Three Targets Beyond PSMA in Prostate Cancer Radioligand Therapy

Radioligand therapy transformed advanced prostate cancer care with PSMA targeting. Now experts eye options for PSMA-resistant or low-expression cases. At APCCC 2026, Dr. Ken Herrmann named ACP3, B7-H3, and STEAP1/STEAP2 as top priorities. These could reach patients (outside clinical trials) in four to five years.

ACP3, or prostatic acid phosphatase, binds tighter than PSMA in some tumors. Diagnostic tracers already show uptake where PSMA fails and stay bound for days, not hours. Therapeutic versions enter first-in-human trials in 2026. ACP3 tracers light up tumors clearly while sparing healthy salivary glands and kidneys.

B7-H3 drives tumor aggression across prostate cancer types, including neuroendocrine. It acts like PD-L1 but suits radioligands well. We can learn a lot from how B7-H3 antibody-drug conjugates are advancing rapidly, those successes now translate directly into clean radioligand imaging with minimal off-target effects and recent IND filings.

STEAP1 and STEAP2 mark cell surfaces in aggressive disease. Bispecifics like xaluritamig are already in Phase 3, proving these targets work. That ADC and bispecific progress paves the way for radioligand versions showing strong tumor signals without gland uptake, now entering patient trials.

These targets expand options for metastatic castration-resistant prostate cancer. Trials accelerate in 2026, promising radiation straight to tough tumors.

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