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Molecular Imaging and Biology

Open Access 17-05-2024 | Breast Cancer | Research Article

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

Authors: Aditi A. Shirke, Jing Wang, Gopolakrishnan Ramamurthy, Arpan Mahanty, Ethan Walker, Lifang Zhang, Abhiram Panigrahi, Xinning Wang, James P. Basilion

Published in: Molecular Imaging and Biology

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Abstract

Purpose

Prostate specific membrane antigen (PSMA) has been studied in human breast cancer (BCa) biopsies, however, lack of data on PSMA expression in mouse models impedes development of PSMA-targeted therapies, particularly in improving breast conserving surgery (BCS) margins. This study aimed to validate and characterize the expression of PSMA in murine BCa models, demonstrating that PSMA can be utilized to improve therapies and imaging techniques.

Methods

Murine triple negative breast cancer 4T1 cells, and human cell lines, MDA-MB-231, MDA-MB-468, implanted into the mammary fat pads of BALB/c mice, were imaged by our PSMA targeted theranostic agent, PSMA-1-Pc413, and tumor to background ratios (TBR) were calculated to validate selective uptake. Immunohistochemistry was used to correlate PSMA expression in relation to CD31, an endothelial cell biomarker highlighting neovasculature. PSMA expression was also quantified by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR).

Results

Accumulation of PSMA-1-Pc413 was observed in 4T1 primary tumors and associated metastases. Average TBR of 4T1 tumors were calculated to be greater than 1.5—ratio at which tumor tissues can be distinguished from normal structures—at peak accumulation with the signal intensity in 4T1 tumors comparable to that in high PSMA expressing PC3-pip tumors. Extraction of 4T1 tumors and lung metastases followed by RT-PCR analysis and PSMA-CD31 co-staining shows that PSMA is consistently localized on tumor neovasculature with no expression in tumor cells and surrounding normal tissues.

Conclusion

The selective uptake of PSMA-1-Pc413 in these cancer tissues as well as the characterization and validation of PSMA expression on neovasculature in this syngeneic 4T1 model emphasizes their potential for advancements in targeted therapies and imaging techniques for BCa. PSMA holds great promise as an oncogenic target for BCa and its associated metastases.
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Metadata
Title
Prostate Specific Membrane Antigen Expression in a Syngeneic Breast Cancer Mouse Model
Authors
Aditi A. Shirke
Jing Wang
Gopolakrishnan Ramamurthy
Arpan Mahanty
Ethan Walker
Lifang Zhang
Abhiram Panigrahi
Xinning Wang
James P. Basilion
Publication date
17-05-2024
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-024-01920-2