SNMMI: What Early Research Reveals About the Alpha-Emitting Radioconjugate ATNM-400 for Prostate Cancer

Preliminary study data with xenograft models indicate that the radioconjugate ATNM-400 may offer an emerging alternative to the PSMA-targeting radiotherapy ¹⁷⁷Lu-PSMA-617 and androgen receptor pathway inhibitors (ARPIs) for the treatment of prostate cancer (PCa), according to findings presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) conference.

In a low-PSMA expressing PCa preclinical model, researchers found that the monotherapy use of ATNM-400 40 μCi/kg (Actinium Pharmaceeuticals) offered 94.29 percent tumor growth inhibition (TGI) for the 22Rv1 PCa cell line. In contrast, the study authors noted a 5.12 percent TGI for ¹⁷⁷Lu-PSMA-617 40 mCi/kg monotherapy (Pluvicto, Novartis) and a 54.88 percent TGI for the combination of ¹⁷⁷Lu-PSMA-617 40 mCi/kg and enzalutamide 25 mg/kg/dy.

In comparative research with the second-generation ARPIs apalutamide 50 mg/kg/dy (Erleada, Johnson and Johnson) and darolutamide 100 mg/kg/dy (Nubeqa, Bayer), ATNM-400 40 μCi/kg provided superior TGI (94.3 percent) in contrast to 31.9 percent for apalutamide and 5.1 percent for darolutamide in treating a 22Rv1in vivo model. When researchers combined ATNM-400 40 μCi/kg with either ARPI, the researchers found that at least 57 percent of mice with tumors had a complete treatment response.

“ATNM-400 demonstrates superior and durable anti-tumor activity across PCa models resistant to approved ARPIs (enzalutamide, apalutamide and darolutamide) and PSMA-targeted radiotherapies … ,” noted lead study author Sumit Mukherjee, MS, PhD, a principal scientist and manager of in vivo biology for Actinium Pharmaceuticals, and colleagues.

(Editor’s note: For additional coverage from the SNMMI conference, click here.)

By triggering alpha particle-mediated double-stranded DNA (dsDNA) breaks and subsequent apoptosis of targeted tumor cells, the mechanism of action for ATNM-400 may create a legitimate option for addressing treatment resistance in patients with PCa, according to the researchers.

“By targeting a disease-driving, tumor-associated protein linked to progression and therapy resistance, ATNM-400 provides a mechanism-based strategy distinct from PSMA-directed and tumor microenvironment-targeted approaches,” added Mukherjee and colleagues.

(Editor’s note: For related content, see “What a New Study Reveals About Actinium-225 PSMA Therapy and Metastatic Castration-Resistant Prostate Cancer,” “The Reading Room Podcast: Emerging Trends with Theranostics in Prostate Cancer, Part 2” and “Current Perspectives on Prostate Cancer and Emerging Theranostic Agents, Part 1.”)

Reference

1. Mukherjee S, Peregrina K, Lewis D, et al. ATNM-400: a first-in-class non-PSMA actinium-225 antibody radioconjugate demonstrates superior efficacy to PSMA-617 radioligands and ARPIs with favorable safety profile in prostate cancer models. Presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) conference, May 30-June 2, 2026, Los Angeles.