The Study On The Establishing And Relative Application Of Evaluation System Of Bat Using Micro-PET/CT

Brown adipose tissue (BAT) is a new fat type which is only found inmammals. It was named because of its brownish color resulting fromincreased mitochondrial content and rich vascularization. Different fromwhite fat, BAT is proved to play important role in non-shiveringthermogenesis and diet-induced thermogenesis. Recent reports indicated thatBAT might have important roles in regulating energy balance and thereforemay be of significance for the treatments of energy metabolism relateddiseases such as obesity, diabetes and metabolic disorders. Thecharacterization and modulation of BAT and its activities has attracted greatinterests recently.As an excellent in vivo metabolic imaging technology, FDG-PET hasshown sensitive and important on BAT quality and quantity evaluation.However, BAT is related to energy metabolism, regulated by the sympatheticnervous system and thyroid hormones. Many factors would affect theactivity of BAT, which would change the FDG uptake and influence the experimental result. So far, the specific effect of these factors has notvalidated and the standard imaging protocols for BAT18F-FDG PET/CTstudies have not established, which will significantly influence the qualityand quantity evaluation of BAT.In order for a stable microPET/CT scan protocol of BAT activity assay,we systematically study the effect of influence factors, such as injectionmethod, environmental adaptation, comfortable dealing, anesthesia,temperature interference and stress, on BAT18F-FDG uptake, and found thatthese factor have significantly effect on the activity, visualization andstability of BAT. We established a standard protocol and gave somesuggestions for BAT microPET/CT evaluation through the summarizing ofthese factors.To examine the effect of outdoor temperature and dietary states on theamount and activity of BAT, we evaluated these two factors withmicroPET/CT according to the protocol we designed before and found theywould significantly influence the activity of BAT. With the increase ofoutdoor temperature, the BAT signals diminished significantly and can’t bewell visualized in the PET image in the warm days. In the dietaryintervention study, the FDG uptake in the BAT increased after giving food,reached its peak at4h. The18F-FDG uptake of BAT in the1h group, whichshowed the best visualize effect, was relatively stable. The RT-PCR result of UCP1, which is uniquely expressed in BAT has confirmed this conclusion.Considering that BAT can’t be activated by cold in non-fasted mice and can’tbe well visualized in the PET image in the warm days, we optimized thescan protocol by food intervention and suggested that food should be givenfor0.5hours1h before FDG injection. Our optimization markedly improvedthe visualization, activation and stability of BAT in PET/CT studies.Based on the above results, we established a standard protocol for BATmicroPET/CT evaluation: The mice were taken to the temperate housingroom next to the microPET/CT room one day before the scan and getaccustomed to the environment with a constant room temperature of22℃.Food was given ad libitum for0.5hours after18hours’ fasting and takenaway afterwards. The mice were again fasted for1h before FDG injection.They were moved to a thermoneutral chamber (30℃) and accustomed for0.5h before FDG administration. Each mouse got an injection of120-140μCiof18F-FDG without anesthesia. They were allowed for1hour of uptakephase and then scanned under isoflurane anesthesia: CT scan for10min, PETscan for5min. After that we use a compound CL316,243which was reportedto stimulate the activity of BAT for the test and verify of our scanningprotocol. The significant activation effect and does effect of our resultconfirmed the feasibility of the protocol. Then we evaluate the effect of anew compound FL-001, which was designed for the cytochrome C in the respiratory chain, on the accumulation of18F-FDG in BAT and proved itsactivation effect. At last, we evaluated the effect of BAT activity to the tumorimaging and showed that the increase of BAT FDG uptake will significantlydecrease the FDG uptake of tumor.