Lutetium-177 radiopharmaceuticals in cancer care: progress and challenges.

Lutetium-177 (177Lu)-based Radioligand Therapy (RLT) has emerged as an important modality in precision oncology, with demonstrated clinical benefit in selected malignancies. Its clinical relevance is underscored by regulatory approvals of Lutathera® for neuroendocrine tumours and Pluvicto® for metastatic castration-resistant prostate cancer. However, despite these advances, the field faces significant challenges that limit broader clinical translation and optimisation. In this review, we provide a critical and balanced evaluation of the current 177Lu RLT landscape, integrating evidence from clinical trials, emerging targets, and translational studies. We highlight that much of the existing evidence is derived from small, non-randomised studies with inherent risk of bias, limiting the strength of clinical conclusions. Key challenges include the lack of standardised and clinically actionable dosimetry, insufficient predictive biomarkers beyond target expression, vulnerability of isotope supply chains, and the development of drug-evasive traits in malignant cells. In addition, heterogeneity in trial design and limited long-term safety data further constrain clinical implementation. We propose a strategic roadmap to advance 177Lu RLT toward a more rigorous, reproducible, and equitable precision oncology framework, emphasising the transition from empiric application to evidence-based personalisation.