Fibroblast activation protein-targeted radionuclide therapy: background, opportunities, and challenges of first (pre)clinical studies

Bastiaan M Privé*, Mohamed A Boussihmad, Bart Timmermans, Willemijn A van Gemert, Steffie M B Peters, Yvonne H W Derks, Sanne A M van Lith, Niven Mehra, James Nagarajah, Sandra Heskamp, Harm Westdorp

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

28 Citations (Scopus)
216 Downloads (Pure)

Abstract

INTRODUCTION: Fibroblast activation protein (FAP) is highly overexpressed in stromal tissue of various cancers. While FAP has been recognized as a potential diagnostic or therapeutic cancer target for decades, the surge of radiolabeled FAP-targeting molecules has the potential to revolutionize its perspective. It is presently hypothesized that FAP targeted radioligand therapy (TRT) may become a novel treatment for various types of cancer. To date, several preclinical and case series have been reported on FAP TRT using varying compounds and showing effective and tolerant results in advanced cancer patients. Here, we review the current (pre)clinical data on FAP TRT and discuss its perspective towards broader clinical implementation. METHODS: A PubMed search was performed to identify all FAP tracers used for TRT. Both preclinical and clinical studies were included if they reported on dosimetry, treatment response or adverse events. The last search was performed on July 22 2022. In addition, a database search was performed on clinical trial registries (date 15th of July 2022) to search for prospective trials on FAP TRT.

RESULTS: In total, 35 papers were identified that were related to FAP TRT. This resulted in the inclusion of the following tracers for review: FAPI-04, FAPI-46, FAP-2286, SA.FAP, ND-bisFAPI, PNT6555, TEFAPI-06/07, FAPI-C12/C16, and FSDD.

CONCLUSION: To date, data was reported on more than 100 patients that were treated with different FAP targeted radionuclide therapies such as [177Lu]Lu-FAPI-04, [90Y]Y-FAPI-46, [177Lu]Lu-FAP-2286, [177Lu]Lu-DOTA.SA.FAPI and [177Lu]Lu-DOTAGA.(SA.FAPi)2. In these studies, FAP targeted radionuclide therapy has resulted in objective responses in difficult to treat end stage cancer patients with manageable adverse events. Although no prospective data is yet available, these early data encourages further research.

Original languageEnglish
Pages (from-to)1906-1918
Number of pages13
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume50
Issue number7
Early online date23 Feb 2023
DOIs
Publication statusPublished - Jun 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

Fingerprint

Dive into the research topics of 'Fibroblast activation protein-targeted radionuclide therapy: background, opportunities, and challenges of first (pre)clinical studies'. Together they form a unique fingerprint.

Cite this