PSMA Theranostics for Prostate Cancer: Evidence, Pitfalls, and Implementation in Japan.
Authors
Affiliations (5)
Affiliations (5)
- Department of Diagnostic Imaging, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
- Department of Nuclear Medicine, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.
- Department of Nuclear Medicine, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
- Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.
- Department of Radiology, Graduate School of Medicine, University of the Ryukyus, Ginowan, Okinawa, Japan.
Abstract
Prostate-specific membrane antigen (PSMA) is a Type II transmembrane glycoprotein markedly overexpressed on prostate cancer cells, enabling a single molecular target to support both positron emission tomography (PET) imaging and targeted radionuclide therapy. Over the past decade, PSMA-PET/CT has been incorporated into international guidelines for primary staging of high-risk prostate cancer and for biochemical recurrence, with the landmark proPSMA trial establishing its diagnostic superiority over conventional imaging; whether PSMA-PET-guided management improves long-term oncologic outcomes, however, remains an open question addressable only by prospective PSMA-specific trials. On the therapeutic side, <sup>177</sup>Lu-PSMA-617 has become a standard treatment option for metastatic castration-resistant prostate cancer (mCRPC) after androgen-receptor pathway inhibitor (ARPI) and taxane chemotherapy, and is moving into earlier lines of disease. Alpha-emitting and next-generation ligands, together with quantitative whole-body imaging and artificial intelligence, are redefining both patient selection and response assessment, although randomized evidence for many of these approaches remains limited. In Japan, the concurrent 2025 approval of <sup>177</sup>Lu-vipivotide tetraxetan and its companion PSMA diagnostic has initiated a national roll-out that will depend on a hub-and-spoke framework of regional PSMA-PET centers and therapy spokes, a prepared nuclear medicine workforce, and domestic registries to refine Japanese-specific evidence. This review summarizes the current clinical evidence for PSMA-PET/CT and <sup>177</sup>Lu-PSMA radioligand therapy, highlights interpretive and implementation pitfalls, and outlines practical priorities for the Japanese clinical and academic community.