In Vivo Optical Imaging of Interscapular Brown Adipose Tissue with 18F-FDG via Cerenkov Luminescence Imaging

Xueli Zhang,Anna Moore,Chongzhao Ran,Chaincy Kuo,Juri G Gelovani

doi:10.1371/journal.pone.0062007

Abstract

ObjectiveBrown adipose tissue (BAT), a specialized tissue for thermogenesis, plays important roles for metabolism and energy expenditure. Recent studies validated BAT’s presence in human adults, making it an important re-emerging target for various pathologies. During this validation, PET images with 18F-FDG showed significant uptake of 18F-FDG by BAT under certain conditions. Here, we demonstrated that Cerenkov luminescence imaging (CLI) using 18F-FDG could be utilized for in vivo optical imaging of BAT in mice.MethodsMice were injected with 18F-FDG and imaged 60 minutes later with open filter and 2 minute acquisition. In vivo activation of BAT was performed by norepinephrine and cold treatment under isoflurane or ketamine anesthesia. Spectral unmixing and 3D imaging reconstruction were conducted with multiple-filter CLI images.Results1) It was feasible to use CLI with 18F-FDG to image interscapular BAT in mice, with the majority of the signal (>85%) at the interscapular site originating from BAT; 2) The method was reliable because excellent correlations between in vivo CLI, ex vivo CLI, and ex vivo radioactivity were observed; 3) CLI could be used for monitoring BAT activation under different conditions; 4) CLI signals from the group under short-term isoflurane anesthesia were significantly higher than that from the group under long-term anesthesia; 5) The CLI spectrum of 18F-FDG with a peak at 640 nm in BAT after spectral unmixing reflected the actual context of BAT; 6) Finally 3D reconstruction images showed excellent correlation between the source of the light signal and the location and physical shape of BAT.ConclusionCLI with 18F-FDG is a feasible and reliable method for imaging BAT in mice. Compared to PET imaging, CLI is significantly cheaper, faster for 2D planar imaging and easier to use. We believe that this method could be used as an important tool for researchers investigating BAT.

Highlights

Brown adipose tissue (BAT) is a specialized tissue for thermogenesis in mammals, and it has been considered as a furnace in the body for burning excess calories
Multiple studies have demonstrated that BAT mass levels inversely correlate with body-mass index (BMI), and that physical exercises could increase BAT mass, suggesting that BAT may play important roles in obesity and diabetes [7,8,15,16,17]
Cerenkov luminescence imaging (CLI) Feasibility for BAT Imaging To test whether CLI with 18F-FDG is capable of providing significant signal and contrast, 10.3 MBq of 18F-FDG was intravenously injected into nude mice

Summary

Introduction

Brown adipose tissue (BAT) is a specialized tissue for thermogenesis in mammals, and it has been considered as a furnace in the body for burning excess calories. The function of BAT in mammals is to dissipate large amounts of chemical/food energy as heat, maintaining the energy balance of the whole body [1,2,3]. It has been considered that BAT disappears from the body of adults and has no significant physiological relevance in adult humans [1,4,5,6]. BAT has emerged as an important target for various other diseases such as neurodegenerative disease and cancer [5,9,10,11,12]. The ability to image BAT noninvasively would aid in clinical staging of various diseases as well as in drug development processes

Results

Discussion

Conclusion