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 I-124 and Zr-89-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 Zr-89-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.

Automated summary

Prostate specific membrane antigen (PSMA) plays a crucial role in prostate cancer management, but it is absent or lowly expressed in some cases. ImmunoPET imaging has identified new biomarkers, such as PSCA and DLL3, which show promise as potential targets for therapy and diagnosis. Other biomarkers, including VEGFR-2 and CD46, have also been explored through immunoPET in pre-clinical studies. These immunoPET pre-clinical studies have high impact on the development of prostate cancer theranostics.