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Molecules 2017, 22(11), 1950; doi:10.3390/molecules22111950

NeoBOMB1, a GRPR-Antagonist for Breast Cancer Theragnostics: First Results of a Preclinical Study with [67Ga]NeoBOMB1 in T-47D Cells and Tumor-Bearing Mice

1
Molecular Radiopharmacy, INRASTES/NCSR “Demokritos”, 15310 Athens, Greece
2
Department of Radiology, Erasmus MC, 3015 CN Rotterdam, The Netherlands
3
Advanced Accelerator Applications, 10010 Colleretto Giacosa TO, Italy
*
Author to whom correspondence should be addressed.
Received: 26 October 2017 / Revised: 6 November 2017 / Accepted: 8 November 2017 / Published: 11 November 2017
(This article belongs to the Special Issue Peptide Therapeutics)
View Full-Text   |   Download PDF [2661 KB, uploaded 11 November 2017]   |  

Abstract

Background: The GRPR-antagonist-based radioligands [67/68Ga/111In/177Lu]NeoBOMB1 have shown excellent theragnostic profiles in preclinical prostate cancer models, while [68Ga]NeoBOMB1 effectively visualized prostate cancer lesions in patients. We were further interested to explore the theragnostic potential of NeoBOMB1 in GRPR-positive mammary carcinoma, by first studying [67Ga]NeoBOMB1 in breast cancer models; Methods: We investigated the profile of [67Ga]NeoBOMB1, a [68Ga]NeoBOMB1 surrogate, in GRPR-expressing T-47D cells and animal models; Results: NeoBOMB1 (IC50s of 2.2 ± 0.2 nM) and [natGa]NeoBOMB1 (IC50s of 2.5 ± 0.2 nM) exhibited high affinity for the GRPR. At 37 °C [67Ga]NeoBOMB1 strongly bound to the T-47D cell-membrane (45.8 ± 0.4% at 2 h), internalizing poorly, as was expected for a radioantagonist. [67Ga]NeoBOMB1 was detected >90% intact in peripheral mouse blood at 30 min pi. In mice bearing T-47D xenografts, [67Ga]NeoBOMB1 specifically localized in the tumor (8.68 ± 2.9% ID/g vs. 0.6 ± 0.1% ID/g during GRPR-blockade at 4 h pi). The unfavorably high pancreatic uptake could be considerably reduced (206.29 ± 17.35% ID/g to 42.46 ± 1.31% ID/g at 4 h pi) by increasing the NeoBOMB1 dose from 10 pmol to 200 pmol, whereas tumor uptake remained unaffected. Notably, tumor values did not decline from 1 to 24 h pi; Conclusions: [67Ga]NeoBOMB1 can successfully target GRPR-positive breast cancer in animals with excellent prospects for clinical translation. View Full-Text
Keywords: GRPR-antagonist; theragnostics; targeted tumor imaging; PET-imaging; breast cancer GRPR-antagonist; theragnostics; targeted tumor imaging; PET-imaging; breast cancer
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Kaloudi, A.; Lymperis, E.; Giarika, A.; Dalm, S.; Orlandi, F.; Barbato, D.; Tedesco, M.; Maina, T.; de Jong, M.; Nock, B.A. NeoBOMB1, a GRPR-Antagonist for Breast Cancer Theragnostics: First Results of a Preclinical Study with [67Ga]NeoBOMB1 in T-47D Cells and Tumor-Bearing Mice. Molecules 2017, 22, 1950.

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