European urology focus · 2026
PSMA Therapy Grey Zones: Actinium, Lutetium, or Terbium for the Future of Radioligand therapy?
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Dragonetti Valentino, Mattana Francesco, Ceci Francesco
Аннотация
BACKGROUND: Radioligand therapy targeting the prostate-specific membrane antigen (PSMA) has been established as a key treatment for PSMA-positive metastatic castration-resistant prostate cancer following the approval of [177Lu]Lu-PSMA-617 (177Lu). However, variable responses, resistance, uncertain treatment sequencing, and limited efficacy in selected biological settings remain major clinical challenges. This narrative perspective reviews the rationale for radionuclide selection in PSMA-targeted therapy.
EVIDENCE ACQUISITION: A nonsystematic review of PubMed/MEDLINE and EMBASE was performed, updated to April 2026, prioritizing registered trials and multicenter studies.
EVIDENCE SYNTHESIS: 177Lu remains the clinical benchmark owing to randomized evidence, favorable logistics, posttherapy imaging, and a well-defined safety profile. Its β-emission crossfire effect is useful in bulky or heterogeneous disease but may be less effective against micrometastatic or PSMA-low/aggressive clones. Actinium-225-based targeted α-therapy offers high linear energy transfer radiation and may overcome β-emitter resistance, although side effects, imaging limitations, and supply constraints remain concerns. Terbium-161 (161Tb) may provide a valid alternative with potential advantages in small-volume disease.
CONCLUSIONS: Early data with 161Tb- and Lead-212-based PSMA therapies are promising but require prospective comparative validation. Future progress will depend on matching radionuclide properties to tumor biology rather than identifying a universally superior isotope.
EVIDENCE ACQUISITION: A nonsystematic review of PubMed/MEDLINE and EMBASE was performed, updated to April 2026, prioritizing registered trials and multicenter studies.
EVIDENCE SYNTHESIS: 177Lu remains the clinical benchmark owing to randomized evidence, favorable logistics, posttherapy imaging, and a well-defined safety profile. Its β-emission crossfire effect is useful in bulky or heterogeneous disease but may be less effective against micrometastatic or PSMA-low/aggressive clones. Actinium-225-based targeted α-therapy offers high linear energy transfer radiation and may overcome β-emitter resistance, although side effects, imaging limitations, and supply constraints remain concerns. Terbium-161 (161Tb) may provide a valid alternative with potential advantages in small-volume disease.
CONCLUSIONS: Early data with 161Tb- and Lead-212-based PSMA therapies are promising but require prospective comparative validation. Future progress will depend on matching radionuclide properties to tumor biology rather than identifying a universally superior isotope.