Open AccessComparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples
Author(s) -
Clément Morgat,
Romain Schollhammer,
Gaëtan MacGrogan,
Nicole Barthe,
Valérie Velasco,
Delphine Vimont,
AnneLaure Cazeau,
Philippe Fernandez,
Elif Hindié
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0210905
Subject(s) - immunohistochemistry , medicine , breast cancer , cancer research , estrogen receptor , lymph , receptor , progesterone receptor , cancer , pathology , oncology
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. 68 Ga-RM2 binding and 18 F-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 68 Ga-RM2 and 18 F-FDG bindings to 18 F-FDG SUV max on the pre-therapeutic PET/CT examination, if available. 68 Ga-RM2 binding was significantly higher in tumors expressing GRPR on IHC than in GRPR-negative tumors ( P = 0.022). In ER + tumors, binding of 68 Ga-RM2 was significantly higher than 18 F-FDG ( P = 0.015). In tumors with low Ki-67, 68 Ga-RM2 binding was also significantly increased compared to 18 F-FDG ( P = 0.029). Overall, the binding of 68 Ga-RM2 and 18 F-FDG displayed an opposite pattern in tumor samples and 68 Ga-RM2 binding was significantly higher in tumors that had low 18 F-FDG binding ( P = 0.021). This inverse correlation was also documented in the few patients in whom a 18 F-FDG PET/CT examination before surgery was available. Findings from this in vitro study suggest that GRPR targeting can be an alternative to 18 F-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.