ImmunoPET for prostate cancer in the PSMA era: do we need other targets?

Introduction: In recent years, prostate specific membrane antigen (PSMA) has been gaining a crucial role for prostate cancer (PC) management, representing an ideal platform to combine diagnosis and therapy in a unique approach, namely theranostics. However, low or absent PSMA expression has been reported in up to 20% of PC cases. Our aim was to review the applications of PET/CT with radiolabeled antibodies (immunoPET) to identify biomarkers other than PSMA, potentially suitable for PC theranostics. Methods: We performed a Pubmed/Medline research to identify the most relevant findings of the literature published to date on this topic. Result: Prostate stem cell antigen (PSCA), a biomarker strongly overexpressed in metastatic castration-resistant PC (mCRPC), was effectively imaged in animal models through immunoPET with 124I and 89Zr-conjugated antibody fragments (minibodies) and gave promising results as a theranostic target in preliminary radioimmunotherapeutic applications. Delta-like ligand 3 (DLL3), a molecule associated with PC switching toward neuroendocrine differentiation, was also successfully imaged via immunoPET with 89Zr-labeled antibodies. Other biomarkers, among whom vascular endothelial growth factor receptor 2 (VEGFR-2) and CD46, were also investigated through immunoPET in pre-clinical studies. Conclusion: ImmunoPET pre-clinical studies have identified several biomarkers with potentially high impact on PC theranostics.