Researchers have unveiled promising early results for a novel experimental drug, ATNM-400, designed to combat advanced prostate cancer with a powerful, highly targeted radiation payload. Presented at the recent American Association for Cancer Research (AACR) Annual Meeting, the preclinical findings suggest this approach could offer a potent new weapon against metastatic castration-resistant prostate cancer (mCRPC).
Therapies like Pluvicto, which targets the PSMA protein with beta radiation, have offered hope but face challenges due to varying PSMA levels on tumors and the nature of beta radiation.
ATNM-400 takes a different, potentially more powerful approach. It’s an antibody radioconjugate (ARC). An antibody component is designed to seek out and bind to a specific protein found in high amounts on the surface of mCRPC cells (a target where previous antibody-based drugs have failed).
Attached to this antibody is Actinium-225 (Ac-225), a radioactive isotope that emits highly potent alpha particles.
Alpha particles deliver a strong burst of energy over a very short distance, minimizing collateral damage to nearby healthy tissues. This is the first time an Ac-225 ARC has been developed against this specific mCRPC target.

In laboratory and animal model studies, ATNM-400 demonstrated impressive performance. It was created with high purity and showed it could rapidly bind to and enter prostate cancer cells. Once inside, it proved highly effective at killing these cells in a dose-dependent manner.
Crucially, when tested in mouse models of human prostate cancer, ATNM-400 showed it could selectively accumulate in tumors and remain there for up to six days, while largely clearing from healthy organs. Imaging confirmed this targeted delivery. A single dose of ATNM-400 led to significant tumor growth inhibition – reducing tumor size by nearly 70% at a lower dose and almost completely (99.8%) at a higher dose, all while being well-tolerated by the animals. E
arly safety assessments based on these studies suggest a potentially acceptable safety profile for human trials. Researchers are also actively testing ATNM-400 in models resistant to Pluvicto, with results expected soon.

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