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Fibroblast activation protein is overexpressed by cancer-associated fibroblasts (CAFs) in the stroma of several tumor entities and provides anti-immunogenic effects [1]. It can be targeted with radiolabeled small-molecule inhibitors (FAPIs) [2].
This image demonstrates a patient with progression of lung metastatic, fibrous spindle cell soft tissue sarcoma. Primary tumor located between bladder and rectum as well as early generations of oligo-focal metastases had previously been treated by resection and external-beam radiotherapy. In systemic stage, mutanom-based vaccination [3], cyclophosphamide, and pazopanib had already been used but the patient was considered inappropriate for standard chemotherapy with anthracyclines. An interdisciplinary tumor conference considered experimental FAPI-RLT a promising option for this therapy-refractory patient to serve as a “can opener” for succeeding immunotherapy.
FAPI-PET/CT demonstrated target positive tumor phenotype (a). Due to the relatively short biological tumor half-life of quinoline-based FAPI-46 [1], it was labeled with short physical half-life (46.3 h) 153Sm. Emission scans during therapy demonstrate tumor targeting up to 44 h p.i. and rapid clearance from normal organs (b). Three cycles with cumulative 20 GBq 153Sm- and 8GBq Y-90-FAPI-46 (153Sm was not available with sufficiently high specific activity) were well tolerated and achieved stable disease for 8 months (c). Next treatment lines were pembrolizumab, experimentally enhanced with oncolytic parvovirus [4], and nab-paclitaxel. Under both therapies, the patient progressed after only 3 months.
One explanation for the clinical activity of 90Y/153Sm-FAPI-46 in this particular case might be FAP expression in both CAFs and sarcoma tumor cells [5], which is unfortunately not the case in other tumor entities. Of course, one case is no proof of general efficacy but obviously this image encourages further studies of FAPI-RLT against soft tissue sarcoma. However, due to technical issues related to 153Sm, e.g., regarding specific activity and contamination with 154Eu, additional short physical half-life isotopes should be evaluated as alternative options.
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References
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TL, UH, CK, and FLG have a patent application for FAPI-ligands. TL, UH, CK, and FLG also hold shares of a consultancy for iTheranostics.
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Kratochwil, C., Giesel, F.L., Rathke, H. et al. [153Sm]Samarium-labeled FAPI-46 radioligand therapy in a patient with lung metastases of a sarcoma. Eur J Nucl Med Mol Imaging 48, 3011–3013 (2021). https://doi.org/10.1007/s00259-021-05273-8
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DOI: https://doi.org/10.1007/s00259-021-05273-8