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

Abstract

Background: Positron emission tomography (PET)/computed tomography (CT) using the gastrin-releasing peptide receptor antagonist [68Ga]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 [68Ga]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 [68Ga]RM2 PET/CT. Most of these patients (seven out of eight; 88%) were still being treated with or had received endocrine therapy. [68Ga]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, [68Ga]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.

Structures of human gastrin-releasing peptide receptors bound to antagonist and agonist for cancer and itch therapy

“…GRPR is one of the most commonly overexpressed receptors in prostate ( 5 , 6 ), breast ( 7 ) and lung cancer ( 8 ). And GRPR mediates the transmission of non-histaminergic itch in the dorsal horn of the spinal cord ( 25 ).…”

“…These receptors are widely distributed in the central nerve system (CNS) and peripheral tissues with extensive effects on the physiological and pathological processes ( 4 ). Mammalian BBN receptors, especially GRPR, are of particular interest in oncology as their high expression in several human cancers, such as the prostate ( 5 , 6 ), breast ( 7 ), and small-cell lung cancers ( 8 ), as well as in the CNS/neural tumors including gliomas, neuroblastomas, and medulloblastomas ( 9 ). BBN is a 14-residue peptide (Pyr-QRLGNQWAVGHLM-NH 2 ) first isolated from the skin of the European fire-bellied toad Bombina bombina and its mammalian counterpart gastrin-releasing peptide (GRP), a 27-residue peptide, shares the same C terminus of Trp-Ala-Val-Gly-His-Leu-Met-NH 2 with BBN ( 10 ).…”

64Cu-SAR-Bombesin PET-CT Imaging in the Staging of Estrogen/Progesterone Receptor Positive, HER2 Negative Metastatic Breast Cancer Patients: Safety, Dosimetry and Feasibility in a Phase I Trial

“…Of note, Michalski et al reported two of two ER-positive metastatic ILC patients negative on GRPR PET. [ 24 ] Both patients reported current endocrine therapy for a duration of at least 18 months and one of two patients subsequently had loss of ER expression on examination of metastatic breast cancer cells. In our study, neither patient with ILC was on endocrine therapy at the time of imaging.…”

Non-conventional and Investigational PET Radiotracers for Breast Cancer: A Systematic Review

“…In 2021, a new study from the same group ( 215 ) on eight female patients with initial ER+ BC, demonstrated how [ 68 Ga]Ga-RM2 PET/CT could support treatment decisions in these patients, guide radiotherapy planning in oligometastatic patients or select patients for RM2 radioligand therapy.…”