Novel alpha radiopharmaceutical therapy shows promise in early-phase prostate cancer trial

by Society of Nuclear Medicine and Molecular Imaging

edited by Sadie Harley, reviewed by Andrew Zinin

Sadie Harley

Scientific Editor

Meet our editorial team
Behind our editorial process

Andrew Zinin

Chief Editor

Meet our editorial team
Behind our editorial process Editors' notes

This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:

fact-checked

peer-reviewed publication

trusted source

proofread

The GIST Add to Preferred Sources

A new alpha-emitting radiopharmaceutical therapy (RPT) for advanced prostate cancer was well tolerated, with no dose-limiting toxicities observed, and showed encouraging signs of antitumor activity, according to a trial published in The Journal of Nuclear Medicine's Late-Breaking Fast Track.

Among patients treated with ²¹²Pb-ADVC001, 80% experienced a decline in prostate-specific antigen (PSA) levels of at least 50%, and the overall response rate was 100%. The findings support further clinical development of ²¹²Pb-ADVC001 to address the unmet needs in metastatic prostate cancer.

Prostate-specific membrane antigen (PSMA)–targeted RPT is an established treatment for metastatic androgen pathway modulation-resistant prostate cancer (mAPM-R, formerly metastatic castration-resistant prostate cancer). Although ¹⁷⁷Lu-PSMA-617, a beta-emitting RPT, has shown improved overall and radiographic progression-free survival in pivotal trials, approximately one-third of patients are resistant to ¹⁷⁷Lu-PSMA, and most responders progress during or soon after treatment.

"Current RPTs use fixed dosing regimens that do not account for variability in tumor response," said the study authors. "These limitations highlight the need for novel treatment strategies that may enhance patient outcomes using more potent payloads and optimization of dose and schedule."

Alpha-emitting RPTs have emerged as a new treatment approach: unlike beta emitters such as ¹⁷⁷Lu, which release lower-energy particles that travel up to a couple of millimeters, alpha emitters release high-energy particles that travel only a few cell widths, delivering concentrated radiation to cancer cells while sparing surrounding healthy tissue.

The TheraPb Phase I trial, a first-in-human study, evaluated both escalating doses and dosing frequency of the alpha-targeting RPT ²¹²Pb-ADVC001.

The study included 22 participants with progressive mAPM-R previously treated with an androgen-receptor pathway inhibitor and taxane chemotherapy. Escalating doses of 60–200 MBq of ²¹²Pb-ADVC001 were administered at prespecified intervals every six, four, two or one week for up to six doses across seven dose-schedule cohorts.

Researchers examined dose-limiting toxicities and adverse events to recommend doses for a Phase II trial. They also evaluated PSA response, radiographic progression-free survival and overall response rate.

No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached. The most common treatment-related adverse events were dry mouth and nausea, and no serious adverse events occurred. Given these findings, the study committee selected 160 and 200 MBq as the recommended doses for Phase II of TheraPb.

In this early-phase study, 80% of participants had a PSA decline of 50% or more, and the median radiographic progression-free survival was 11.2 months. The overall response rate was 100%.

"Flexibility in dosing, together with the overall safety profile of ²¹²Pb-ADVC001, further provides a rationale for evaluating combination strategies with other anticancer agents to maximize clinical outcomes," stated the authors.

Publication details

Aaron R. Hansen et al., TheraPb Phase 1b: First-in-Human Dose-Escalation and Optimization Study of ²¹²Pb-ADVC001 in PSMA-Positive Metastatic Androgen Pathway Modulation–Resistant Prostate Cancer, Journal of Nuclear Medicine (2026). DOI: 10.2967/jnumed.126.274089

Journal information: Journal of Nuclear Medicine

Clinical categories

OncologyUrologyClinical pharmacologyMen's health Provided by Society of Nuclear Medicine and Molecular Imaging Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Andrew Zinin

Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →

Citation: Novel alpha radiopharmaceutical therapy shows promise in early-phase prostate cancer trial (2026, October 27) retrieved 28 October 2026 from https://medicalxpress.com/news/2026-10-alpha-radiopharmaceutical-therapy-early-phase.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.