Synthesis, radiosynthesis and in vitro evaluation of 18F-Bodipy-C16/triglyceride as a dual modal imaging agent for brown adipose tissue

Andreas Paulus*, Marco Maenen, Natascha Drude, Emmani B. M. Nascimento, Wouter D. van Marken Lichtenbelt, Felix M. Mottaghy, Matthias Bauwens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Web of Science)

Abstract

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 F-18 using an F-18/F-19 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.

Original languageEnglish
Article number0182297
Number of pages13
JournalPLOS ONE
Volume12
Issue number8
DOIs
Publication statusPublished - 17 Aug 2017

Keywords

  • FATTY-ACID UPTAKE
  • POSITRON-EMISSION-TOMOGRAPHY
  • MAGNETIC-RESONANCE
  • ADULT HUMANS
  • LIPOPROTEIN-LIPASE
  • COLD-EXPOSURE
  • BODIPY DYES
  • TRANSPORT
  • METABOLISM
  • ADIPOCYTES

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