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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Main Authors: Clément Morgat, Romain Schollhammer, Gaétan Macgrogan, Nicole Barthe, Valérie Vélasco, Delphine Vimont, Anne-Laure Cazeau, Philippe Fernandez, Elif Hindié
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0210905
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author Clément Morgat
Romain Schollhammer
Gaétan Macgrogan
Nicole Barthe
Valérie Vélasco
Delphine Vimont
Anne-Laure Cazeau
Philippe Fernandez
Elif Hindié
author_facet Clément Morgat
Romain Schollhammer
Gaétan Macgrogan
Nicole Barthe
Valérie Vélasco
Delphine Vimont
Anne-Laure Cazeau
Philippe Fernandez
Elif Hindié
author_sort Clément Morgat
collection DOAJ
description 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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spelling doaj.art-677846a9de1342ae8fb76680bad8197f2022-12-21T19:50:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01141e021090510.1371/journal.pone.0210905Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples.Clément MorgatRomain SchollhammerGaétan MacgroganNicole BartheValérie VélascoDelphine VimontAnne-Laure CazeauPhilippe FernandezElif HindiéThe 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.https://doi.org/10.1371/journal.pone.0210905
spellingShingle Clément Morgat
Romain Schollhammer
Gaétan Macgrogan
Nicole Barthe
Valérie Vélasco
Delphine Vimont
Anne-Laure Cazeau
Philippe Fernandez
Elif Hindié
Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples.
PLoS ONE
title Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples.
title_full Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples.
title_fullStr Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples.
title_full_unstemmed Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples.
title_short Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples.
title_sort comparison of the binding of the gastrin releasing peptide receptor grp r antagonist 68ga rm2 and 18f fdg in breast cancer samples
url https://doi.org/10.1371/journal.pone.0210905
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