Abstract
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.
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Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
This study was supported by the National Natural Science Foundation of China (grant number 82001863) and the Shanghai Sailing Program (grant number 19YF1408200). We are grateful to the staff of the Department of Nuclear Medicine of Ruijin Hospital Affiliated to Shanghai Jiaotong University and to Wangxi Hai; Yang Liu and Yifan Zhang who contributed to the small-animal PET/CT imaging work.
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by ZX, YS, HY and JL. The first draft of the manuscript was written by JL and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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All authors (Zhan Xu, Yimeng Shi, Hongyan Yin, and Jing Lv) declare that they have no competing interests.
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All animal experiments were approved by the Institutional Review Board of Zhongshan Hospital, Fudan University, and were conducted in accordance with ethical principles governing animal welfare, rearing, and experimentation.
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Xu, Z., Shi, Y., Yin, H. et al. Preliminary study of a novel FAP-targeted ligand 68Ga-DOTA-FL in colon cancer imaging using small-animal PET/CT. Clin Transl Imaging 12, 91–97 (2024). https://doi.org/10.1007/s40336-023-00603-2
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DOI: https://doi.org/10.1007/s40336-023-00603-2