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

Fragomeni, Roberto A. Salas; Menke, Joshua; Holdhoff, Matthias; Ferrigno, C; Laterra, John; Solnes, Lilja B.; Javadi, Mehrbod S.; Szabó, Zsolt; Pomper, Martin G.; Rowe, Steven P.

doi:10.1097/rlu.0000000000001769

Cited by 57 publications

(48 citation statements)

References 7 publications

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“…Our data confirm the high intertumoral heterogeneity in gliomas and reveal tumor targets in subsets of gliomas that are associated with other cancer types, opening new avenues for targeted therapy. Our data confirm expression of the prostate cancer marker PSMA on microvasculature of glioblastoma, possibly providing opportunities for tumor-vascular targeting [55][56][57]. In a recent publication high expression levels of androgen receptor were described in glioblastomas, that actually translated into sensitivity to the AR antagonist enzalutamide [39].…”

Section: Discussionsupporting

confidence: 78%

Targeted RNA NextGenSeq profiling in oncology using single molecule molecular inversion probes

Lenting

et al. 2018

Preprint

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Hundreds of biology-based precision drugs are available that neutralize aberrant molecular pathways in cancer.Molecular heterogeneity and the lack of reliable companion diagnostic biomarkers for many drugs makes targeted treatment of cancer inaccurate for many individuals, leading to futile overtreatment. To acquire a comprehensive insight in aberrant actionable biological pathways in individual cancers we applied a costeffective targeted RNA next generation sequencing (NGS) technique. The test allows NGS-based measurement of transcript levels and splice variants of hundreds of genes with established roles in the biological behavior in many cancer types. We here present proof of concept that the technique generates a correct molecular diagnosis and a prognosis for glioma patients. The test not only confirmed known brain cancer-associated molecular aberrations but also identified aberrant expression levels of actionable genes and mutations that are associated with other cancer types. Targeted RNA-NGS is therefore a highly attractive method to guide precision therapy for the individual patient based on pathway analysis.

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Section: Discussionsupporting

confidence: 78%

Targeted RNA NextGenSeq profiling in oncology using single molecule molecular inversion probes

Lenting

et al. 2018

Preprint

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“…There are ample studies utilizing PSMA-based imaging agents for tumor detection in prostate cancer (24)(25)(26)(27)(28)(29)(30)(31), high-grade gliomas (32)(33)(34)(35)(36) and lung BMs (33), as well as in follicular thyroid adenoma (37), metastatic renal cell carcinoma (38) and in melanoma and small cell lung cancer (SCLC) xenografts in vivo (39). However, recent reports showed that the cerebral radionecrotic uptake (40) or stroke (41) resulted in false positive diagnoses of cerebral metastases based on PSMA/CT uptake as limitation of the PSMA-based diagnostic glioma imaging.…”

Section: Discussionmentioning

confidence: 99%

Prostate Specific Membrane Antigen expression in the vasculature of primary lung carcinomas associates with faster metastatic dissemination to brain

Ramanathan

Lehtipuro

Sihto

et al. 2019

Preprint

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Glioblastomas and brain metastases (BM) of solid tumors are the most common central nervous system neoplasms associated with very unfavorable prognosis. In this study, we report the association of Prostate Specific Membrane Antigen with various clinical parameters in a large cohort of primary and secondary brain tumors. A tissue micro array containing 371 cases of ascending grade gliomas pertaining to astrocytic origin, samples of 52 cases of primary lung carcinomas with matching brain metastases with follow-up time accounting to 10.4 years was evaluated for PSMA expression using immunohistochemistry. In addition, PSMA expression was studied in brain metastases arising from melanomas and breast carcinomas. Neovascular expression of PSMA was evident alongside with high expression in the proliferating microvasculature of glioblastomas when compared to the tumor cell expression. This result corroborated with the results obtained from the in silico (cancer genome databases) analyses. In the matched primary lung cancers and their brain metastases (n = 52), vascular PSMA expression in primary tumors led to significantly accelerated metastatic dissemination to the brain with a tendency towards poor overall survival. Taken together, we report the vascular expression of PSMA in the primary and secondary brain tumors that globally associates with the malignant progression and poor outcome of the patients.

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“…A correlation of PSMA expression between metastatic sites and primary tumors has been demonstrated in vivo and in vitro (18,20,21). Early human clinical studies demonstrated activity in breast tissue (22) and breast carcinoma using 111 In-J591 (23) planar imaging, as well as 68 Ga-PSMA-HBED-CC (N,N9-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N9-diacetic acid) PET/CT ( Fig. 1) (20,(23)(24)(25)(26).…”

Section: Breast Cancermentioning

confidence: 97%

“…Lung cancer is the second most common type of cancer in the United States, with over 220,000 new cases a year (14). Although 111 In-J591 (23); 68 Ga-HBED-CC (32,33) Colorectal adenocarcinoma no PSMA expression has been seen in normal lung tissue (2,8,15,16), tumor epithelial cells from various histologic types of lung cancer, as well as neovascular endothelial cells, have demonstrated PSMA expression (8,16,19,30). Furthermore, PSMA expression has been associated with higher histologic grades in non-small cell lung cancer (NSCLC) (31).…”

Section: Lung Cancermentioning

confidence: 99%

“…Furthermore, in vivo expression of PSMA in NSCLC has been demonstrated in primary tumors, lymph nodes, and bone metastasis with 111 In-J591 (23) planar imaging, as well as with 68 Ga-PSMA PET/CT (32,33). In one important study, the SUV max for NSCLC lesions was so high that they could not be reliably distinguished from prostate cancer lesions metastatic to the lung (33).…”

Section: Lung Cancermentioning

confidence: 99%

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Imaging of Nonprostate Cancers Using PSMA-Targeted Radiotracers: Rationale, Current State of the Field, and a Call to Arms

et al. 2018

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Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is highly overexpressed on prostate cancer epithelial cells and for which there is a growing body of literature examining the role of small-molecule and antibody radiotracers targeted against this protein for prostate cancer detection and therapy. Despite its name, PSMA is also expressed, to varying degrees, in the neovasculature of a wide variety of nonprostate cancers; indeed, the pathology literature is replete with promising immunohistochemistry findings. Several groups have begun to correlate those pathology-level results with in vivo imaging and therapy in nonprostate cancers using the same PSMA-targeted agents that have been so successful in prostate cancer. The potential to leverage radiotracers targeted to PSMA beyond prostate cancer is a promising approach for many cancers, and PSMA-targeted agents may be able to supplement or fill gaps left by other agents. However, to date, most of the reported findings with PSMA-targeted radiotracers in nonprostate malignancies have been in case reports and small case series, and the field must adopt a more thorough approach to the design and execution of larger prospective trials to realize the potential of these promising agents outside prostate cancer.

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

Cited by 57 publications

References 7 publications

Targeted RNA NextGenSeq profiling in oncology using single molecule molecular inversion probes

Targeted RNA NextGenSeq profiling in oncology using single molecule molecular inversion probes

Prostate Specific Membrane Antigen expression in the vasculature of primary lung carcinomas associates with faster metastatic dissemination to brain

Imaging of Nonprostate Cancers Using PSMA-Targeted Radiotracers: Rationale, Current State of the Field, and a Call to Arms

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