(P 176) FIBROBLAST ACTIVATION PROTEIN ALPHA AS THERANOSTIC TARGET IN SARCOMA

Author(s)

Rainer Hamacher, MD

Medical Oncologist
Department of Medical Oncology, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany

Co-Author(s)

LK

Lukas Kessler, MD

Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
PC

Phyllis F. Cheung, PhD

Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
CH

Christoph E. Heilig, MD

Clinician Scientist
Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ)
Heidelberg, Baden-Wurttemberg, Germany
IM

Ilektra A. Mavroeidi, MD

Resident doctor
Department of Medical Oncology, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
Helena Lanzafame, MD (she/her/hers)

Researcher
Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
Kim M. Pabst, MD

Physician in training
Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
NH

Nader Hirmas, MD, ScD

Doctoral candidate
Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
JH

Jennifer Hüllein, PhD

Computational Oncology, Molecular Precision Oncology Program, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT) Heidelberg
Heidelberg, Baden-Wurttemberg, Germany
SL

Sven-Thorsten Liffers, PhD

Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
SB

Sabrina Borchert, PhD

Institute of Pathology, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
PF

Pedro Fragoso Costa, M.Sc.

Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
JF

Justin Ferdinandus, MD

Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
KK

Karina Kostbade, MD

Department of Medical Oncology, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
Johanna Falkenhorst, MD (she/her/hers)

Dr. med.
Department of Medical Oncology, Sarcoma Center, West German Cancer Center, University Duisburg-Essen, Medical School, Essen, Germany
Essen, Nordrhein-Westfalen, Germany
MA

Marit Ahrens, MD

Attending, Hematology/Oncology
Medical Clinic II, University Hospital Frankfurt
Frankfurt am Main, Hessen, Germany
HG

Hanno Glimm, MD

Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ)
Dresden, Sachsen, Germany
LU

Lale Umutlu, MD

Department of Diagnostic and Interventional Radiology and Neuroradiology, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
MS

Martin Schuler, MD

Department of Medical Oncology, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
DH

Daniel Hübschmann, PhD

Computational Oncology, Molecular Precision Oncology Program, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT) Heidelberg
Heidelberg, Baden-Wurttemberg, Germany
Sebastian Bauer, MD (he/him/his)

Director Sarcoma Center
Department of Medical Oncology, Sarcoma Center, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen and German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
Essen, Nordrhein-Westfalen, Germany
SF

Stefan Fröhling, MD (he/him/his)

Division Head
Division of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ)
Heidelberg, Baden-Wurttemberg, Germany
KH

Ken Herrmann, MD

Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
JS

Jens T. Siveke, MD

Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
HS

Hans-Ulrich Schildhaus, MD

Institute of Pathology, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany
WF

Wolfgang P. Fendler, MD

Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen
Essen, Nordrhein-Westfalen, Germany

Objective: Fibroblast activation protein alpha (FAP) is expressed by several malignant solid tumors. At this, FAP-targeted radioligands are emerging as promising diagnostic and therapeutic (theranostic) approaches. Here, we aim to: 1) characterize FAP RNA and protein expression in sarcoma subtypes; and 2) report on PET imaging and subsequent radioligand therapy (RLT) in bone and soft-tissue sarcomas using FAPI, a theranostic ligand for FAP.

Methods: We investigated [68Ga]Ga-FAPI PET uptake as well as mRNA and protein expression in different subtypes of sarcoma. Tracer uptake in tumor lesions was quantified by SUVmax. Correlation between SUVmax and FAP staining was analyzed. Moreover, we report findings for RLT with [90Y]Y-labelled FAPI-46 ([90Y]Y-FAPI-46) in sarcoma patients who had (a) progressive metastatic disease, (b) exhaustion of approved therapies, and whose tumors had (c) high FAP expression, defined as SUVmax ≥10 in more than 50% of tumor lesions.

Results: Within the FAPI-PET prospective observational trial (NCT04571086), we investigated 144 patients with sarcoma so far. Most subtypes demonstrated [68Ga]Ga-FAPI uptake in PET, with highest uptake in solitary fibrous tumor (SFT). In a cohort of 47 patients with sarcoma, we observed a significant correlation between [68Ga]Ga-FAPI-PET uptake intensity and histopathological FAP-expression (Spearman’s r = 0.43; p = 0.03) [1]. In the NCT MASTER cohort, FAP mRNA expression could be detected in all investigated sarcoma subtypes (N = 631 patients), and the highest median expression was found in SFT samples. Notably, in an independent cohort of SFT patients (N=38) FAP protein expression was observed in N=30 (79%) with intermediate to high expression (>10% positive cells) in N=25 (66%), particularly in tumor cells.
So far, 21 patients were found eligible for receiving [90Y]Y-FAPI-46 RLT under compassionate access, and among which, the majority had sarcoma (76%, N=16: SFT N=9, and N=1 for each of: fibrosarcoma, gastrointestinal neuroectodermal tumor, conventional chondrosarcoma, osteosarcoma, chordoma, undifferentiated sarcoma, uterine leiomyosarcoma). Disease control after RLT was noted in 7/12 (58%) patients with sarcoma versus 1/4 (25%) of patients with other solid tumors.

Conclusion: FAP is an attractive diagnostic and therapeutic target in sarcoma. We confirm an association of tumoral FAPI-PET uptake intensity and histopathological FAP expression in sarcoma patients. The high FAP expression, frequently in tumor cells, makes sarcoma, especially SFT patients, predestinated for FAP-targeted RLT with promising therapeutic efficacy. Prospective trials on the diagnostic and therapeutic use of FAP-directed radioligands are required.

Reference
[1] Kessler L, Ferdinandus J, Hirmas N, Bauer S, Dirksen U, Zarrad F, et al. Ga-68-FAPI as diagnostic tool in sarcoma: Data from the FAPI-PET prospective observational trial. J Nucl Med. 2021.