PT  - JOURNAL ARTICLE
AU  - Simone U. Dalm
AU  - John W.M. Martens
AU  - Anieta M. Sieuwerts
AU  - Carolien H.M. van Deurzen
AU  - Stuart J. Koelewijn
AU  - Erik de Blois
AU  - Theodosia Maina
AU  - Berthold A. Nock
AU  - Luc Brunel
AU  - Jean-Alain Fehrentz
AU  - Jean Martinez
AU  - Marion de Jong
AU  - Marleen Melis
TI  - In Vitro and In Vivo Application of Radiolabeled Gastrin-Releasing Peptide Receptor Ligands in Breast Cancer
AID  - 10.2967/jnumed.114.153023
DP  - 2015 May 01
TA  - Journal of Nuclear Medicine
PG  - 752--757
VI  - 56
IP  - 5
4099  - http://jnm.snmjournals.org/content/56/5/752.short
4100  - http://jnm.snmjournals.org/content/56/5/752.full
SO  - J Nucl Med2015 May 01; 56
AB  - Breast cancer (BC) consists of multiple subtypes defined by various molecular characteristics, for instance, estrogen receptor (ER) expression. Methods for visualizing BC include mammography, MR imaging, ultrasound, and nuclear medicine–based methods such as 99mTc-sestamibi and 18F-FDG PET, unfortunately all lacking specificity. Peptide receptor scintigraphy and peptide receptor radionuclide therapy are successfully applied for imaging and therapy of somatostatin receptor–expressing neuroendocrine tumors using somatostatin receptor radioligands. On the basis of a similar rationale, radioligands targeting the gastrin-releasing peptide receptor (GRP-R) might offer a specific method for imaging and therapy of BC. The aim of this study was to explore the application of GRP-R radioligands for imaging and therapy of BC by introducing valid preclinical in vitro and in vivo models. Methods: GRP-R expression of 50 clinical BC specimens and the correlation with ER expression was studied by in vitro autoradiography with the GRP-R agonist 111In-AMBA. GRP-R expression was also analyzed in 9 BC cell lines applying 111In-AMBA internalization assays and quantitative reverse transcriptase polymerase chain reaction. In vitro cytotoxicity of 177Lu-AMBA was determined on the GRP-R–expressing BC cell line T47D. SPECT/CT imaging and biodistribution were studied in mice with subcutaneous and orthotopic ER-positive T47D and MCF7 xenografts after injection of the GRP-R antagonist 111In-JMV4168. Results: Most of the human BC specimens (96%) and BC cell lines (6/9) were found to express GRP-R. GRP-R tumor expression was positively (P = 0.026, χ2(4) = 12,911) correlated with ER expression in the human BC specimens. Treatment of T47D cells with 10−7 M/50 MBq of 177Lu-AMBA resulted in 80% reduction of cells in vitro. Furthermore, subcutaneous and orthotopic tumors from both BC cell lines were successfully visualized in vivo by SPECT/CT using 111In-JMV4168; T47D tumors exhibited a higher uptake than MCF7 xenografts. Conclusion: Targeting GRP-R–expressing BC tumors using GRP-R radioligands is promising for nuclear imaging and therapy, especially in ER-positive BC patients.