P=N/A, N=300, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

Lutetium-177-PSMA-617 has become the standard radioligand therapy for metastatic castration-resistant prostate cancer, whereas alpha-emitting agents remain under clinical investigation...Integrative models combining imaging, genomic, and liquid biopsy data pave the way toward precision oncology and personalized therapeutic decision-making. Advances in imaging and theragnostics are reshaping prostate cancer management, bridging the gap between molecular biology and clinical practice to enable precision oncology.

P1, N=14, Completed, The Netherlands Cancer Institute | N=24 --> 14 | Recruiting --> Completed

P1, N=6, Active, not recruiting, Emory University | Recruiting --> Active, not recruiting | N=10 --> 6

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.

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