Open AccessSynthesis, radiosynthesis and in vitro evaluation of 18F-Bodipy-C16/triglyceride as a dual modal imaging agent for brown adipose tissue
Author(s) -
Andreas Paulus,
Marco Maenen,
Natascha Drude,
Emmani B. M. Nascimento,
Wouter D. van Marken Lichtenbelt,
Felix M. Mottaghy,
Matthias Bauwens
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0182297
Subject(s) - bodipy , triglyceride , adipose tissue , chemistry , biochemistry , fatty acid , oleic acid , in vivo , biophysics , fluorescence , cholesterol , biology , physics , quantum mechanics , microbiology and biotechnology
Background 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-C 16 , which can be synthesized to its corresponding triglyceride and which combines the benefits of fluorescent and PET imaging. Methods Bodipy-C 16 was coupled to 1,3-diolein resulting in Bodipy-triglyceride. Bodipy-C 16 and Bodipy-triglyceride compounds were radiolabeled with 18 F using an 18 F/ 19 F exchange reaction to yield a dual-modal imaging molecule. Uptake of radiolabeled and non-labeled Bodipy-C 16 and Bodipy-triglyceride was analyzed by fluorescence imaging and radioactive uptake in cultured adipocytes derived from human brown adipose tissue and white adipose tissue. Results Bodipy-C 16 and Bodipy-triglyceride were successfully radiolabeled and Bodipy-C 16 showed high shelf life and blood plasma stability (99% from 0–4 h). The uptake of Bodipy-C 16 increased over time in cultured adipocytes, which was further enhanced after beta-adrenergic stimulation with norepinephrine. The uptake of Bodipy-C 16 was inhibited by oleic acid and CD36 inhibitor sulfosuccinimidyl-oleate. The poor solubility of Bodipy-triglyceride did not allow stability or in vitro experiments. Conclusion The new developed dual modal fatty acid based tracers Bodipy-C 16 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.