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

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.

Gastrin releasing peptide receptor targeted nano-graphene oxide for near-infrared fluorescence imaging of oral squamous cell carcinoma

“…Actively targeting tumors with cancer-specific molecules containing fluorescent groups plays an important role in the diagnosis and treatment of OSCC. In recent years, GRPR has been used as a target for cancer diagnosis and treatment of prostate cancer, breast cancer and small cell lung cancer 30 – 32 . Few studies were conducted to investigate the GRPR targeting potential in human head and neck squamous cell carcinoma OSCC.…”

Design, synthesis and evaluation of PD176252 analogues for ameliorating cisplatin-induced nephrotoxicity

“…Thus, they can be used as important markers for the diagnosis of renal toxicity in vitro and in vivo. [17][18][19] Bombesin/gastrin-releasing peptide receptor (GRPR), [20][21][22][23] which is a G protein-coupled receptor, 24 is involved in the regulation of the release of inflammatory factors and plays a role in inflammatory diseases. 22,25 In recent studies, GRPR inhibitors have been known to ameliorate some diseases by inhibiting the inflammatory response.…”

Recent Advances in Nuclear Imaging of Receptor Expression to Guide Targeted Therapies in Breast Cancer

“…Interesting studies evaluated a novel radiolabeled GRPR antagonist, NeoBOMB1, radiolabeled with [ 67 / 68 Ga/ 111 In/ 177 Lu] as a theranostic tool in a prostate cancer animal model [132] and in prostate cancer patients [133]. Recently, on the basis of these observations, the same authors investigated the potential of this molecule as an agent for imaging and therapy of GRPR-positive mammary carcinoma and reported the ability of [ 67 Ga]NeoBOMB1 to specifically localize in the tumors of mice bearing T-47D breast xenografts [77].…”