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

IF 3 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Molecular Imaging and Biology Pub Date : 2024-08-01 Epub Date: 2024-05-17 DOI:10.1007/s11307-024-01920-2

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

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引用次数: 0

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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前列腺特异性膜抗原在合成乳腺癌小鼠模型中的表达

目的：已对人类乳腺癌（BCa）活检组织中的前列腺特异性膜抗原（PSMA）进行了研究，然而，小鼠模型中 PSMA 表达数据的缺乏阻碍了 PSMA 靶向疗法的开发，尤其是在改善保乳手术（BCS）切缘方面。本研究旨在验证和描述 PSMA 在小鼠 BCa 模型中的表达，证明 PSMA 可用于改进疗法和成像技术：将小鼠三阴性乳腺癌 4T1 细胞和人类细胞系 MDA-MB-231、MDA-MB-468 植入 BALB/c 小鼠的乳腺脂肪垫，用我们的 PSMA 靶向治疗剂 PSMA-1-Pc413 进行成像，计算肿瘤与背景比 (TBR) 以验证选择性摄取。免疫组化法将 PSMA 的表达与 CD31（一种突显新血管的内皮细胞生物标记物）相关联。PSMA的表达也通过逆转录酶聚合酶链反应（RT-PCR）进行量化：结果：PSMA-1-Pc413在4T1原发肿瘤和相关转移瘤中聚集。经计算，4T1肿瘤的平均TBR大于1.5--这是肿瘤组织与正常结构的区分比率--达到积累峰值时，4T1肿瘤的信号强度与高PSMA表达的PC3-pip肿瘤相当。对 4T1 肿瘤和肺转移瘤进行提取，然后进行 RT-PCR 分析和 PSMA-CD31 联合染色，结果表明 PSMA 始终定位于肿瘤新生血管，在肿瘤细胞和周围正常组织中没有表达：结论：PSMA-1-Pc413在这些癌症组织中的选择性摄取以及PSMA在4T1合成模型中肿瘤新生血管上表达的特征和验证强调了它们在BCa靶向治疗和成像技术方面的发展潜力。PSMA有望成为BCa及其相关转移瘤的致癌靶点。

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.