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创新型[18F]标记放射性示踪剂[18F]-BIBD-071在HR+乳腺癌异种移植小鼠模型中的应用。

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

作者信息

Fan Di, Wang Xin, Ling Xueyuan, Li Hongbin, Zhang Lu, Zheng Wei, Wu Zehui, Ai Lin

机构信息

Department of Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China.

出版信息

Pharmaceuticals (Basel). 2025 Jan 9;18(1):66. doi: 10.3390/ph18010066.

Abstract

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. [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. [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 ( < 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. [18F]BIBD-071 is a promising PET tracer for diagnosing and monitoring HR+ breast cancer, warranting further research into hormone-dependent cancers.

摘要

芳香化酶在雄激素向雌激素的转化过程中起关键作用,且在激素依赖性肿瘤,尤其是乳腺癌中常过度表达。[18F]BIBD - 071对芳香化酶具有出色的结合亲和力和良好的药代动力学,具有诊断和治疗芳香化酶相关疾病的潜力。采用激素受体阳性(HR +)的MCF - 7细胞系,通过HR +乳腺癌异种移植模型的正电子发射断层扫描(PET)成像,对新型[18F]标记的放射性示踪剂[18F]BIBD - 071进行评估。合成并放射性标记了[18F]BIBD - 071,然后进行体外稳定性测试。培养MCF - 7细胞并将其植入BALB/c裸鼠体内以建立皮下肿瘤模型。在注射示踪剂后1小时和2小时进行MicroPET/CT成像,同时使用芳香化酶抑制剂来曲唑进行阻断研究。采用阻断实验来证明探针的特异性。在注射后0.5小时、1小时和2小时进行生物分布研究。使用免疫荧光法评估MCF - 7细胞中芳香化酶的表达。[18F]BIBD - 071在MCF - 7异种移植肿瘤模型中表现出出色的体外稳定性和特异性摄取。注射后1小时和2小时的MicroPET/CT成像显示肿瘤可视化效果极佳,肿瘤与背景比值良好。生物分布数据显示,示踪剂在肝脏、小肠和胃中摄取较高,随着时间推移,血液和肿瘤中的示踪剂显著清除。0.5小时、1小时和2小时的肿瘤摄取量分别为3.84±0.13、2.5±0.17和2.54±0.32。0.5小时至1小时之间肿瘤摄取量显著下降(<0.0001),而1小时至2小时之间无显著差异。0.5小时、1小时和2小时的肿瘤/背景比值分别为1.19±0.03、1.12±0.17和1.42±0.11。免疫荧光证实MCF - 7细胞中芳香化酶表达强烈,这与[18F]BIBD - 071的肿瘤摄取相关。[18F]BIBD - 071是一种有前景的用于诊断和监测HR +乳腺癌的PET示踪剂,值得对激素依赖性癌症进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b7a/11768299/c61c337260c8/pharmaceuticals-18-00066-g001.jpg

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