Utilisation of the Innovative [18F]-Labelled Radiotracer [18F]-BIBD-071 Within HR+ Breast Cancer Xenograft Mouse Models

Abstract

Background/Objectives: Aromatase plays a crucial role in the conversion of androgens to oestrogens and is often overexpressed in hormone-dependent tumours, particularly breast cancer. [18F]BIBD-071, which has excellent binding affinity for aromatase and good pharmacokinetics, has potential for the diagnosis and treatment of aromatase-related diseases. The MCF-7 cell line, which is hormone receptor-positive (HR+), was used in the assessment of the novel [18F]-labelled radiotracer [18F]BIBD-071 via positron emission tomography (PET) imaging of an HR+ breast cancer xenograft model. Methods: [18F]BIBD-071 was synthesised, radiolabelled, and then subjected to in vitro stability testing. MCF-7 cells were cultured and implanted into BALB/c nude mice to establish subcutaneous tumour models. MicroPET/CT imaging was conducted after injection of the tracer at 1 and 2 h, and a blocking study was also conducted using the aromatase inhibitor letrozole. A block experiment was used to prove the specificity of the probe. Biodistribution studies were performed at 0.5, 1, and 2 h post injection (p.i.). Immunofluorescence was used to assess aromatase expression in MCF-7 cells. Results: [18F]BIBD-071 showed excellent in vitro stability and specific uptake in an MCF-7 xenograft tumour model. MicroPET/CT imaging at 1 and 2 h p.i. revealed excellent tumour visualisation with a favourable tumour-to-background ratio. Biodistribution data revealed high tracer uptake in the liver, small intestine, and stomach, with significant washout from the bloodstream and tumour over time. The tumour uptakes at 0.5 h, 1 h, and 2 h were 3.84 ± 0.13, 2.5 ± 0.17, and 2.54 ± 0.32, respectively. The tumour uptake significantly decreased between 0.5 h and 1 h (p < 0.0001), whereas there was no significant difference between 1 and 2 h. The tumour/background ratios at 0.5 h, 1 h, and 2 h were 1.19 ± 0.03, 1.12 ± 0.17, and 1.42 ± 0.11, respectively. Immunofluorescence confirmed robust aromatase expression in MCF-7 cells, which was correlated with [18F]BIBD-071 tumour uptake. Conclusions: [18F]BIBD-071 is a promising PET tracer for diagnosing and monitoring HR+ breast cancer, warranting further research into hormone-dependent cancers.

Keywords: HR+ breast cancer; PET/CT; [18F]BIBD-071; aromatase.

Figure 1

Radioactive HPLC profile of [18F]BIBD-071 (A). Radioactive HPLC profile of [18F]BIBD-071 following incubation in PBS or FBS for 60 min (B,C) and 120 min (D,E). Structural diagram of [18F]BIBD-071 (F).

Figure 2

Representative small animal PET images of [18F]BIBD-071 in an MCF-7 xenograft breast tumour model with/without the blocking agent letorzole. The arrows indicate the breast tumour.

Figure 3

(A) Biodistribution of [18F]BIBD-071 in BALB/c nude mice across various organs, with the periods of 0.5, 1, and 2 h as the optimal time frames. (B) Tumour uptake at 0.5, 1 and 2 h. (***: p < 0.0001) (n = 3).

Figure 4

Fluorescence visualisation of the binding between the CYP19A1 polyclonal antibody and MCF-7 cells, as visualised via ortho-fluorescence microscopy. The scale bar equals 50 µm.