title: Gastrin-releasing Peptide Receptor Imaging in Breast Cancer Using the Receptor Antagonist (68)Ga-RM2 And PET.
abstract: The gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer. The present study evaluates GRPR imaging as a novel imaging modality in breast cancer by employing positron emission tomography (PET) and the GRPR antagonist (68)Ga-RM2.
  
  
  
  Fifteen female patients with biopsy confirmed primary breast carcinoma (3 bilateral tumors; median clinical stage IIB) underwent (68)Ga-RM2-PET/CT for pretreatment staging. In vivo tumor uptake of (68)Ga-RM2 was correlated with estrogen (ER) and progesterone (PR) receptor expression, HER2/neu status and MIB-1 proliferation index in breast core biopsy specimens.
  
  
  
  13/18 tumors demonstrated strongly increased (68)Ga-RM2 uptake compared to normal breast tissue (defined as PET-positive). All PET-positive primary tumors were ER- and PR-positive (13/13) in contrast to only 1/5 PET-negative tumors. Mean SUVMAX of ER-positive tumors was 10.6±6.0 compared to 2.3±1.0 in ER-negative tumors (p=0.016). In a multivariate analysis including ER, PR, HER2/neu and MIB-1, only ER expression predicted (68)Ga-RM2 uptake (model: r(2) =0.55, p=0.025). Normal breast tissue showed inter- and intraindividually variable, moderate GRPR binding (SUVMAX 2.3±1.0), while physiological uptake of other organs was considerably less except pancreas. Of note, (68)Ga-RM2-PET/CT detected internal mammary lymph nodes with high (68)Ga-RM2 uptake (n=8), a contralateral axillary lymph node metastasis (verified by biopsy) and bone metastases (n=1; not detected by bone scan and CT).
  
  
  
  Our study demonstrates that (68)Ga-RM2-PET/CT is a promising imaging method in ER-positive breast cancer. In vivo GRPR binding assessed by (68)Ga-RM2-PET/CT correlated with ER expression in primary tumors of untreated patients.
authors.affiliation: 1. Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany;; 4. German Cancer Research Center (DKFZ), Heidelberg, Germany;; 5. German Cancer Consortium (DKTK), Freiburg, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Stoykow
authors.affiliation: 2. Department of Obstetrics and Gynecology, University Medical Center Freiburg, Germany;
authors.forename: Thalia
authors.initials: T
authors.lastname: Erbes
authors.affiliation: 1. Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany;; 5. German Cancer Consortium (DKTK), Freiburg, Germany;
authors.forename: Helmut R
authors.initials: HR
authors.lastname: Maecke
authors.affiliation: 1. Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany;
authors.forename: Stefan
authors.initials: S
authors.lastname: Bulla
authors.affiliation: 1. Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany;
authors.forename: Mark
authors.initials: M
authors.lastname: Bartholomä
authors.affiliation: 2. Department of Obstetrics and Gynecology, University Medical Center Freiburg, Germany;
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mayer
authors.affiliation: 3. Department of Clinical Pathology, University Medical Center Freiburg, Germany;
authors.forename: Vanessa
authors.initials: V
authors.lastname: Drendel
authors.affiliation: 3. Department of Clinical Pathology, University Medical Center Freiburg, Germany;; 5. German Cancer Consortium (DKTK), Freiburg, Germany;; 8. Tumorbank, Comprehensive Cancer Center Freiburg, University Medical Center Freiburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bronsert
authors.affiliation: 3. Department of Clinical Pathology, University Medical Center Freiburg, Germany;; 5. German Cancer Consortium (DKTK), Freiburg, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.affiliation: 2. Department of Obstetrics and Gynecology, University Medical Center Freiburg, Germany;
authors.forename: Gerald
authors.initials: G
authors.lastname: Gitsch
authors.affiliation: 6. Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, United States of America;
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Weber
authors.affiliation: 7. Department of Gynecology and Obstetrics, University Hospital Aachen, Germany;
authors.forename: Elmar
authors.initials: E
authors.lastname: Stickeler
authors.affiliation: 1. Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany;; 5. German Cancer Consortium (DKTK), Freiburg, Germany;
authors.forename: Philipp T
authors.initials: PT
authors.lastname: Meyer
mesh_terms: D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D018004:Receptors, Bombesin / Q000032:analysis* / Q000037:antagonists & inhibitors
chemical_list: C582579:BAY 86-7548; D009842:Oligopeptides; D018004:Receptors, Bombesin
keywords: ER; GRPR; PET; bombesin; breast cancer; estrogen receptor.; gastrin-releasing peptide receptor; positron emission tomography