Expression of the gastrin‐releasing peptide receptor, the prostate stem cell antigen and the prostate‐specific membrane antigen in lymph node and bone metastases of prostate cancer

Ananias, H. J. K.; Heuvel, Marius C. van den; Helfrich, Wijnand; Jong, Igle J. de

doi:10.1002/pros.20957

Cited by 143 publications

(115 citation statements)

References 49 publications

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“…Other authors also reported a high sensitivity of 85-100% in lymph node and distant metastases. 30,31 Until a few years ago, detection of TMPRSS2-ERG fusion was only possible using fluorescence in situ hybridization. Since TMPRSS2-ERG fusion highly correlates with ERG overexpression, the newly available monoclonal antibodies displaying ERG overexpression open up the opportunity for routine utilization.…”

Section: Discussionmentioning

confidence: 99%

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Queisser¹,

Hagedorn²,

Braun³

et al. 2015

Modern Pathology

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Prostate cancer is mostly diagnosed at an early stage; however, some tumors are diagnosed in a metastatic stage as cancer of unknown primary origin. In order to allow specific treatment in the case of prostate cancer presenting as cancer of unknown primary origin, it is important to determine the tumor origin. Prostate-specific antigen is used as a diagnostic marker for prostate cancer but the expression declines with progression to castration-resistant prostate cancer. Aim of this study was to identify the most informative marker constellation, which is able to detect metastatic prostate cancer at high sensitivity. The widely used prostate cancer markers such as prostate-specific antigen, prostate-specific acid phosphatase, androgen receptor, prostate-specific membrane antigen, prostein, and ETS-related gene were investigated for their sensitivity to detect prostatic origin of metastases. Expression of prostate-specific antigen, prostate-specific acid phosphatase, androgen receptor, prostate-specific membrane antigen, prostein, and ETS-related gene was determined on archived tissue specimens consisting of benign prostatic tissue (n ¼ 9), primary prostate cancer (n ¼ 79), lymph node metastases (n ¼ 58), and distant metastases (n ¼ 39) using immunohistochemistry. The staining intensity was categorized as negative (0), weak (1), moderate (2), and strong (3). All markers except ETS-related gene were able to detect at least 70% of lymph node metastases and distant metastases, with prostate-specific antigen, androgen receptor, and prostate-specific membrane antigen having the highest sensitivity (97%, 91%, and 94%, respectively). A further increase of the sensitivity up to 98% and 100% could be achieved by the combination of prostate-specific antigen, prostate-specific membrane antigen, or androgen receptor for lymph node metastases and for distant metastases, respectively. The same sensitivity could be reached by combining prostate-specific membrane antigen and prostein. Our data show that a combined staining of at least two prostate markers should be utilized to identify metastases as originating from prostate cancer. Modern Pathology (2015) 28, 138-145; doi:10.1038/modpathol.2014 published online 13 June 2014 Prostate cancer is the most commonly diagnosed non-epidermal cancer and second-most common cancer-related cause of death in men in the western world. 1 The patients' death is often caused by the development of castration-resistant prostate cancer. Most prostate cancers are detected early in a localized stage; however, in some cases, metastases can be the first manifestation of a prostate cancer. 2 Unlike other carcinomas, hormone-sensitive prostate cancer responds to hormonal therapy and therefore the identification of the tumor origin is important in order to allow specific treatment. Male patients with a metastatic adenocarcinoma are routinely assessed for prostatic origin using prostate-specific immunohistochemistry markers like prostate-specific antigen (PSA). 3 PSA is highly expressed in benign prosta...

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Section: Discussionmentioning

confidence: 99%

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Queisser¹,

Hagedorn²,

Braun³

et al. 2015

Modern Pathology

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“…Overexpression of GRPR was found in 63%-100% of primary prostate tumors and more than 50% of lymph and bone metastases (8,9). The GRPR density was reported to be 26-fold higher in prostate carcinoma than prostatic hyperplasia (9).…”

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confidence: 99%

Preclinical Comparison of Al¹⁸F- and ⁶⁸Ga-Labeled Gastrin-Releasing Peptide Receptor Antagonists for PET Imaging of Prostate Cancer

