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Theranostics 2016; 6(10):1641-1650. doi:10.7150/thno.14958 This issue Cite

Research Paper

Gastrin-releasing Peptide Receptor Imaging in Breast Cancer Using the Receptor Antagonist ⁶⁸Ga-RM2 And PET

Christian Stoykow^1,4,5✉*, Thalia Erbes^2*, Helmut R Maecke^1,5, Stefan Bulla¹, Mark Bartholomä¹, Sebastian Mayer², Vanessa Drendel³, Peter Bronsert^3,5,8, Martin Werner^3,5, Gerald Gitsch², Wolfgang A Weber⁶, Elmar Stickeler⁷, Philipp T Meyer^1,5

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.

✉ Corresponding author: Christian Stoykow, Department of Nuclear Medicine, University Medical Center Freiburg, Hugstetter Str. 55, 79106, Freiburg, Tel.: +49-761-27074210; Fax: +49-761-27073500; eMail: christian.stoykowde.

Abstract

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 SUV_MAX 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 (SUV_MAX 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.

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