P2, N=33, Recruiting, City of Hope Medical Center | Trial completion date: Oct 2027 --> Oct 2029 | Trial primary completion date: Oct 2027 --> Oct 2029

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.

P2, N=118, Not yet recruiting, New Approaches to Neuroblastoma Therapy Consortium

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

P2, N=35, Recruiting, Institut Curie | Not yet recruiting --> Recruiting

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

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.