RT Journal Article SR Electronic T1 The Role of Fibroblast Activation Protein in Glioblastoma and Gliosarcoma: A Comparison of Tissue, 68Ga-FAPI-46 PET Data, and Survival Data JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1217 OP 1223 DO 10.2967/jnumed.123.267151 VO 65 IS 8 A1 Oster, Christoph A1 Kessler, Lukas A1 Blau, Tobias A1 Keyvani, Kathy A1 Pabst, Kim M. A1 Fendler, Wolfgang P. A1 Fragoso Costa, Pedro A1 Lazaridis, Lazaros A1 Schmidt, Teresa A1 Feldheim, Jonas A1 Pierscianek, Daniela A1 Schildhaus, Hans Ulrich A1 Sure, Ulrich A1 Ahmadipour, Yahya A1 Kleinschnitz, Christoph A1 Guberina, Nika A1 Stuschke, Martin A1 Deuschl, Cornelius A1 Scheffler, Björn A1 Herrmann, Ken A1 Kebir, Sied A1 Glas, Martin YR 2024 UL http://jnm.snmjournals.org/content/65/8/1217.abstract AB Despite their unique histologic features, gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast activation protein (FAP) is a component of a tumor-specific subpopulation of fibroblasts that plays a critical role in tumor growth and invasion. Some case studies suggest an elevated expression of FAP in glioblastoma and a particularly strong expression in gliosarcoma attributed to traits of predominant mesenchymal differentiation. However, the prognostic impact of FAP and its diagnostic and therapeutic potential remain unclear. Here, we investigate the clinical relevance of FAP expression in gliosarcoma and glioblastoma and how it correlates with 68Ga–FAP inhibitor (FAPI)–46 PET uptake. Methods: Patients diagnosed with gliosarcoma or glioblastoma without sarcomatous differentiation with an overall survival of less than 2.5 y were enrolled. Histologic examination included immunohistochemistry and semiquantitative scoring of FAP (0–3, with higher values indicating stronger expression). Additionally, 68Ga-FAPI-46 PET scans were performed in a subset of glioblastomas without sarcomatous differentiation patients. The clinical SUVs were correlated with FAP expression levels in surgically derived tumor tissue and relevant prognostic factors. Results: Of the 61 patients who were enrolled, 13 of them had gliosarcoma. Immunohistochemistry revealed significantly more FAP in gliosarcomas than in glioblastomas without sarcomatous differentiation of tumor tissue (P < 0.0001). In the latter, FAP expression was confined to the perivascular space, whereas neoplastic cells additionally expressed FAP in gliosarcoma. A significant correlation of immunohistochemical FAP with SUVmean and SUVpeak of 68Ga-FAPI-46 PET indicates that clinical tracer uptake represents FAP expression of the tumor. Although gliosarcomas express higher levels of FAP than do glioblastomas without sarcomatous differentiation, overall survival does not significantly differ between the groups. Conclusion: The analysis reveals a significant correlation between SUVmean and SUVpeak in 68Ga-FAPI-46 PET and immunohistochemical FAP expression. This study indicates that FAP expression is much more abundant in the gliosarcoma subgroup of glioblastomas. This could open not only a diagnostic but also a therapeutic gap, since FAP could be explored as a theranostic target to enhance survival in a distinct subgroup of high-risk brain tumor patients with poor survival prognosis.