RT Journal Article
SR Electronic
T1 In Vitro and In Vivo Application of Radiolabeled Gastrin-Releasing Peptide Receptor Ligands in Breast Cancer
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 752
OP 757
DO 10.2967/jnumed.114.153023
VO 56
IS 5
A1 Dalm, Simone U.
A1 Martens, John W.M.
A1 Sieuwerts, Anieta M.
A1 van Deurzen, Carolien H.M.
A1 Koelewijn, Stuart J.
A1 de Blois, Erik
A1 Maina, Theodosia
A1 Nock, Berthold A.
A1 Brunel, Luc
A1 Fehrentz, Jean-Alain
A1 Martinez, Jean
A1 de Jong, Marion
A1 Melis, Marleen
YR 2015
UL http://jnm.snmjournals.org/content/56/5/752.abstract
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.