RT Journal Article SR Electronic T1 Correlation of 68Ga-FAPi-46 PET biodistribution with FAP expression by immunohistochemistry in patients with solid cancers: a prospective translational exploratory study JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.121.262426 DO 10.2967/jnumed.121.262426 A1 Christine E. Mona A1 Matthias R. Benz A1 Firas Hikmat A1 Tristan R. Grogan A1 Katharina Lückerath A1 Aria Razmaria A1 Rana Riahi A1 Roger Slavik A1 Mark D. Girgis A1 Giuseppe Carlucci A1 Kimberly A. Kelly A1 Samuel W French A1 Johannes Czernin A1 David W. Dawson A1 Jeremie Calais YR 2021 UL http://jnm.snmjournals.org/content/early/2021/11/04/jnumed.121.262426.abstract AB 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.