Fibroblast Activation Protein α-Directed Imaging and Therapy of Solitary Fibrous Tumor

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Rainer Hamacher - , LVR-Universitätsklinik Essen (Autor:in)
  • Kim M Pabst - , Universitätsklinikum Essen (Autor:in)
  • Phyllis F Cheung - , LVR-Universitätsklinik Essen (Autor:in)
  • Christoph E Heilig - , Nationales Zentrum für Tumorerkrankungen (NCT) Heidelberg (Autor:in)
  • Jennifer Hüllein - , Nationales Zentrum für Tumorerkrankungen (NCT) Heidelberg (Autor:in)
  • Sven-Thorsten Liffers - , LVR-Universitätsklinik Essen (Autor:in)
  • Sabrina Borchert - , Universitätsklinikum Essen (Autor:in)
  • Pedro Fragoso Costa - , Universitätsklinikum Essen (Autor:in)
  • Benedikt M Schaarschmidt - , Universitätsklinikum Essen (Autor:in)
  • Lukas Kessler - , Universitätsklinikum Essen (Autor:in)
  • Monika A Miera - , LVR-Universitätsklinik Essen (Autor:in)
  • Margret Droste - , LVR-Universitätsklinik Essen (Autor:in)
  • Merve Akbulut - , LVR-Universitätsklinik Essen (Autor:in)
  • Johanna Falkenhorst - , LVR-Universitätsklinik Essen (Autor:in)
  • Fadi Zarrad - , Universitätsklinikum Essen (Autor:in)
  • Karina Kostbade - , LVR-Universitätsklinik Essen (Autor:in)
  • Ilektra A Mavroeidi - , LVR-Universitätsklinik Essen (Autor:in)
  • Hanno Glimm - , Nationales Centrum für Tumorerkrankungen (Partner: UKD, MFD, HZDR, DKFZ), Deutsches Konsortium für Translationale Krebsforschung (Partner: DKTK, DKFZ), Deutsches Krebsforschungszentrum (DKFZ), Helmholtz-Zentrum Dresden-Rossendorf, Universitätsklinikum Carl Gustav Carus Dresden, Deutsches Konsortium für Translationale Krebsforschung (DKTK) - Heidelberg (Autor:in)
  • Lale Umutlu - , Universitätsklinikum Essen (Autor:in)
  • Martin Schuler - , LVR-Universitätsklinik Essen (Autor:in)
  • Daniel Hübschmann - , Deutsches Konsortium für Translationale Krebsforschung (DKTK) - Heidelberg (Autor:in)
  • Sebastian Bauer - , LVR-Universitätsklinik Essen (Autor:in)
  • Stefan Fröhling - , Nationales Zentrum für Tumorerkrankungen (NCT) Heidelberg (Autor:in)
  • Ken Herrmann - , Universitätsklinikum Essen (Autor:in)
  • Jens T Siveke - , LVR-Universitätsklinik Essen (Autor:in)
  • Hans-Ulrich Schildhaus - , Universitätsklinikum Essen (Autor:in)
  • Wolfgang P Fendler - , Universitätsklinikum Essen (Autor:in)

Abstract

Fibroblast activation protein α (FAPα) is expressed at high levels in several types of tumors. Here, we report the expression pattern of FAPα in solitary fibrous tumor (SFT) and its potential use as a radiotheranostic target. Methods: We analyzed FAPα messenger RNA and protein expression in biopsy samples from SFT patients using immunohistochemistry and multiplexed immunofluorescence. Tracer uptake and detection efficacy were assessed in patients undergoing clinical 68Ga-FAPα inhibitor (FAPI)-46 PET,18F-FDG PET, and contrast-enhanced CT. 90Y-FAPI-46 radioligand therapy was offered to eligible patients with progressive SFT. Results: Among 813 patients and 126 tumor entities analyzed from the prospective observational MASTER program of the German Cancer Consortium, SFT (n = 34) had the highest median FAPα messenger RNA expression. Protein expression was confirmed in tumor biopsies from 29 of 38 SFT patients (76%) in an independent cohort. Most cases showed intermediate to high FAPα expression by immunohistochemistry (24/38 samples, 63%), which was located primarily on the tumor cell surface. Nineteen patients who underwent 68Ga-FAPI-46 PET imaging demonstrated significantly increased tumor uptake, with an SUVmax of 13.2 (interquartile range [IQR], 10.2), and an improved mean detection efficacy of 94.5% (SEM, 4.2%), as compared with 18F-FDG PET (SUVmax, 3.2 [IQR, 3.1]; detection efficacy, 77.3% [SEM, 5.5%]). Eleven patients received a total of 34 cycles (median, 3 cycles [IQR, 2 cycles]) of 90Y-FAPI-46 radioligand therapy, which resulted in disease control in 9 patients (82%). Median progression-free survival was 227 d (IQR, 220 d). Conclusion: FAPα is highly expressed by SFT and may serve as a target for imaging and therapy. Further studies are warranted to define the role of FAPα-directed theranostics in the care of SFT patients.

Details

OriginalspracheEnglisch
Seiten (von - bis)252-257
Seitenumfang6
FachzeitschriftJournal of Nuclear Medicine
Jahrgang65
Ausgabenummer2
Frühes Online-Datum4 Jan. 2024
PublikationsstatusVeröffentlicht - Apr. 2024
Peer-Review-StatusJa

Externe IDs

Mendeley 991fc449-5745-3dc4-92f9-2a22a36aafc1
unpaywall 10.2967/jnumed.123.266411
Scopus 85184282421

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Membrane Proteins, Positron Emission Tomography Computed Tomography, Quinolines, Solitary Fibrous Tumors, Humans, Gallium Radioisotopes, Fluorodeoxyglucose F18, Positron-Emission Tomography, Endopeptidases, RNA, Messenger