Abstract
Purpose: Fibroblast activation protein (FAP)-expressing cancer-associated fibroblasts confer treatment resistance, promote metastasis and immunosuppression. Because FAP is overexpressed in many cancers, radiolabeled molecules targeting FAP are studied for their use as pan-cancer theranostic agents. This study aims to establish the spectrum of FAP expression across various cancers by immunohistochemistry and to explore whether gallium-68 FAPi-46 (68Ga-FAPi-46) PET biodistribution faithfully reflects FAP expression from resected cancer and non-cancer specimens. Methods: We conducted a FAP expression screening by using immunohistochemistry on a pan-cancer human tissue microarray (TMA) (141 patients, 14 different types of cancer) and an interim analysis of a prospective exploratory imaging trial in cancer patients. Volunteer patients underwent one whole body 68Ga-FAPi-46 PET/CT scan and subsequently, surgical resection of their primary tumor and/or metastasis. 68Ga-FAPi-46 PET maximum standardized uptake value (SUVmax and SUVmean) was correlated with FAP immunohistochemistry score in cancer and non-cancer tissues for each patient. Results: FAP was expressed across all 14 cancers types on TMA with variable intensity and frequency, ranging from 25 to 100% (mean 76.6±25.3%). Strong FAP expression was observed in 50-100% of cancers of the bile duct, bladder, colon, esophagus, stomach, lung, oropharynx, ovary and pancreas. Fifteen patients with various cancer types (colorectal (n = 4), head and neck (n = 3), pancreas (n = 2), breast (n = 2), stomach (n = 1), esophagus (n = 2) and uterus (n = 1)) underwent surgery following their 68Ga-FAPi-46 PET/CT scan within a mean time interval of 16.1±14.4 days. 68Ga-FAPi-46 SUVs and immunohistochemistry scores were higher in cancer than in normal tissue: mean SUVmax 7.7 vs 1.6 (p<0.001), mean SUVmean 6.2 vs 1.0 (p<0.001) and mean FAP immunohistochemistry score 2.8 vs 0.9 (p<0.001). FAP immunohistochemistry scores strongly correlated with 68Ga-FAPi 46 SUVmax and SUVmean: r=0.781 (95%CI 0.376-0.936; p<0.001) and r=0.783 (95%CI 0.379-0.936; p<0.001), respectively. Conclusion: In this interim analysis of a prospective exploratory imaging trial, 68Ga-FAPi-46 PET biodistribution across multiple cancers strongly correlated with FAP tissue expression. These findings support further exploration of FAPi PET as a pan-cancer imaging biomarker for FAP expression and stratification tool for FAP- targeted therapies.
- Immunoassay
- Molecular Imaging
- PET/CT
- 68Ga-FAPi-46
- Fibroblast Activation Protein
- Immunohistochemistry
- PET/CT
- Pan-Cancer
Footnotes
Immediate Open Access: Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications. License: https://creativecommons.org/licenses/by/4.0/. Details: https://jnm.snmjournals.org/page/permissions.
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