Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples

PLoS One. 2019 Jan 15;14(1):e0210905. doi: 10.1371/journal.pone.0210905. eCollection 2019.


The Gastrin-Releasing Peptide Receptor (GRPR) is over-expressed in estrogen receptor (ER) positive breast tumors and related metastatic lymph nodes offering the opportunity of imaging and therapy of luminal tumors. 68Ga-RM2 binding and 18F-FDG binding in tumoral zones were measured and compared using tissue micro-imaging with a beta imager on 14 breast cancer samples (10 primaries and 4 associated metastatic lymph nodes). Results were then assessed against ER expression, progesterone receptor (PR) expression, HER2 over-expression or not and Ki-67 expression. GRPR immunohistochemistry (IHC) was also performed on all samples. We also retrospectively compared 68Ga-RM2 and 18F-FDG bindings to 18F-FDG SUVmax on the pre-therapeutic PET/CT examination, if available. 68Ga-RM2 binding was significantly higher in tumors expressing GRPR on IHC than in GRPR-negative tumors (P = 0.022). In ER+ tumors, binding of 68Ga-RM2 was significantly higher than 18F-FDG (P = 0.015). In tumors with low Ki-67, 68Ga-RM2 binding was also significantly increased compared to 18F-FDG (P = 0.029). Overall, the binding of 68Ga-RM2 and 18F-FDG displayed an opposite pattern in tumor samples and 68Ga-RM2 binding was significantly higher in tumors that had low 18F-FDG binding (P = 0.021). This inverse correlation was also documented in the few patients in whom a 18F-FDG PET/CT examination before surgery was available. Findings from this in vitro study suggest that GRPR targeting can be an alternative to 18F-FDG imaging in ER+ breast tumors. Moreover, because GRPR antagonists can also be labeled with lutetium-177 this opens new avenues for targeted radionuclide therapy in the subset of patients with progressive metastatic disease following conventional treatments.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / metabolism*
  • Female
  • Fluorodeoxyglucose F18 / pharmacokinetics*
  • Gallium Radioisotopes / pharmacokinetics
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis / diagnostic imaging
  • Oligopeptides / pharmacokinetics*
  • Positron Emission Tomography Computed Tomography
  • Radiopharmaceuticals / pharmacokinetics
  • Receptor, ErbB-2 / metabolism
  • Receptors, Bombesin / antagonists & inhibitors
  • Receptors, Bombesin / metabolism*
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Retrospective Studies


  • BAY 86-7548
  • Gallium Radioisotopes
  • Oligopeptides
  • Radiopharmaceuticals
  • Receptors, Bombesin
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Fluorodeoxyglucose F18
  • ERBB2 protein, human
  • Receptor, ErbB-2

Grant support

This study was funded by "La ligue contre le Cancer Gironde".