(UroToday.com) The 2026 PSMA & Beyond conference featured a developing novel radioligands session and presentation by Dr. Wolfgang Fendler discussing the pro stance for the future of FAP. Fibroblast Activation Protein (FAP) is a serine protease that is highly expressed on reactive stroma fibroblasts and sarcoma (highest expression in sarcomas and gastrointestinal tumors), providing a potentially ideal target for FAP-directed theranostics:
In 2025, Dr. Fendler and colleauges published a phase 2 trial assessing the positive predictive value of [68Ga]Ga-FAPI-46 PET for detecting FAP-expressing tumors and the potential association between PET radiotracer uptake intensity and immunohistochemical FAP expression. Among 158 eligible participants, the patient-based positive predictive value of [68Ga]Ga-FAPI-46 PET for detecting FAP-positive tumors based on immunohistochemical FAP staining was 90% (95% CI 84-95) and region-based positive predictive value was 92% (95% CI 85-96) in 127 (88%) of 144 participants with histopathological validation:
90Y-FAPI-46 radioligand therapy has also shown disease control for sarcoma patients in a 30 patient trial whereby 77 cycles of 90Y-FAPI-46 were administered. The overall disease control rate was 48%, with one patient having a partial response. Tolerability was excellent with only 2 (6%) grade 3+ anemia, and 3 (10%) grade 3+ thrombocytopenia. Other agents of 90Y are also being used, which Dr. Fendler presented as part of unpublished data.
In an effort to optimize radiation, Thera4Care is performing the first prospective, first in human assessment (EU HORIZON) phase 1b trial of 161Terbium-FAPI dimer treatment. This will compare 90Y-FAPI dimer versus 161Tb-FAPI dimer:
Finally, Dr. Fendler discussed several next generation FAP radioligands. 177Lu-PNT3090 prolongs tumor retention and FAMI-mFS provides covalent binding:
Additionally, 177Lu-OncoFAP-23 provides trimeric binding and 177Lu-/225Ac-RTX2358 has trifunctional alpha and beta activity:
Dr. Fendler concluded his presentation discussing the pro stance for the future of FAP with the following take-home points:
- Sarcoma and hepatobiliary/gastrointestinal tumors demonstrate high FAP expression and are favorable candidates
- The FAPI PET prospective trial met its primary endpoint: biomarker of FAP + high positive predictive value
- Preliminary FAP radioligand therapy demonstrates favorable safety and leads to disease stabilization or regression
- Next generation ligands improve tumor targeting
Presented by: Wolfgang Fendler, MD, University Hospital Essen, Essen, Germany
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2026 PSMA & Beyond Conference, Los Angeles, CA, Thurs, Mar 26 – Fri, Mar 27, 2026.
References:
- Pabst KM, Weber MM, Laschinsky C, et al. [68Ga]Ga-FAPI-46 PET accuracy for cancer imaging with histopathology validation: A single-centre, single-arm, interventional, phase 2 trial. Lancet Oncol. 2025 Sep;26(9):1204-1214.