Highlights related to radioligand therapies

In this video, Dr Willem Lybaert, medical oncologist at the VITAZ hospital and the University Hospital Antwerp, and Prof Christophe Deroose, nuclear medicine specialist at the University Hospitals Leuven, reflect on the growing prominence of radioligand therapy in oncology. Radioligand therapy is rapidly evolving into a central treatment modality, fueled by recent clinical trial successes and substantial pharmaceutical investment.

The interest in radioligand therapy was evident at ESMO, where well-attended, dedicated sessions emphasized its expanding application beyond neuroendocrine tumors (NETs). This rise in visibility marks a shift from niche to mainstream, beginning with foundational trials such as NETTER-1 in NETs and the VISION trial in metastatic castration-resistant prostate cancer. These studies established proof of concept and regulatory approval for lutetium-based radiopharmaceuticals and PSMA-targeted agents.

Recent developments are moving the field toward earlier lines of therapy. The COMPETE and NETTER-2 trials, for example, demonstrated promising results for lutetium-labeled somatostatin analogues in earlier settings, including in first line. In prostate cancer, the LUNAR study extended the potential of lutetium-177 PSMA therapies. Particularly striking were findings from LUNAR, in which radioligand therapy combined with stereotactic radiotherapy prolonged the progression-free interval from 8 to 18 months in hormone-sensitive oligometastatic disease, underscoring its ability to target micrometastatic lesions beyond the visual detection of PSMA PET scans.1

In parallel, alpha-emitting radiopharmaceuticals, notably 212Pb-based agents, offer higher-potency cytotoxicity with limited tissue penetration, theoretically improving tumor-specific targeting. Early-phase trials of 212Pb-dotamtate demonstrated robust efficacy and durable disease control, with a 72% progression-free rate at 36 months in treatment-naïve, GEP-NET patients. However, safety concerns emerged, including grade 3 renal toxicity and unexpected dysphagia, highlighting the need for careful compound selection and monitoring.2

Overall, radioligand therapy is shifting from a late-line to potentially earlier intervention, supported by tolerable quality-of-life profiles and the option to combine it with systemic agents. Its integration into routine care demands strong multidisciplinary collaboration, particularly in tumor boards, to optimize timing, patient selection, and sequencing. As platforms for targeting continue to expand and long-term data mature, radioligand therapy is poised to become a cornerstone across multiple tumor types in the coming decade.