Theranostics 2016; 6(10):1641-1650. doi:10.7150/thno.14958
Gastrin-releasing Peptide Receptor Imaging in Breast Cancer Using the Receptor Antagonist 68Ga-RM2 And PET
1. Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany;
2. Department of Obstetrics and Gynecology, University Medical Center Freiburg, Germany;
3. Department of Clinical Pathology, University Medical Center Freiburg, Germany;
4. German Cancer Research Center (DKFZ), Heidelberg, Germany;
5. German Cancer Consortium (DKTK), Freiburg, Germany;
6. Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, United States of America;
7. Department of Gynecology and Obstetrics, University Hospital Aachen, Germany;
8. Tumorbank, Comprehensive Cancer Center Freiburg, University Medical Center Freiburg, Germany.
*Both authors contributed equally.
Stoykow C, Erbes T, Maecke HR, Bulla S, Bartholomä M, Mayer S, Drendel V, Bronsert P, Werner M, Gitsch G, Weber WA, Stickeler E, Meyer PT. Gastrin-releasing Peptide Receptor Imaging in Breast Cancer Using the Receptor Antagonist 68Ga-RM2 And PET. Theranostics 2016; 6(10):1641-1650. doi:10.7150/thno.14958. Available from https://www.thno.org/v06p1641.htm
Introduction: 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 68Ga-RM2.
Methods: Fifteen female patients with biopsy confirmed primary breast carcinoma (3 bilateral tumors; median clinical stage IIB) underwent 68Ga-RM2-PET/CT for pretreatment staging. In vivo tumor uptake of 68Ga-RM2 was correlated with estrogen (ER) and progesterone (PR) receptor expression, HER2/neu status and MIB-1 proliferation index in breast core biopsy specimens.
Results: 13/18 tumors demonstrated strongly increased 68Ga-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 68Ga-RM2 uptake (model: r2=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, 68Ga-RM2-PET/CT detected internal mammary lymph nodes with high 68Ga-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).
Conclusion: Our study demonstrates that 68Ga-RM2-PET/CT is a promising imaging method in ER-positive breast cancer. In vivo GRPR binding assessed by 68Ga-RM2-PET/CT correlated with ER expression in primary tumors of untreated patients.
Keywords: GRPR, gastrin-releasing peptide receptor, bombesin, PET, positron emission tomography, breast cancer, ER, estrogen receptor.