Prostate- specific membrane antigen (PSMA) as a potential target for molecular imaging and treatment in bone and soft tissue sarcomas

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 PSMAtargeted therapy in sarcomas will be discussed.