et al. 2014

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International audienceGastrin-releasing peptide receptor (GRPR) is overexpressed in human prostate cancer and is being used as a target for molecular imaging. In this study, we report on the direct comparison of 3 novel GRPR-targeted radiolabeled tracers: Al18F-JMV5132, 68Ga-JMV5132, and 68Ga-JMV4168 (JMV5132 is NODA-MPAA-βAla-βAla-[H-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2], JMV4168 is DOTA-βAla-βAla-[H-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2], and NODA-MPAA is 2-[4-(carboxymethyl)-7-{[4-(carboxymethyl)phenyl]methyl}-1,4,7-triazacyclononan-1-yl]acetic acid). Methods: The GRPR antagonist JMV594 (H-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) was conjugated to NODA-MPAA for labeling with Al18F. JMV5132 was radiolabeled with 68Ga and 18F, and JMV4168 was labeled with 68Ga for comparison. The inhibitory concentration of 50% values for binding GRPR of JMV4168, JMV5132, natGa-JMV4168, and natGa-JMV5132 were determined in a competition-binding assay using GRPR-overexpressing PC-3 tumors. The tumor-targeting characteristics of the compounds were assessed in mice bearing subcutaneous PC-3 xenografts. Small-animal PET/CT images were acquired, and tracer biodistribution was determined by ex vivo measurements. Results: JMV5132 was labeled with 18F in a novel 1-pot, 1-step procedure within 20 min, without need for further purification and resulting in a specific activity of 35 MBq/nmol. Inhibitory concentration of 50% values (in nM) for GRPR binding of JMV5132, JMV4168, natGa-JMV5132, natGa-JMV4168, and AlnatF-JMV5132 were 6.8 (95% confidence intervals [CIs], 4.6–10.0), 13.2 (95% CIs, 5.9–29.3), 3.0 (95% CIs, 1.5–6.0), 3.2 (95% CIs, 1.8–5.9), and 10.0 (95% CIs, 6.3–16.0), respectively. In mice with subcutaneous PC-3 xenografts, all tracers cleared rapidly from the blood, exclusively via the kidneys for 68Ga-JMV4168 and partially hepatobiliary for 68Ga-JMV5132 and Al18F-JMV5132. Two hours after injection, the uptake of 68Ga-JMV4168, 68Ga-JMV5132, and Al18F-JMV5132 in PC-3 tumors was 5.96 ± 1.39, 5.24 ± 0.29, 5.30 ± 0.98 (percentage injected dose per gram), respectively. GRPR specificity was confirmed by significantly reduced tumor uptake of the 3 tracers after coinjection of a 100-fold excess of unlabeled JMV4168 or JMV5132. Small-animal PET/CT clearly visualized PC-3 tumors, with the highest resolution observed for Al18F-JMV5132. Conclusion: JMV5132 could be rapidly and efficiently labeled with 18F. Al18F-JMV5132, 68Ga-JMV5132, and 68Ga-JMV4168 all showed comparable high and specific accumulation in GRPR-positive PC-3 tumors. These new PET tracers are promising candidates for future clinical translation

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“…Virtually all prostate cancer primary tumors express PSMA (Wright, Haley et al 1995;Murphy, Elgamal et al 1998;Kusumi, Koie et al 2008;Ananias, van den Heuvel et al 2009;Mannweiler, Amersdorfer et al 2009), whereas PSMA expressed in prostate vascular endothelium of benign tissue (Chang, O'Keefe et al 1999). PSMA levels increase progressively in higher-grade cancers, metastatic disease, hormone-refractory cancer, progressing cancer, and cancers exhibiting rising blood PSA following prostatectomy (Israeli, Miller et al 1994;Wright, Haley et al 1995;Wright, Mayer Grob et al 1996;Sweat, Pacelli et al 1998;Ross, Sheehan et al 2003;Perner, Hofer et al 2007;Minner, Wittmer et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Immunocapture of prostate cancer cells with anti-PSMA antibodies in microdevices

Santana

Liu

Bander

et al. 2011

2011 IEEE 37th Annual Northeast Bioengineering Conference (NEBEC)

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Patients suffering from cancer can shed tumor cells into the bloodstream, leading to one of the most important mechanisms of metastasis. As such, the capture of these cells is of great interest. Circulating tumor cells are typically extracted from circulation through positive selection with the epithelial cell-adhesion molecule (EpCAM), leading to currently unknown biases when cells are undergoing epithelial-to-mesenchymal transition. For prostate cancer, prostate-specific membrane antigen (PSMA) presents a compelling target for immunocapture, as PSMA levels increase in higher-grade cancers and metastatic disease and are specific to the prostate epithelium. This study uses monoclonal antibodies J591 and J415-antibodies that are highly specific for intact extracellular domains of PSMA on live cells-in microfluidic devices for the capture of LNCaPs, a PSMA-expressing immortalized prostate cancer cell line, over a range of concentrations and shear stresses relevant to immunocapture. Our results show that J591 outperforms J415 and a mix of the two for prostate cancer capture, and that capture performance saturates following incubation with antibody concentrations of 10 micrograms per milliliter.

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Expression of the gastrin‐releasing peptide receptor, the prostate stem cell antigen and the prostate‐specific membrane antigen in lymph node and bone metastases of prostate cancer

Cited by 143 publications

References 49 publications

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Preclinical Comparison of Al¹⁸F- and ⁶⁸Ga-Labeled Gastrin-Releasing Peptide Receptor Antagonists for PET Imaging of Prostate Cancer

Immunocapture of prostate cancer cells with anti-PSMA antibodies in microdevices

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Expression of the gastrin‐releasing peptide receptor, the prostate stem cell antigen and the prostate‐specific membrane antigen in lymph node and bone metastases of prostate cancer

Cited by 143 publications

References 49 publications

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Preclinical Comparison of Al18F- and 68Ga-Labeled Gastrin-Releasing Peptide Receptor Antagonists for PET Imaging of Prostate Cancer

Immunocapture of prostate cancer cells with anti-PSMA antibodies in microdevices

Contact Info

Product

Resources

About

Preclinical Comparison of Al¹⁸F- and ⁶⁸Ga-Labeled Gastrin-Releasing Peptide Receptor Antagonists for PET Imaging of Prostate Cancer