Paulus Andreas, Maenen Marco, Drude Natascha, Nascimento Emmani B M, van Marken Lichtenbelt Wouter D, Mottaghy Felix M, Bauwens Matthias
Department of Radiology and Nuclear Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
Department of Medical Imaging, Division of Nuclear Medicine, MUMC, Maastricht, The Netherlands.
PLoS One. 2017 Aug 17;12(8):e0182297. doi: 10.1371/journal.pone.0182297. eCollection 2017.
Brown adipose tissue research is in the focus in the field of endocrinology. We designed a dual-modal fluorescent/PET fatty acid based tracer on commercially available Bodipy-C16, which can be synthesized to its corresponding triglyceride and which combines the benefits of fluorescent and PET imaging.
Bodipy-C16 was coupled to 1,3-diolein resulting in Bodipy-triglyceride. Bodipy-C16 and Bodipy-triglyceride compounds were radiolabeled with 18F using an 18F/19F exchange reaction to yield a dual-modal imaging molecule. Uptake of radiolabeled and non-labeled Bodipy-C16 and Bodipy-triglyceride was analyzed by fluorescence imaging and radioactive uptake in cultured adipocytes derived from human brown adipose tissue and white adipose tissue.
Bodipy-C16 and Bodipy-triglyceride were successfully radiolabeled and Bodipy-C16 showed high shelf life and blood plasma stability (99% from 0-4 h). The uptake of Bodipy-C16 increased over time in cultured adipocytes, which was further enhanced after beta-adrenergic stimulation with norepinephrine. The uptake of Bodipy-C16 was inhibited by oleic acid and CD36 inhibitor sulfosuccinimidyl-oleate. The poor solubility of Bodipy-triglyceride did not allow stability or in vitro experiments.
The new developed dual modal fatty acid based tracers Bodipy-C16 and Bodipy-triglyceride showed promising results to stimulate further in vivo evaluation and will help to understand brown adipose tissues role in whole body energy expenditure.
棕色脂肪组织研究是内分泌学领域的焦点。我们基于市售的Bodipy-C16设计了一种双模态荧光/PET脂肪酸示踪剂，它可以合成其相应的甘油三酯，并结合了荧光成像和PET成像的优点。
将Bodipy-C16与1,3-二油精偶联，得到Bodipy-甘油三酯。使用18F/19F交换反应将Bodipy-C16和Bodipy-甘油三酯化合物用18F进行放射性标记，以产生双模态成像分子。通过荧光成像和放射性摄取分析来自人棕色脂肪组织和白色脂肪组织的培养脂肪细胞中放射性标记和未标记的Bodipy-C16及Bodipy-甘油三酯的摄取情况。
Bodipy-C16和Bodipy-甘油三酯成功进行了放射性标记，且Bodipy-C16显示出高保质期和血浆稳定性（0 - 4小时内为99%）。在培养的脂肪细胞中，Bodipy-C16的摄取随时间增加，在用去甲肾上腺素进行β-肾上腺素能刺激后进一步增强。Bodipy-C16的摄取受到油酸和CD36抑制剂磺基琥珀酰亚胺油酸酯的抑制。Bodipy-甘油三酯的溶解性差，无法进行稳定性或体外实验。
新开发的基于脂肪酸的双模态示踪剂Bodipy-C16和Bodipy-甘油三酯显示出有前景的结果，可刺激进一步的体内评估，并将有助于了解棕色脂肪组织在全身能量消耗中的作用。
