Abstract
INTRODUCTION: Recent studies showed enhanced tumor targeting by novel somatostatin receptor (SSTR) antagonists compared to clinically widely used agonists. However, these results have mostly been obtained in neuroendocrine tumors and only limited data is available for cancer types with lower SSTR expression, including breast cancer (BC). To date, only two studies reported higher binding of the antagonist versus the agonist in BC, but in both studies a limited number of cases were evaluated. In this pre-clinical study, we further investigated whether the application of a SSTR antagonist could improve SSTR-mediated BC imaging in a large panel of BC specimens. We also generated an in vivo BC mouse model and performed single-photon emission computed tomography/Magnetic resonance imaging (SPECT/MRI) and biodistribution studies. MATERIALS AND METHODS: 111In-DOTA-Tyr3-octreotate (SSTR agonist) and 111In-DOTA-JR11 (SSTR antagonist) binding to 40 human BC specimens was compared using in vitro autoradiography. SSTR2-immunostaining was performed to confirm SSTR2 expression of the tumor cells. Furthermore, binding of the radiolabeled SSTR agonist and antagonist was analyzed in tissue material from 6 patient derived xenografts (pdx’s). One pdx, the estrogen receptor positive model T126, was chosen to generate in vivo mouse models containing orthotopic breast tumors for in vivo SPECT/MR imaging and biodistribution studies after injection with 177Lu-DOTA-Tyr3-octreotate or 177Lu-DOTA-JR11. RESULTS: 111In-DOTA-JR11 binding to human BC tissue was significantly higher than 111In-DOTA-Tyr3-octreotate binding (p<0.001). The median (interquartile range) ratio of the antagonist versus the agonist binding was 3.39 (2-5)). SSTR2-immunostaining confirmed SSTR2 expression in the tumor cells. SPECT/MR imaging performed in the mouse model resulted in better tumor visualization with the antagonist. This was in line with the significantly higher tumor uptake of the radiolabeled antagonist versus the agonist measured in the biodistribution studies 285 min post injection of the radiotacers (1.92±0.43 versus 0.90±0.17 % ID/g tissue (P = 0.002), respectively). Conclusion: SSTR antagonists are promising candidates for BC imaging.
- Autoradiography
- Animal Imaging
- Oncology: Breast
- Breast cancer
- Imaging
- Somatostatin receptor
- agonist
- antagonists
- Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.