Development of a fibroblast activation protein-targeted PET/NIR dual-modality probe and its application in head and neck cancer

Danni Li; Xuran Li; Jiaojiao Li; Yanhong Wang; Fei Tan; Xiao Li

doi:10.3389/fbioe.2023.1291824

Development of a fibroblast activation protein-targeted PET/NIR dual-modality probe and its application in head and neck cancer

Front Bioeng Biotechnol. 2023 Nov 3:11:1291824. doi: 10.3389/fbioe.2023.1291824. eCollection 2023.

Authors

Danni Li¹, Xuran Li¹, Jiaojiao Li¹, Yanhong Wang¹, Fei Tan^{1

2

3}, Xiao Li⁴

Affiliations

¹ Department of ORL-HNS, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
² The Royal College of Surgeons in Ireland, Dublin, Ireland.
³ The Royal College of Surgeons of England, London, United Kingdom.
⁴ Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China.

Abstract

Purpose: The combination of near-infrared (NIR) and positron emission tomography (PET) imaging presents an opportunity to utilize the benefits of dual-modality imaging for tumor visualization. Based on the observation that fibroblast activation protein (FAP) is upregulated in cancer-associated fibroblasts (CAFs) infiltrating all solid tumors, including head and neck squamous cell carcinoma (HNSCC), we developed the novel PET/NIR probe [⁶⁸Ga]Ga-FAP-2286-ICG. Preclinically, the specificity, biodistribution and diagnostic properties were evaluated. Methods: Cell uptake assays were completed with the U87MG cell to evaluate the specificity of the [⁶⁸Ga]Ga-FAP-2286-ICG. The tumor-targeting efficiency, biodistribution and optimal imaging time window of the [⁶⁸Ga]Ga-FAP-2286-ICG were studied in mice bearing U87MG xenografts. HNSCC tumor-bearing mice were used to evaluate the feasibility of [⁶⁸Ga]Ga-FAP-2286-ICG for tumor localization and guided surgical resection of HNSCC tumors. Results: The in vitro experiments confirmed that [⁶⁸Ga]Ga-FAP-2286-ICG showed good stability, specific targeting of the probe to FAP, and the durable retention effect in high-expressing FAP tumors U87MG cell. Good imaging properties such as good tumor uptake, high tumor-to-background ratios (5.44 ± 0.74) and specificity, and tumor contouring were confirmed in studies with mice bearing the U87MG xenograft. PET/CT imaging of the probe in head and neck cancer-bearing mice demonstrated specific uptake of the probe in the tumor with a clear background. Fluorescence imaging further validated the value of the probe in guiding surgical resection and achieving precise removal of the tumor and residual lesions. Conclusion: In a preclinical model, these attractive [⁶⁸Ga]Ga-FAP-2286-ICG PET/NIR imaging acquired in head and neck cancer make it a promising FAP-targeted multimodal probe for clinical translation.

Keywords: ICG; PET; dual-modality imaging; fibroblast activation protein; head and neck cancer; optical imaging.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work is sponsored by the Fundamental Research Funds for the Central Universities. It was also supported by the National Natural Science Foundation of China (No. 82271192).