Prostate Specific Membrane Antigen Expression in a Syngeneic Breast Cancer Mouse Model

Area of Science:

• Oncology
• Molecular Imaging
• Cancer Therapeutics

Background:

• Prostate specific membrane antigen (PSMA) has been investigated in human breast cancer (BCa).
• Limited data on PSMA expression in murine models hinders PSMA-targeted therapy development for BCa, especially for improving breast-conserving surgery (BCS) margins.

Purpose of the Study:

• To validate and characterize PSMA expression in murine BCa models.
• To demonstrate PSMA's utility in enhancing BCa therapies and imaging.

Main Methods:

• Imaged 4T1 murine and human BCa cell lines (MDA-MB-231, MDA-MB-468) using a PSMA-targeted agent (PSMA-1-Pc413).
• Calculated tumor-to-background ratios (TBR) to assess selective uptake.
• Used immunohistochemistry (IHC) for PSMA and CD31 (neovasculature marker) co-localization.
• Quantified PSMA expression via Reverse Transcriptase Polymerase Chain Reaction (RT-PCR).

Main Results:

• PSMA-1-Pc413 accumulated in 4T1 primary tumors and metastases with TBR > 1.5.
• PSMA expression was consistently localized on tumor neovasculature, not on tumor cells or normal tissues.
• RT-PCR and IHC confirmed PSMA presence on neovasculature in 4T1 models.

Conclusions:

• Selective uptake of PSMA-1-Pc413 and validated PSMA neovasculature expression in the 4T1 model show potential for BCa targeted therapies and imaging.
• PSMA is a promising oncogenic target for breast cancer and its metastases.