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

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Abstract

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.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Santa Maria Goretti Hospital, Via Canova 3, 04100, Latina, Italy

    Luca Filippi

  2. Nuclear Medicine Unit, Department of Medicine (DIMED), University of Padua, Via Giustiniani 2, 35128, Padua, Italy

    Laura Evangelista

  3. Department of Nuclear Medicine, University of Pretoria, Pretoria, 0001, South Africa

    Mike M. Sathekge

  4. Nuclear Medicine Research Infrastructure (NuMeRI), Steve Biko Academic Hospital, Pretoria, 001, South Africa

    Mike M. Sathekge

  5. Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy

    Orazio Schillaci

  6. IRCCS Neuromed, Pozzilli, Italy

    Orazio Schillaci

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  1. Luca Filippi
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  2. Laura Evangelista
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  3. Mike M. Sathekge
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  4. Orazio Schillaci
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All the authors equally contributed to conception and design of the article, or acquisition, analysis and interpretation of data; L.F. and L.E. wrote the initial draft of the manuscript; M.M.S. and O.S. critically revised the manuscript for important intellectual content.

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Correspondence to Luca Filippi.

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Filippi, L., Evangelista, L., Sathekge, M.M. et al. ImmunoPET for prostate cancer in the PSMA era: do we need other targets?. Clin Transl Imaging 10, 587–596 (2022). https://doi.org/10.1007/s40336-022-00520-w

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