Abstract LB038: Validation of FAPi PET biodistribution by immunohistochemistry in patients with solid cancers: a prospective exploratory study

• Published in: Cancer research (Chicago, Ill.) Ill.), 2021-07, Vol.81 (13_Supplement), p.LB038-LB038
• Main Authors: Mona, Christine E., Benz, Matthias, Hikmat, Firat, Grogan, Tristan G., Lueckerath, Katharina, Razmaria, Aria A., Riahi, Rana, Slavik, Roger, Grigis, Mark D., Carlucci, Giuseppe, Kelly, Kimberly A., Czernin, Johannes, Dawson, David W., Calais, Jeremie
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2021-LB038

Context: Fibroblast activation protein (FAP)-expressing cancer associated fibroblasts (CAFs), a major component of tumor stroma, confer treatment resistance, promote local progression, metastasis and immunosuppression. Because FAP is selectively expressed in the tumor stroma of many cancers, radiolabeled small molecule ligands targeting FAP are being explored for their use as pan-cancer theranostic agents. As a required step for further translation and approval by regulatory agencies FAPi PET imaging must be show to be a reliable biomarker of FAP expression in cancer and non-cancer tissues. The aim of the study is to define the incidence and degree of FAP expression by immunohistochemistry (IHC) across various cancers using Tissue Microarrays (TMAs) and to explore whether gallium-68 FAPi-46 PET image biodistribution faithfully reflects tumor FAP expression from resected tumor and non-tumor specimens. Methods: This was a prospective, exploratory, open-label, single-center imaging trial in cancer patients conducted in 2020. Patients scheduled to undergo surgical resection of the primary tumor and/or metastases were eligible. Patients underwent one whole body 68Ga-FAPI-46 PET/CT scan and subsequently underwent surgical resection of the primary tumor and/or metastasis. The primary endpoint measure was the Correlation of 68Ga-FAPI-46 PET maximum standardized uptake value (SUVmax) with FAP IHC score in cancer and non-cancer tissue. Results: The incidence of FAP expression in TMAs from 14 cancers ranged from 25 to 100% (mean 76.6± 25.3). 15 patients with the following cancer types were included: colorectal (n=4), head and neck (n=3), pancreas (n=2), breast (n=2), stomach (n=1), esophagus (n=2) and uterus (n=1). All 15 patients subsequently underwent surgery after the scan with a mean time interval of16.1 ± 14.4 days (range 1 - 50 days). Tumor resection was not attempted in 2 patients because unresectable. FAPI SUVmax and IHC score were higher in cancer tissue than in normal tissue: mean FAPI SUVmax 7.4±4.6 (range 1.5-15.9) vs 1.6±1.2 (range 0.4-5.1), (p