Prostate-specific membrane antigen (PSMA) as a potential target for molecular imaging and treatment in bone and soft tissue sarcomas
Fleur Kleiburg (University of Twente, Leiden University Medical Center)
Linda Heijmen (Leiden University Medical Center)
Hans Gelderblom (Leiden University Medical Center)
Szymon M. Kielbasa (Leiden University Medical Center)
Judith Vmg Bovée (Leiden University Medical Center)
Lioe Fee De Geus-Oei (Leiden University Medical Center, University of Twente, TU Delft - Applied Sciences)
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Abstract
Bone and soft tissue sarcomas are a group of rare malignant tumours with major histological and anatomical varieties. In a metastatic setting, sarcomas have a poor prognosis due to limited response rates to chemotherapy. Radioligand therapy targeting prostate-specific membrane antigen (PSMA) may offer a new perspective. PSMA is a type II transmembrane glycoprotein which is present in all prostatic tissue and overexpressed in prostate cancer. Despite the name, PSMA is not prostate-specific. PSMA expression is also found in a multitude of non-prostatic diseases including a subgroup of sarcomas, mostly in its neovascular endothelial cells. On PET/CT imaging, multiple sarcomas have also shown intense PSMA-tracer accumulation. PSMA expression and PSMA-tracer uptake seem to be highest in patients with aggressive and advanced sarcomas, who are also in highest need of new therapeutic options. Although these results provide a good rationale for the future use of PSMA-targeted radioligand therapy in a selection of sarcoma patients, more research is needed to gain insight into optimal patient selection methods, PSMA-targeting antibodies and tracers, administered doses of radioligand therapy, and their efficacy and tolerability. In this review, mRNA expression of the FOLH1 gene which encodes PSMA, PSMA immunohistochemistry, PSMA-targeted imaging and PSMA-targeted therapy in sarcomas will be discussed.
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