TY - JOUR T1 - [<sup>18</sup>F]FDG-PET/MR Imaging of Brown and Beige Adipose Tissues in Preclinical Model JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1015 LP - 1015 VL - 62 IS - supplement 1 AU - Kel Tan AU - Qing Liu AU - Xiaoyan Hui AU - Hing-Chiu Chang AU - Pek-Lan Khong Y1 - 2021/05/01 UR - http://jnm.snmjournals.org/content/62/supplement_1/1015.abstract N2 - 1015Objectives: Brown and beige adipocytes are now recognized as new therapeutic targets for obesity due to fat-reducing effect. Upon cold stimulation or direct β-adrenergic activation, white adipose tissues (WAT) undergo browning to recruit beige adipocytes that share similar thermogenic capacities as brown adipose tissues (BAT). Non-invasive imaging of BAT and WAT activation provides a better understanding of the molecular control of these adipocytes. In this work, we investigate the feasibility of [18F]FDG uptake as a reliable imaging biomarker to monitor the process of BAT activation and WAT browning after stimulation by prolonged cold exposure or β3-adrenergic receptor agonist in a mouse model. Methods: A total of 12 C57BL/6 mice (6 - 8 weeks old, male) were randomly assigned into four treatment groups in this study: (i) Control (CO), (ii) β3-agonist CL316,243 injection (CI), (iii) Cold exposure (CE), (iv) Cold exposure after interscapular BAT (iBAT) removal (CEx). Both CE and CEx mice underwent a midline incision, where the bilateral iBAT pads were removed only in the CEx group. Mice were given normal chow and housed at thermoneutrality (30 °C) for 21 days, except that for CE and CEx mice were housed at 6 °C in the environmental chamber on day 14 for one week. CI mice underwent overnight fasting and were given single dose of CL316,243 (1 mg/kg) intraperitoneally 1 hour before [18F]FDG administration on the imaging day. Mice received 200 - 250 μCi [18F]FDG via lateral tail vein and maintained in their housing conditions for 1 hour before PET/MR imaging. Regions of interest (ROI) were drawn in the iBAT and inguinal WAT (iWAT) on the co-registered PET/MR images, avoiding neighboring organs. Circular ROI were placed in the left lung as background activity. Data were presented as mean standard uptake value and target-to-background ratios (SUVratio) as indices of [18F]FDG uptake. Results: PET/MR showed low [18F]FDG uptake in the iBAT and iWAT at baseline (CO). Prolonged cold exposure (CE) resulted in a markedly elevated [18F]FDG uptake on iBAT (6.7-fold, p&lt;0.0001) but only a modest increase on iWAT (2.5-fold). Removal of iBAT (CEx) caused a significantly higher [18F]FDG uptake in iWAT (8.5-fold, p&lt;0.01) that can be readily visualized on PET. Pharmacological stimulation with CL316,243 also revealed a greater [18F]FDG uptake in both iBAT and iWAT although fasting is required. Hematoxylin and Eosin staining of iWAT demonstrated a more pronounced multilocular adipocytes for CEx mice, which are the characteristic morphology for beige adipocytes. Representative images and results are shown in Figure 1. Conclusions: [18F]FDG-PET/MR is a promising tool to monitor the activity of brown and beige adipocytes in vivo. [18F]FDG uptake can potentially serve as an imaging biomarker to study the process of WAT thermogenesis, thus to promote the development of new drugs and screening efficacy of strategies to treat obesity. Acknowledgements: This study was supported by the Hong Kong Research Grants Council Collaborative Research Fund (CRF C7018-14E) and General Research Fund (GRF 17123419). Figure 1: Representative in vivo [18F]FDG uptake in iBAT and iWAT. PET/MR images of (A) sagittal view showing iBAT, (B) axial view showing bilateral iWAT in mice. (C) Quantitative analysis of uptake in iBAT (right top) and iWAT (right bottom). Yellow arrows: iBAT. White arrows: iWAT. n = 3 for each group. Values of SUVratio are presented as mean ± SD. *p &lt;0.05, **p &lt; 0.0001. ER -