Gastrin-Releasing Peptide Receptor Antagonist [(68)Ga]RM2 PET/CT for Staging of Pre-Treated, Metastasized Breast Cancer

SIMPLE SUMMARY: [(68)Ga]RM2 positron emission tomography (PET)/computed tomography (CT) has shown to be a promising imaging method for primary breast cancer (BC) with positive estrogen receptor (ER) status, but it has not been tested for visualization of metastasized recurrent or progressive BC. The aim of this pilot study was to assess tumor visualization using [(68)Ga]RM2 PET/CT in patients with pre-treated ER-positive BC and suspected metastases. Eight female patients with initial ER-positive, pre-treated BC were included in this retrospective study. Strong RM2 binding was found in all metastatic lesions of six patients, whereas two patients were rated RM2-negative. Our data suggest that RM2 binding is maintained in the majority of patients with advanced disease stage of pre-treated ER-positive BC. Thus, [(68)Ga]RM2 PET/CT could support treatment decision in these patients, radiotherapy planning in oligometastatic patients or selection of patients for RM2 radioligand therapy. ABSTRACT: Background: Positron emission tomography (PET)/computed tomography (CT) using the gastrin-releasing peptide receptor antagonist [(68)Ga]RM2 has shown to be a promising imaging method for primary breast cancer (BC) with positive estrogen receptor (ER) status. This study assessed tumor visualization by [(68)Ga]RM2 PET/CT in patients with pre-treated ER-positive BC and suspected metastases. Methods: This retrospective pilot study included eight female patients with initial ER-positive, pre-treated BC who underwent [(68)Ga]RM2 PET/CT. Most of these patients (seven out of eight; 88%) were still being treated with or had received endocrine therapy. [(68)Ga]RM2 PET/CTs were visually analyzed by two nuclear medicine specialists in consensus. Tumor manifestations were rated qualitatively (i.e., RM2-positive or RM2-negative) and quantitatively using the maximum standardized uptake value (SUVmax). SUVmax values were compared between the two subgroups (RM2-positive vs. RM2-negative). Results: Strong RM2 binding was found in all metastatic lesions of six patients (75%), whereas tracer uptake in all metastases of two patients (25%) was rated negative. Mean SUVmax of RM2-positive metastases with the highest SUVmax per patient (in lymph node and bone metastases; 15.8 ± 15.1 range: 3.7–47.8) was higher than mean SUVmax of the RM2-negative metastases with the highest SUVmax per patient (in bone metastases; 1.6 ± 0.1, range 1.5–1.7). Conclusions: Our data suggest that RM2 binding is maintained in the majority of patients with advanced disease stage of pre-treated ER-positive BC. Thus, [(68)Ga]RM2 PET/CT could support treatment decision in these patients, radiotherapy planning in oligometastatic patients or selection of patients for RM2 radioligand therapy. Further studies with larger patient cohorts are warranted to confirm these findings.