P2, N=62, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

P2, N=48, Recruiting, European Organisation for Research and Treatment of Cancer - EORTC | Not yet recruiting --> Recruiting

P=N/A, N=107, Completed, Central Hospital, Nancy, France | Recruiting --> Completed

P2, N=30, Not yet recruiting, Stuthi Perimbeti

P1/2, N=90, Recruiting, C Ray Therapeutics | Not yet recruiting --> Recruiting

P3, N=670, Recruiting, AstraZeneca

P1, N=50, Recruiting, Full-Life Technologies GmbH | Trial completion date: Dec 2026 --> Sep 2027 | Trial primary completion date: Jun 2026 --> Oct 2026

The ENZA-p trial is a randomized phase 2 trial of enzalutamide versus enzalutamide ± lutetium-177 ([177Lu])Lu-PSMA-617 in mCRPC, which demonstrated a significant improvement in overall survival and quality of life with this combination compared to enzalutamide monotherapy [1,2]. Transational endpoints of the trial embedded at inception were designed to better understand the relationship between androgen blockade and PSMA expression and its potential impact on clinical outcomes. This mini-review will discuss the genetics of PSMA receptor expression, the preclinical evidence for androgen/PSMA receptor interaction, and the frequency, magnitude, and clinical significance of PSMA expression change in response to androgen blockade with enzalutamide.

Across heterogeneous and often heavily pretreated populations, lutetium-177 PSMA-617 demonstrated consistent clinical benefit, with a tolerable safety profile...Our mini review focuses on results in early-access programs. These findings support the effectiveness and manageable safety of RLT in routine practice, including in more complex cases that are often excluded from trials.

Theranostic research in nuclear medicine has expanded rapidly over the past two decades, with a trans-Atlantic and Asia-Pacific collaborative pattern. Current frontiers are shifting from beta-emitters toward alpha-emitters and tumor-microenvironment-targeted probes. Greater intercontinental cooperation and continued focus on novel radionuclides and under-explored targets may support future innovation and clinical translation.

To dissect the underlying mechanism, the authors performed high-resolution single-cell RNA sequencing of murine BM.HBOC treatment markedly expanded mature neutrophils, plasmacytoid dendritic cells, classical monocytes, natural killer T cells, and mature B cells, while concomitantly upregulating DNA damage repair genes such as Parp9, Dtx3l, and Smchd1 within these subsets. Gene set enrichment analysis confirmed significant activation of DNA damage response pathways, implying enhanced cellular radioresistance and improved tolerance to β-particle irradiation. Thus, HBOCs improve 177Lu-PSMA-617 antitumor efficacy indirectly via immune-subset expansion and DNA-repair reinforcement, offering a clinically feasible and safe strategy to optimize combination protocols for patients with mCRPC.

Our preliminary findings suggest that 1st cycle [¹⁷⁷Lu]Lu-PSMA-617 SPECT/CT semiquantitative parameters, especially when reflecting PSMA-expression, may serve as promising early predictors of the single-lesion response to RLT.