P1, N=29, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Jun 2026 | Trial primary completion date: Oct 2025 --> Jun 2026

The tumor-to-bone marrow absorbed dose ratio was in the same range for [161Tb]Tb-DOTA-LM3 as for [177Lu]Lu-DOTATOC. The administration of 1 GBq of [161Tb]Tb-DOTA-LM3 was safe for all patients, without relevant adverse events.

Although radioiodine provides the historical foundations of theranostics, the prototype RLTs include 68Ga-DOTATATE and 177Lu-DOTATATE, which target somatostatin receptor subtype 2 in neuroendocrine tumors, and 68Ga-PSMA-617 and 177Lu-PSMA-617, which target prostate cancer. RLT, weaponized in cancer management through advances in instrumentation and radiochemistry, is transforming the nuclear oncology landscape. Equitable access to these advanced tools remains a global consideration.

Clinically approved agents, such as 177Lu-DOTATATE and 177Lu-PSMA-617, are used for neuroendocrine tumors and metastatic castration-resistant prostate cancer, respectively, with significant therapeutic efficacy. The potential avenues include theranostics, predictive modeling for patient selection, and new molecular targeting strategies. This review highlights the transformative potential of RPhs in precision oncology, providing an overview of the current clinical applications and future research trajectories toward improved cancer management.

In 2018, the Food and Drug Administration (FDA) approved lutetium-177 (177Lu) DOTATATE (LUTATHERA, Advanced Accelerator Applications [Novartis]) for the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs)...Less than 5 years later, in March 2022, 177Lu vipivotide tetraxetan (PLUVICTO, Advanced Accelerator Applications) received FDA approval for the treatment of prostatespecific membrane antigen-positive castration-resistant metastatic prostate cancer...As more radiotheranostic agents and applications get adopted in clinical practice, interventional radiologists are likely to get exposed to this field in a way or another. In this article, we discuss the fundamentals of radiotheranostic therapy and explore the expanding role interventional radiology (IR) is expected to play as an essential partner in modern oncology practice.

P1, N=27, Recruiting, Imperial College London | Trial completion date: Dec 2025 --> Feb 2029 | Trial primary completion date: Dec 2025 --> Jun 2026

Following PRRT, analysis of [68Ga]Ga-FAPI-04 PET/CT in well-differentiated NET is important to avoid misinterpretation. Benign fibrosis following treatment may show FAPI uptake as a possible source of false-positive findings on [68Ga]Ga-FAPI-04 PET/CT in the evaluation of NET.

Given the lack of significant effects on direct DNA repair or transcriptomic responses, our findings suggest that HSP90 inhibition radiosensitizes NET cells by inducing a pleiotropic effect on multiple stress-related pathways at the protein level, rather than solely through disruption of DNA damage response mechanisms. This effect is likely driven by loss of HSP90 function and subsequent cumulated unfolded protein and proteotoxic stress.

Baseline assessment reflects the patient's reserves and their post-PRRT state. Further, women are more prone to BM-related toxicity from PRRT. These insights can help optimize treatment strategies and improve patient outcomes in this population.

P2, N=153, Not yet recruiting, RTOG Foundation, Inc. | Initiation date: Aug 2025 --> Nov 2025

Two RLT agents, [177Lu]Lu-DOTA-TATE (Lutathera®) and [177Lu]Lu-PSMA-617 (Pluvicto®), have received regulatory approval for the treatment of advanced gastroenteropancreatic neuroendocrine tumours and metastatic castration-resistant prostate cancer, respectively. Finally, we outline the main clinical challenges, including fixed dosing regimens, resistance, toxicity, and variability in patient selection and response assessment. Continued research to optimise radiopharmaceutical design, together with investment in infrastructure, workforce capacity, and international collaboration, will be essential to expand access and realise the full potential of RLT as a leading treatment strategy in modern oncology.

Short-course corticosteroid prophylaxis to prevent tumor flare reactions in high-risk patients with neuroendocrine tumors treated with 177Lu-DOTATATE did not appear to decrease the incidence of tumor flare reactions compared to previously reported numbers. Randomized, placebo-controlled trials looking at the use of corticosteroids to prevent tumor flare reactions in patients treated with 177Lu-DOTATATE are needed to fully elucidate the safety and efficacy of corticosteroids used in this setting and to determine the impact on treatment outcomes.