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

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 usin...

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Veröffentlicht in:PloS one Jg. 14; H. 1; S. e0210905
Hauptverfasser: Morgat, Clément, Schollhammer, Romain, Macgrogan, Gaétan, Barthe, Nicole, Vélasco, Valérie, Vimont, Delphine, Cazeau, Anne-Laure, Fernandez, Philippe, Hindié, Elif
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 2019
Public Library of Science (PLoS)
Schlagworte:
Binding
Binding sites
Biology and Life Sciences
Breast cancer
Breast Neoplasms - diagnostic imaging
Breast Neoplasms - metabolism
Cancer
Cancer therapies
Chemotherapy
Computed tomography
ErbB-2 protein
Estrogen receptors
Estrogens
Female
Fluorine isotopes
Fluorodeoxyglucose F18 - pharmacokinetics
Gallium Radioisotopes - pharmacokinetics
Gastrin
Gastrin-releasing peptide
Hospitals
Humans
Immunohistochemistry
Lutetium
Lymph nodes
Lymphatic Metastasis - diagnostic imaging
Lymphatic system
Medical diagnosis
Medical imaging
Medical treatment
Medicine and Health Sciences
Metastases
Metastasis
Nodes
Nuclear medicine
Oligopeptides - pharmacokinetics
Overexpression
Patients
Peptides
Positron emission tomography
Positron Emission Tomography Computed Tomography
Progesterone
Prostate cancer
Radiation therapy
Radioisotopes
Radiopharmaceuticals - pharmacokinetics
Receptor, ErbB-2 - metabolism
Receptors, Bombesin - antagonists & inhibitors
Receptors, Bombesin - metabolism
Receptors, Estrogen - metabolism
Receptors, Progesterone - metabolism
Research and Analysis Methods
Retrospective Studies
Studies
Surgery
Tumors
France
ISSN:1932-6203, 1932-6203
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Zusammenfassung: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.
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Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0210905