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. 2017 Jan 20;12(1):e0170536.
doi: 10.1371/journal.pone.0170536. eCollection 2017.

Prospects of Targeting the Gastrin Releasing Peptide Receptor and Somatostatin Receptor 2 for Nuclear Imaging and Therapy in Metastatic Breast Cancer

Simone U Dalm  1 , Willemijne A M E Schrijver  2 , Anieta M Sieuwerts  3 , Maxime P Look  3 , Angelique C J Ziel-van der Made  4 , Vanja de Weerd  3 , John W Martens  3 , Paul J van Diest  2 , Marion de Jong  1 , Carolien H M van Deurzen  4
Affiliations

Prospects of Targeting the Gastrin Releasing Peptide Receptor and Somatostatin Receptor 2 for Nuclear Imaging and Therapy in Metastatic Breast Cancer

Simone U Dalm et al. PLoS One. .

Abstract

Background: The gastrin releasing peptide receptor (GRPR) and the somatostatin receptor 2 (SSTR2) are overexpressed on primary breast cancer (BC), making them ideal candidates for receptor-mediated nuclear imaging and therapy. The aim of this study was to determine whether these receptors are also suitable targets for metastatic BC.

Methods: mRNA expression of human BC samples were studied by in vitro autoradiography and associated with radioligand binding. Next, GRPR and SSTR2 mRNA levels of 60 paired primary BCs and metastases from different sites were measured by quantitative reverse transcriptase polymerase chain reaction. Receptor mRNA expression levels were associated with clinico-pathological factors and expression levels of primary tumors and corresponding metastases were compared.

Results: Binding of GRPR and SSTR radioligands to tumor tissue correlated significantly with receptor mRNA expression. High GRPR and SSTR2 mRNA levels were associated with estrogen receptor (ESR1)-positive tumors (p<0.001 for both receptors). There was no significant difference in GRPR mRNA expression of primary tumors versus paired metastases. Regarding SSTR2 mRNA expression, there was also no significant difference in the majority of cases, apart from liver and ovarian metastases which showed a significantly lower expression compared to the corresponding primary tumors (p = 0.02 and p = 0.03, respectively).

Conclusion: Targeting the GRPR and SSTR2 for nuclear imaging and/or treatment has the potential to improve BC care in primary as well as metastatic disease.

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Conflict of interest statement

MdJ is shareholder of Advanced Accelerator Applications. We don't have any other potential conflicts of interest to report. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. In vitro autoradiography of primary BC and corresponding regional lymph node metastases.
A. Hematoxylin and eosin (H&E) staining and autoradiography results after incubating cells with the GRPR radioligand, 111In-JMV4168, and the SSTR2 radioligand, 111In-DOTA-Tyr3-octreotate. B+D. Correlation of quantified autoradiography results (% AD) with mRNA expression of fresh frozen (FF) tissue. C+E. Correlation of mRNA expression of FF and formalin fixed paraffin embedded (FFPE) tissue of the same tumor.
Fig 2
Fig 2. GRPR and SSTR2 mRNA levels in primary BC (PBC) and corresponding metastases (BCM).
Significant differences are indicated by *.
See this image and copyright information in PMC

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