Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist (68)Ga-RM2 and (18)F-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. (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.