane-penetrating cyclic peptide, named iCREKA, was designed and labeled by fluorescein isothiocyanate (FITC) and positron emitter 18F to build the tumor-targeting tracers.

The FITC-iCREKA was proved to have significantly higher cellular uptake in the glioma U87 cells in the presence of activated MMP-2 than that in absence of activated MMP-2 by cells fluorescence test in vitro.

The tumor tissue fluorescence microscope imaging demonstrated that FITC-iCREKA accumulated in the walls of the blood vessels and the surrounding stroma in the glioma tumor at 1 h after intravenous injection.

While at 3 h after injection, FITC-iCREKA was found to be uptaken in the tumor cells.

However, the control FITC-CREKA can only be found in the tumor stroma, not in the tumor cells, no matter at 1 h or 3 h after injection.

The whole-animal fluorescence imaging showed that the glioma tumor could be visualized clearly with high fluorescence signal.

The microPET/CT imaging further demonstrated that 18F-iCREKA could target U87MG tumor in vivo from 30 min to 2 h after injection.

The present study indicated the iCREKA had the capacity of tumor stroma targeting and the membrane-penetrating.

It was potential to be developed as the fluorescent and PET tracers for tumor imaging.