Annotating STEAP1 regulation in prostate cancer with 89Zr immuno-PET

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Therapeutic antibodies targeting STEAP1 are in development for castration-resistant prostate cancer (PCa).
• STEAP1 regulation in PCa is complex, influenced by the androgen receptor (AR) and present in AR-null tumors.
• Accurate diagnostic strategies are needed to guide STEAP1-targeted therapies in PCa patients.

Purpose of the Study:

• To develop and evaluate (89)Zr-labeled MSTP2109A ((89)Zr-2109A), a PET radiotracer for imaging STEAP1.
• To assess the utility of (89)Zr-2109A in preclinical PCa models for detecting STEAP1 expression and treatment-induced changes.

Main Methods:

• Preparation and preclinical evaluation of (89)Zr-2109A, a radiotracer based on a humanized anti-STEAP1 antibody.
• Utilized PET imaging in human PCa xenograft models (CWR22Pc, 22Rv1, PC3) to assess tracer localization and sensitivity.

Main Results:

• (89)Zr-2109A demonstrated specific localization in STEAP1-positive PCa models.
• The tracer sensitively detected significant (∼66%) decreases in STEAP1 expression in response to treatment in an AR-dependent model (CWR22PC).

Conclusions:

• Immuno-PET with (89)Zr-2109A can effectively detect dynamic changes in STEAP1 expression.
• Further clinical investigation of (89)Zr-2109A in PCa patients is warranted to optimize the use of STEAP1-targeted therapies.