P1, N=80, Recruiting, ARTBIO Inc. | Trial completion date: Sep 2033 --> Nov 2028

P2, N=110, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2028 --> Apr 2026

Total cell-bound activity, rather than added activity, better predicted radiotoxicity in both TP53-wild-type and TP53-null cell lines, indicating that its therapeutic effect is primarily governed by PSMA-mediated uptake rather than p53 status. These results support the therapeutic potential of [212Pb]Pb-AB001 across cells with varying TP53 status and suggest that combining [212Pb]Pb-AB001 with DNA repair or checkpoint inhibitors may enhance treatment efficacy.

By situating PSMA within this broader biomarker landscape, we outline opportunities for theranostic integration, including predictive models, combination therapies and expansion into non-prostate malignancies. Understanding the biology of PSMA in conjunction with novel biomarkers provides a framework for optimising theranostic applications and advancing personalised cancer care.

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.

P1/2, N=123, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

BiTEs, such as pasotuxizumab for prostate cancer, and CD3×B7-H3 BiTE for bladder cancer, demonstrate potential in overcoming the limitations of traditional therapies and immune checkpoint inhibitors...Combination therapies with immune checkpoint inhibitors and oncolytic viruses, as well as advancements in BiTE technology, are essential to improving treatment efficacy. The future of BiTEs in uro-oncology lies in overcoming current limitations, optimising therapeutic strategies, and expanding clinical trials to solidify their role in cancer immunotherapy.

P1/2, N=52, Active, not recruiting, Inovio Pharmaceuticals | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=40, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

BsAbs are a promising therapeutic strategy for mCRPC, with potential to improve outcomes in this poorly treatable disease. Addressing challenges (toxicity, tumor microenvironment, response durability) via research and trials is key to unlocking their full potential. Future research should focus on optimizing constructs, exploring novel targets, and developing combination therapies to advance BsAbs in prostate cancer.

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.

P1, N=80, Recruiting, ARTBIO Inc. | Trial primary completion date: Sep 2033 --> Nov 2027