Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases

Abstract

BackgroundPrimary and secondary brain cancers are highly treatment resistant, and their marked angiogenesis attracts interest as a potential therapeutic target. Recent observations reveal that the microvascular endothelium of primary high-grade gliomas expresses prostate specific membrane antigen (PSMA). Breast cancers express PSMA and they frequently form secondary brain tumors. Hence we report here our pilot study addressing the feasibility of PSMA targeting in brain and metastatic breast tumors, by examining PSMA levels in all glioma grades (19 patients) and in breast cancer brain metastases (5 patients).MethodsTumor specimens were acquired from archival material and normal brain tissues from autopsies. Tissue were stained and probed for PSMA, and the expression levels imaged and quantified using automated hardware and software. PSMA staining intensities of glioma subtypes, breast tumors, and breast tumor brain metastases were compared statistically versus normals.ResultsNormal brain microvessels (4 autopsies) did not stain for PSMA, while a small proportion (<5%) of healthy neurons stained, and were surrounded by an intact blood brain barrier. Tumor microvessels of the highly angiogenic grade IV gliomas showed intense PSMA staining which varied between patients and was significantly higher (p < 0.05) than normal brain. Grade I gliomas showed moderate vessel staining, while grade II and III gliomas had no vessel staining, but a few (<2%) of the tumor cells stained. Both primary breast cancer tissues and the associated brain metastases exhibited vascular PSMA staining, although the intensity of staining was generally less for the metastatic lesions.ConclusionsOur results align with and extend previous data showing PSMA expression in blood vessels of gliomas and breast cancer brain metastases. These results provide a rationale for more comprehensive studies to explore PSMA targeted agents for treating secondary brain tumors with PSMA expressing vasculature. Moreover, given that PSMA participates in angiogenesis, cell signaling, tumor survival, and invasion, characterizing its expression may help guide later investigations of the poorly understood process of low grade glioma progression to glioblastoma.

Prostate-Specific Membrane Antigen–Targeted Imaging With [18F]DCFPyL in High-Grade Gliomas

“…Regardless, the tumor-to-normal tissue uptake ratio was superb for a diagnostic imaging modality. Our histological findings also correlate to previously published data where PSMA expression has been seen in tumor cells of lower-grade gliomas, 5 whereas the expression for GBM has been mostly in the tumor neovasculature [5][6][7] with an exception. 8 As a conclusion, we found [ 18 F]DCFPyL binds PSMA in the neovasculature of GBM and in tumor cells of anaplastic astrocytoma.…”

68Ga-PSMA imaging of metastatic breast cancer

“…Recently it has been demonstrated to accumulate in metastatic clear-cell renal cell carcinoma [3] and interestingly several studies have provided evidence that PSMA is also expressed in the tumour-associated vasculature of primary breast cancers and distant metastases [4,5].We report the case of a 33-year-old woman with metastatic breast carcinoma who underwent 68 Ga-PSMA and 18 F-FDG PET/CT imaging for restaging and evaluation of the most appropriate therapeutic option. Images demonstrated intense and extensive skeletal uptake in the axial and appendicular skeleton with liver metastases.…”

Radiotracers Used in Nuclear Medicine for Prostate Cancer Diagnosis and Follow-Up

“…In malignant tissues, PSMA has been shown to be strongly expressed in the stroma adjacent to the neo-vasculature of multiple solid tumors [12][13][14][15] . In PC, overexpression is associated with tumor grade, aneuploidy, and biochemical recurrence.…”