Preliminary study of a novel FAP-targeted ligand 68Ga-DOTA-FL in colon cancer imaging using small-animal PET/CT

Purpose

This study explored the feasibility of ⁶⁸gallium (Ga)-labeled novel fibroblast activation protein (FAP)-targeted ligand for tumor imaging through small-animal PET/CT (positron emission computed tomography/computed tomography).

Methods

The FAP-ligand (FL) was created by adding the chelating group dodecane tetraacetic acid (DOTA) and labeling with ⁶⁸Ga. The MC38 cell line was used to establish a C57BL/6 mice colon cancer model. The radioactivity distribution of labeled ⁶⁸Ga-DOTA-FL across various organs of the mouse model was examined ex-vivo. In addition, ⁶⁸Ga-DOTA-FL tumor-targeted imaging in vivo was performed using small-animal PET/CT. Finally, western blotting and immunofluorescence imaging of MC38 cells and xenotransplant tumor tissues were conducted.

Results

The radiolabeling rate and radiochemical purity of ⁶⁸Ga-DOTA-FL were above 95%. Both western blotting and immunofluorescence imaging revealed FAP expression in the tumor tissues, but not in the MC38 cells. Small-animal PET/CT imaging indicated that the tumor imaging was clearest at 30 min after ⁶⁸Ga-DOTA-FL treatment. Examination of the radioactivity distribution in vitro revealed that at 30 min after the ⁶⁸Ga-DOTA-FL treatment, the target/non-target ratio for tumor and muscle tissue was 4.0 ± 0.3 (n = 3).

Conclusions

⁶⁸Ga-DOTA-FL can be used for the specific tumor imaging in mouse models, which might provide a novel alternative for FAP-targeted tumor imaging.