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Updated: Aug 9, 2025
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Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
Fibroblast activation protein-targeted radionuclide therapy: background, opportunities, and challenges of first
Bastiaan M Privé1,2, Mohamed A Boussihmad3, Bart Timmermans3
1Department of Radiology and Nuclear Medicine, PO Box 9101, Radboudumc, 6500 HB, Nijmegen, The Netherlands. Bastiaan.prive@radboudumc.nl.
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.
Insights
Fibroblast activation protein (FAP) targeted radioligand therapy shows promise for treating advanced cancers. Early studies reveal effective responses and manageable side effects in patients, encouraging further research.
Area of Science:
- Oncology
- Radiochemistry
- Nuclear Medicine
Background:
- Fibroblast activation protein (FAP) is overexpressed in various cancer stromal tissues.
- FAP has long been considered a potential diagnostic and therapeutic cancer target.
- Radiolabeled FAP-targeting molecules offer a revolutionary approach to FAP-based cancer treatment.
Purpose of the Study:
- To review current preclinical and clinical data on FAP-targeted radioligand therapy (TRT).
- To discuss the potential of FAP TRT for broader clinical implementation.
- To identify FAP tracers used in TRT and summarize their reported outcomes.
Main Methods:
- A comprehensive PubMed search was conducted to identify all FAP tracers used for TRT.
- Included studies reported dosimetry, treatment response, or adverse events in preclinical and clinical settings.
- Clinical trial registries were searched for ongoing prospective FAP TRT trials.
Main Results:
- 35 papers related to FAP TRT were identified, including tracers like FAPI-04, FAPI-46, and FAP-2286.
- Data from over 100 patients treated with various FAP-targeted radionuclide therapies were reported.
- Objective responses were observed in advanced cancer patients with manageable adverse events.
Conclusions:
- FAP-targeted radioligand therapy demonstrates efficacy in difficult-to-treat, end-stage cancer patients.
- Early clinical data suggest manageable adverse events associated with FAP TRT.
- Further research and prospective trials are warranted to advance FAP TRT for broader clinical use.
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