Fig 1.
18F-FBnTP Uptake in Interscapular Brown Fat Depots at Room Temperature.
Coregistered PET/CT images in transverse (upper panel), coronal (mid panel) and sagittal (lower panel) view, acquired in a rat at room temperature. PET images represent summed activity acquired over the 10 to 30 min time interval after 18F-FBnTP administration. 18F-FBnTP increased uptake in the interscapular area is confined to CT regions of low Hounsfield units (black arrows). Note the strong uptake of 18F-FBnTP in BAT, similar to that seen in heart (blue arrow).
Fig 2.
18F-FBnTP Uptake Kinetics and Selectivity to BAT at Rest.
18F-FBnTP PET images acquired in same animal before (A—C) and after surgical excision of BAT (D), and related time-activity curves (E—F). Note the lack of uptake in the interscapular area after BAT excision (D). Images in (A to C) and (D) represent PET scans acquired in the same animal at an interval of 12 min. Chart in (E) represents 18F-FBnTP time activity curve generated from the same animal in (A to C). Chart in (F) is zooming of the first 240 sec in (E). Y-axis in (F) has same unit value and scale as in (E). Note the strong 18F-FBnTP uptake in BAT, which is similar to that in the heart, and 8 times greater than background activity (E). 18F-FBnTP reaches plateau concentration in BAT within less than a minute (F).
Fig 3.
Cold-induced Mitochondrial Uncoupling Elicits an Immediate 18F-FBnTP Washout from BAT.
(A) Coronal PET/CT images of BAT acquired at room temperature. (B) 18F-FBnTP PET images of BAT before and during cold stimulation. Images are segmented using max50% cutoff value. Each image represents summed activity over 3 min. Beginning of acquisition time of each frame is indicated in upper right corner. Cold stimulation started at the 30 min point of the scan. (C) 18F-FBnTP time activity curve generated from same animal depicted in (B). (D) 18F-FBnTP mean uptake measured on 10-min image frame, acquired just before (baseline) and 20 and 50 min after the start of cold stimulation (mean±SD, n = 6). Note the immediate sharp decrease of 18F-FBnTP uptake upon application of cold stimulation (B and C), and small, but insignificant washout at later time points (D), as well as lack of effect on uptake in heart (D).
Fig 4.
18F-FBnTP Washout Response Precedes Change in Body Core Temperature.
Colonic temperature (A) and 18F-FBnTP uptake kinetics (B) monitored in same animal before and during skin cooling. (C) Mean change in colonic temperature induced by cold stimulation (mean±SD, n = 6). (D) Extent of 18F-FBnTP washout response correlated with colonic temperature (n = 6). Note the sharp washout of 18F-FBnTP, which nearly completed before significant change in colonic temperature was attained (D).
Fig 5.
Noradrenergic Mediation of 18F-FBnTP Washout Response.
(A) Effect of propranolol 18F-FBnTP-washout response to cold stimulation. Propranolol blocked cold-induced 18F-FBnTP washout from BAT. A slight but insignificant decrease (9.6%±11.6%; P<0.21) was measured. (B) Effect of the ß3-AR agonist CL-316,243 on 18F-FBnTP retention in BAT. Administration of CL-316,243 (100 μg, IV) resulted in 18F-FBnTP washout from BAT with kinetics similar to those observed during cold stimulation. (C) 18F-FBnTP PET imaged of BAT before and after administration of CL-316,243. Both PET images in (C) and time activity curve in (B) were taken form same rat’s BAT. Note the CL-316,243-induced washout kinetics, which are similar to those observed during localized skin cooling. (D) CL-316,243 hardly affected 18F-FBnTP retention in heart muscle.