Molecular MR-Imaging for Noninvasive Quantification of the Anti-Inflammatory Effect of Targeting Interleukin-1β in a Mouse Model of Aortic Aneurysm,Molecular Imaging

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Molecular MR-Imaging for Noninvasive Quantification of the Anti-Inflammatory Effect of Targeting Interleukin-1β in a Mouse Model of Aortic Aneurysm
Molecular Imaging ( IF 2.8 ) Pub Date : 2020-11-20 , DOI: 10.1177/1536012120961875
Julia Brangsch _{1,

2} , Carolin Reimann _{1,

2} , Jan Ole Kaufmann _{1,

3,

4} , Lisa Christine Adams ₁ , David Onthank ₅ , Christa Thöne-Reineke ₂ , Simon Robinson ₅ , Marco Wilke ₃ , Michael Weller ₃ , Rebecca Buchholz ₆ , Uwe Karst ₆ , Rene Botnar _{7,

8,

9,

10} , Bernd Hamm ₁ , Marcus Richard Makowski _{1,

7,

9,

11}

Affiliation

Department of Radiology, 14903Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.
Department of Veterinary Medicine, Institute of Animal Welfare, Animal Behavior and Laboratory Animal Science, Freie Universität Berlin, Berlin, Germany.
Division 1.5 Protein Analysis, Federal Institute for Materials Research and Testing (BAM), Berlin, Germany.
Department of Chemistry, Humboldt-Universität zu Berlin, Berlin, Germany.
128865Lantheus Medical Imaging, North Billerica, MA, USA.
Institute of Inorganic and Analytical Chemistry, 9185Westfälische Wilhelms-Universität Münster, Münster, Germany.
School of Biomedical Engineering and Imaging Sciences, 4616King's College London, St Thomas' Hospital, London, United Kingdom.
Wellcome Trust/EPSRC Centre for Medical Engineering, 4616King's College London, United Kingdom.
BHF Centre of Excellence, 4616King's College London, Denmark Hill Campus, London, United Kingdom.
Escuela de Ingeniería, Pontificia Universidad Católica de Chile, Santiago, Chile.
Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.

Background:

Molecular-MRI is a promising imaging modality for the assessment of abdominal aortic aneurysms (AAAs). Interleukin-1β (IL-1β) represents a new therapeutic tool for AAA-treatment, since pro-inflammatory cytokines are key-mediators of inflammation. This study investigates the potential of molecular-MRI to evaluate therapeutic effects of an anti-IL-1β-therapy on AAA-formation in a mouse-model.

Methods:

Osmotic-minipumps were implanted in apolipoprotein-deficient-mice (N = 27). One group (Ang-II+01BSUR group, n = 9) was infused with angiotensin-II (Ang-II) for 4 weeks and received an anti-murine IL-1β-antibody (01BSUR) 3 times. One group (Ang-II-group, n = 9) was infused with Ang-II for 4 weeks but received no treatment. Control-group (n = 9) was infused with saline and received no treatment. MR-imaging was performed using an elastin-specific gadolinium-based-probe (0.2 mmol/kg).

Results:

Mice of the Ang-II+01BSUR-group showed a lower aortic-diameter compared to mice of the Ang-II-group and control mice (p < 0.05). Using the elastin-specific-probe, a significant decrease in elastin-destruction was observed in mice of the Ang-II+01BSUR-group. In vivo MR-measurements correlated well with histopathology (y = 0.34x-13.81, R² = 0.84, p < 0.05), ICP-MS (y = 0.02x+2.39; R² = 0.81, p < 0.05) and LA-ICP-MS. Immunofluorescence and western-blotting confirmed a reduced IL-1β-expression.

Conclusions:

Molecular-MRI enables the early visualization and quantification of the anti-inflammatory-effects of an IL-1β-inhibitor in a mouse-model of AAAs. Responders and non-responders could be identified early after the initiation of the therapy using molecular-MRI.

中文翻译：

分子 MR 成像对主动脉瘤小鼠模型中靶向 IL-1β 的抗炎作用的无创定量

背景：

分子磁共振成像是评估腹主动脉瘤 (AAA) 的一种很有前途的成像方式。白细胞介素 1β (IL-1β) 代表了一种新的 AAA 治疗工具，因为促炎细胞因子是炎症的关键介质。本研究调查了分子 MRI 评估抗 IL-1β 疗法对小鼠模型中 AAA 形成的治疗效果的潜力。

方法：

将渗透性微型泵植入载脂蛋白缺陷小鼠（N = 27）。一组（Ang-II+01BSUR 组，n = 9）输注血管紧张素-II（Ang-II）4 周，并接受抗鼠 IL-1β-抗体（01BSUR）3 次。一组（Ang-II 组，n = 9）被注入 Ang-II 4 周，但未接受任何治疗。对照组（n = 9）输注生理盐水，未接受任何治疗。使用弹性蛋白特异性钆基探针 (0.2 mmol/kg) 进行 MR 成像。

结果：

与 Ang-II 组小鼠和对照小鼠相比，Ang-II+01BSUR 组小鼠的主动脉直径较低 (p < 0.05)。使用弹性蛋白特异性探针，在 Ang-II+01BSUR 组的小鼠中观察到弹性蛋白破坏显着减少。体内 MR 测量与组织病理学 (y = 0.34x-13.81, R ² = 0.84, p < 0.05)、ICP-MS (y = 0.02x+2.39; R ² = 0.81, p < 0.05) 和 LA- ICP-MS。免疫荧光和蛋白质印迹证实了 IL-1β 表达降低。