Prospects of targeting the gastrin releasing peptide receptor and somatostatin receptor 2 for nuclear imaging and therapy in metastatic breast cancer

Simone U. Dalm, Willemijne A.M.E. Schrijver, Anieta M. Sieuwerts, Maxime P. Look, Angelique C.J. Ziel-Van Der Made, Vanja De Weerd, John W. Martens, Paul J. Van Diest, Marion De Jong, Carolien H.M. Van Deurzen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere0170536
JournalPloS one
Volume12
Issue number1
DOIs
StatePublished - Jan 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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