Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples
PLoS ONE. 2019-01-15; 14(1): e0210905
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1. PLoS One. 2019 Jan 15;14(1):e0210905. doi: 10.1371/journal.pone.0210905.
Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R)
antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples.
Morgat C(1)(2)(3), Schollhammer R(1)(2)(3), Macgrogan G(4)(5), Barthe N(6),
Vélasco V(4)(5), Vimont D(2)(3), Cazeau AL(7), Fernandez P(1)(2)(3), Hindié
(1)Nuclear Medicine Department, University Hospital of Bordeaux, Bordeaux,
(2)Univ. Bordeaux, INCIA, UMR-CNRS 5287, Talence, France.
(3)CNRS, INCIA, UMR 5287, Talence, France.
(4)Surgical Pathology Unit, Department of BioPathology, Institut Bergonié,
(5)INSERM, ACTION U1218, Bordeaux, France.
(6)BioTis, INSERM U1026, Bordeaux, France.
(7)Nuclear Medicine Department, Institut Bergonié, Bordeaux, France.
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.
PMID: 30645633 [Indexed for MEDLINE]
Conflict of interest statement: The authors have declared that no competing